Antioxidants

21 pages, 6951 KiB

Open AccessArticle

Screening and Mechanism Study of Three Antagonistic Drugs, Oxysophoridine, Rutin, and Phellodendrine, against Zearalenone-Induced Reproductive Toxicity in Ovine Oocytes

by Zongshuai Li, Tian Ma, Yali Liu, Wanruo Liu, Xingxu Zhao, Gaiping Zhang, Jianlin Wang and Yong Zhang

Antioxidants 2024, 13(6), 752; https://doi.org/10.3390/antiox13060752 - 20 Jun 2024

Viewed by 1052

Abstract

Zearalenone (ZEN) is a common fungal toxin with reproductive toxicity in various grains. It poses a serious threat to ovine and other animal husbandry industries, as well as human reproductive health. Therefore, investigating the mechanism of toxicity and screening antagonistic drugs are of [...] Read more.

Zearalenone (ZEN) is a common fungal toxin with reproductive toxicity in various grains. It poses a serious threat to ovine and other animal husbandry industries, as well as human reproductive health. Therefore, investigating the mechanism of toxicity and screening antagonistic drugs are of great importance. In this study, based on the natural compound library and previous Smart-seq2 results, antioxidant and anti-apoptotic drugs were selected for screening as potential antagonistic drugs. Three natural plant compounds (oxysophoridine, rutin, and phellodendrine) were screened for their ability to counteract the reproductive toxicity of ZEN on ovine oocytes in vitro using quantitative polymerase chain reaction (qPCR) and reactive oxygen species detection. The compounds exhibited varying pharmacological effects, notably impacting the expression of antioxidant (GPX, SOD1, and SOD2), autophagic (ATG3, ULK2, and LC3), and apoptotic (CAS3, CAS8, and CAS9) genes. Oxysophoridine promoted GPX, SOD1, ULK2, and LC3 expression, while inhibiting CAS3 and CAS8 expression. Rutin promoted SOD2 and ATG3 expression, and inhibited CAS3 and CAS9 expression. Phellodendrine promoted SOD2 and ATG3 expression, and inhibited CAS9 expression. However, all compounds promoted the expression of genes related to cell cycle, spindle checkpoint, oocyte maturation, and cumulus expansion factors. Although the three drugs had different regulatory mechanisms in enhancing antioxidant capacity, enhancing autophagy, and inhibiting cell apoptosis, they all maintained a stable intracellular environment and a normal cell cycle, promoted oocyte maturation and release of cumulus expansion factors, and, ultimately, counteracted ZEN reproductive toxicity to promote the in vitro maturation of ovine oocytes. This study identified three drugs that antagonize the reproductive toxicity of ZEN on ovine oocytes, and compared their mechanisms of action, providing data support and a theoretical basis for their subsequent application in the ovine breeding industry, reducing losses in the breeding industry, screening of ZEN reproductive toxicity antagonists and various toxin antagonists, improving the study of ZEN reproductive toxicity mechanisms, and even protection of human reproductive health. Full article

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40 pages, 1552 KiB

Open AccessReview

Potentials of Natural Antioxidants in Reducing Inflammation and Oxidative Stress in Chronic Kidney Disease

by On Ying Angela Lee, Alex Ngai Nick Wong, Ching Yan Ho, Ka Wai Tse, Angela Zaneta Chan, George Pak-Heng Leung, Yiu Wa Kwan and Martin Ho Yin Yeung

Antioxidants 2024, 13(6), 751; https://doi.org/10.3390/antiox13060751 - 20 Jun 2024

Cited by 5 | Viewed by 3284

Abstract

Chronic kidney disease (CKD) presents a substantial global public health challenge, with high morbidity and mortality. CKD patients often experience dyslipidaemia and poor glycaemic control, further exacerbating inflammation and oxidative stress in the kidney. If left untreated, these metabolic symptoms can progress to [...] Read more.

Chronic kidney disease (CKD) presents a substantial global public health challenge, with high morbidity and mortality. CKD patients often experience dyslipidaemia and poor glycaemic control, further exacerbating inflammation and oxidative stress in the kidney. If left untreated, these metabolic symptoms can progress to end-stage renal disease, necessitating long-term dialysis or kidney transplantation. Alleviating inflammation responses has become the standard approach in CKD management. Medications such as statins, metformin, and GLP-1 agonists, initially developed for treating metabolic dysregulation, demonstrate promising renal therapeutic benefits. The rising popularity of herbal remedies and supplements, perceived as natural antioxidants, has spurred investigations into their potential efficacy. Notably, lactoferrin, Boerhaavia diffusa, Amauroderma rugosum, and Ganoderma lucidum are known for their anti-inflammatory and antioxidant properties and may support kidney function preservation. However, the mechanisms underlying the effectiveness of Western medications and herbal remedies in alleviating inflammation and oxidative stress occurring in renal dysfunction are not completely known. This review aims to provide a comprehensive overview of CKD treatment strategies and renal function preservation and critically discusses the existing literature’s limitations whilst offering insight into the potential antioxidant effects of these interventions. This could provide a useful guide for future clinical trials and facilitate the development of effective treatment strategies for kidney functions. Full article

(This article belongs to the Special Issue Oxidative Stress in Renal Health)

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19 pages, 4645 KiB

Open AccessArticle

Uncovering the Role of Selenite and Selenium Nanoparticles (SeNPs) in Adolescent Rat Adipose Tissue beyond Oxidative Balance: Transcriptomic Analysis

by Fátima Nogales, Eloísa Pajuelo, Inés Romero-Herrera, Olimpia Carreras, Francisco Merchán, José A. Carrasco López and María Luisa Ojeda

Antioxidants 2024, 13(6), 750; https://doi.org/10.3390/antiox13060750 - 20 Jun 2024

Viewed by 1129

Abstract

Studies on adolescent rats, when body composition is changing deeply, reveal that the administration of sodium selenite and selenium nanoparticles (SeNPs), at the same dose, have opposite effects on adipogenesis in white adipose tissue (WAT). To investigate the mechanisms involved in these contrasting [...] Read more.

Studies on adolescent rats, when body composition is changing deeply, reveal that the administration of sodium selenite and selenium nanoparticles (SeNPs), at the same dose, have opposite effects on adipogenesis in white adipose tissue (WAT). To investigate the mechanisms involved in these contrasting effects by means of transcriptomic analysis, three groups of male adolescent rats (n = 18) were used: control (C), selenite supplemented (S), and SeNPs supplemented (NS). Both treated groups received a twofold increase in Se dose compared to the control group through water intake for three weeks. Following treatment, WAT was removed and frozen at −80 °C until subsequent use for RNA extraction, endogenous antioxidant enzymatic activities determination, and quantification of H₂O₂ and malondialdehyde. NS rats displayed a larger number of differentially expressed genes and cellular processes impacted than S rats. Remarkably, these changes involved upregulation of gene expression associated with the immune system, catabolism, mitochondrial function, and oxidative balance. NS rats presented an increase in antioxidant enzymes activity, alongside an accumulation of H₂O₂ and malondialdehyde levels. The expression level of 81 genes related to oxidative stress was significantly affected in NS rats. Analyzing the KEGG pathway enrichment revealed that NS rats exhibited increased activity in key catabolic pathways and decreased activity in crucial growth signaling processes. These changes contribute to the mass decrease in WAT found in NS rats. These results suggest a possible application of SeNPs in WAT reduction and induction of the immune response during adolescence. Full article

(This article belongs to the Special Issue Oxidative Stress in Adipose Tissue)

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17 pages, 3659 KiB

Open AccessArticle

Feature-Based Molecular Network-Assisted Cannabinoid and Flavonoid Profiling of Cannabis sativa Leaves and Their Antioxidant Properties

by Ling Chen, Hong-Ling Li, Hong-Juan Zhou, Guan-Zhong Zhang, Ying Zhang, You-Mei Wang, Meng-Yuan Wang, Hua Yang and Wen Gao

Antioxidants 2024, 13(6), 749; https://doi.org/10.3390/antiox13060749 - 20 Jun 2024

Cited by 1 | Viewed by 1512

Abstract

Cannabis sativa (C. sativa) leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between [...] Read more.

Cannabis sativa (C. sativa) leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of C. sativa leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of C. sativa leaves from various regions. Subsequently, antioxidant activity analysis was conducted on 73 batches of C. sativa leaves, and a partial least squares regression (PLS) model was employed to assess the correlation between the content of cannabinoids and flavonoids in the leaves and their antioxidant activity. A total of 16 cannabinoids and 57 flavonoids were annotated from C. sativa, showing a significant regular geographical distribution. The content of flavonoid-C glycosides in Sichuan leaves is relatively high, and their antioxidant activity is also correspondingly high. However, the leaves in Shaanxi and Xinjiang were primarily composed of flavonoid-O glycosides, and exhibited slightly lower antioxidant activity. A significant positive correlation (p < 0.001) was found between the total flavonoids and cannabinoids and the antioxidant activity of the leaves, and two flavonoids and one cannabinoid were identified as significant contributors. Full article

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13 pages, 1942 KiB

Open AccessArticle

The Antioxidant PAPLAL Protects against Allergic Contact Dermatitis in Experimental Models

by Shuichi Shibuya, Kenji Watanabe and Takahiko Shimizu

Antioxidants 2024, 13(6), 748; https://doi.org/10.3390/antiox13060748 - 20 Jun 2024

Cited by 1 | Viewed by 1722

Abstract

PAPLAL, a mixture of platinum (nPt) and palladium (nPd) nanoparticles, is widely used as a topical agent because of its strong antioxidant activity. Allergic contact dermatitis (ACD) is one of the most common occupational skin diseases worldwide. However, the role of oxidative stress [...] Read more.

PAPLAL, a mixture of platinum (nPt) and palladium (nPd) nanoparticles, is widely used as a topical agent because of its strong antioxidant activity. Allergic contact dermatitis (ACD) is one of the most common occupational skin diseases worldwide. However, the role of oxidative stress in ACD remains unclear. In the present study, we investigated the protective effects of topical PAPLAL treatment on 2,4-dinitrofluorobenzene (DNFB)-induced ACD. DNFB treatment increased 8-isoprostane content; upregulated Xdh, Nox2, and Nox4, pro-oxidant genes; and downregulated Sod1, an antioxidant gene, indicating oxidative damage in the ear skin. PAPLAL therapy significantly reduced ear thickness associated with the downregulation of inflammatory cytokine-related genes. PAPLAL also significantly increased the expression of the stress-response-related genes Ahr and Nrf2, as well as their target genes, but failed to alter the expression of redox-related genes. Furthermore, Sod1 loss worsened ACD pathologies in the ear. These results strongly suggest that PAPLAL protects against ACD through its antioxidant activity and activation of the AHR and NRF2 axes. The antioxidant PAPLAL can be used as a novel topical therapy for ACD that targets oxidative stress. Full article

(This article belongs to the Special Issue Free Radicals, Antioxidants and Oxidative Stress in Aging and Age-Related Diseases)

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21 pages, 1593 KiB

Open AccessReview

Melatonin and Vascular Function

by Leandro Mendes, Marcelo Queiroz and Cristina M. Sena

Antioxidants 2024, 13(6), 747; https://doi.org/10.3390/antiox13060747 - 20 Jun 2024

Cited by 3 | Viewed by 2722

Abstract

The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin secretion, and photoperiod regulates melatonin levels by promoting its production and secretion at night in response to darkness. This hormone is becoming more and [...] Read more.

The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin secretion, and photoperiod regulates melatonin levels by promoting its production and secretion at night in response to darkness. This hormone is becoming more and more understood for its functions as an immune-modulatory, anti-inflammatory, and antioxidant hormone. Melatonin may have a major effect on several diabetes-related disturbances, such as hormonal imbalances, oxidative stress, sleep disturbances, and mood disorders, according to recent research. This has raised interest in investigating the possible therapeutic advantages of melatonin in the treatment of diabetic complications. In addition, several studies have described that melatonin has been linked to the development of diabetes, cancer, Alzheimer’s disease, immune system disorders, and heart diseases. In this review, we will highlight some of the functions of melatonin regarding vascular biology. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Vascular Disease Associated with Diabetes)

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16 pages, 3135 KiB

Open AccessArticle

A Novel Antioxidant, Hydrogen-Rich Coral Calcium Alters Gut Microbiome and Bile Acid Synthesis to Improve Methionine-and-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease

by Hung-Tsung Wu, Chin-Shiang Tsai, Ting-Hsing Chao, Horng-Yih Ou and Liang-Miin Tsai

Antioxidants 2024, 13(6), 746; https://doi.org/10.3390/antiox13060746 - 20 Jun 2024

Cited by 1 | Viewed by 1823

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) has dramatically increased in recent years, and it is highly associated with metabolic diseases, as well as the development of hepatocellular carcinoma. However, effective therapeutic strategies for the treatment of NAFLD are still scarce. Although [...] Read more.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has dramatically increased in recent years, and it is highly associated with metabolic diseases, as well as the development of hepatocellular carcinoma. However, effective therapeutic strategies for the treatment of NAFLD are still scarce. Although hydrogen-rich water shows beneficial effects for hepatic steatosis, the inconvenience limits the application of this antioxidant. In light of this, hydrogen-rich coral calcium (HRCC) was developed due to its convenience and quantifiable characteristics. However, the effects of HRCC on NAFLD are still unknown. In the present study, we found that HRCC treatment improved methionine-and-choline-deficient diet (MCD)-induced hepatic steatosis, increased aspartate aminotransferase and alanine aminotransferase levels, and elevated hepatic inflammatory factor expressions in mice. In addition to the increased expressions of antioxidative enzymes, we found that HRCC increased the expressions of bile acid biosynthesis-related genes, including Cyp8b1 and Cyp27a1. Increased hepatic bile acid contents, such as muricholic acids, 23 nor-deoxycholic acid, glycoursodeoxycholic acid, and cholic acids, were also confirmed in MCD mice treated with HRCC. Since the biogenesis of bile acids is associated with the constitution of gut microbiome, the alterations in gut microbiome by HRCC were evaluated. We found that HRCC significantly changed the constitution of gut microbiome in MCD mice and increased the contents of Anaerobacterium, Acutalibacter, Anaerosacchariphilus, and Corynebacterium. Taken together, HRCC improved MCD-induced NAFLD through anti-inflammatory mechanisms and by increasing antioxidative activities. Additionally, HRCC might alter gut microbiome to change hepatic bile acid contents, exerting beneficial effects for the treatment of NAFLD. Full article

(This article belongs to the Special Issue Antioxidant Compounds from Marine Organisms)

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17 pages, 1188 KiB

Open AccessReview

GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells

by Juan De los Santos-Jiménez, José A. Campos-Sandoval, Francisco J. Alonso, Javier Márquez and José M. Matés

Antioxidants 2024, 13(6), 745; https://doi.org/10.3390/antiox13060745 - 20 Jun 2024

Viewed by 1927

Abstract

A pathway frequently altered in cancer is glutaminolysis, whereby glutaminase (GA) catalyzes the main step as follows: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression [...] Read more.

A pathway frequently altered in cancer is glutaminolysis, whereby glutaminase (GA) catalyzes the main step as follows: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 can function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We reviewed the literature to highlight the critical roles of GLS and GLS2 in restraining ROS and regulating both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes, as well as by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy in the dual activation of ferroptosis and inhibition of cancer cell growth in a ROS-mediated mechanism. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)

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16 pages, 3358 KiB

Open AccessArticle

Innovative Cosmeceutical Ingredients: Harnessing Selenosugar-Linked Hydroxycinnamic Acids for Antioxidant and Wound-Healing Properties

by Giovanna Cimmino, Mauro De Nisco, Simona Piccolella, Claudia Gravina, Silvana Pedatella and Severina Pacifico

Antioxidants 2024, 13(6), 744; https://doi.org/10.3390/antiox13060744 - 20 Jun 2024

Cited by 2 | Viewed by 1338

Abstract

Selenosugars are gaining growing interest due to their antioxidant efficacy, and their ability to inhibit glycosidases, repair skin tissue or reduce endothelial dysfunction. Among selenosugars, those in which selenium replaces heterocyclic oxygen in a 5-membered sugar were our focus, and their coupling with [...] Read more.

Selenosugars are gaining growing interest due to their antioxidant efficacy, and their ability to inhibit glycosidases, repair skin tissue or reduce endothelial dysfunction. Among selenosugars, those in which selenium replaces heterocyclic oxygen in a 5-membered sugar were our focus, and their coupling with phenolic compounds appears to be a strategy aimed at producing new compounds with enhanced antioxidant efficacy. In this context, the Mitsunobu reaction has been advantageously explored to obtain trans-p-coumaroyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, trans-caffeoyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose, and trans-feruloyl-1,4-deoxy-2,3-O-isopropylidene-4-seleno-d-ribose. These compounds underwent removal of the iso-propylidene group, to provide the corresponding hydroxycinnamoyl-1,4-deoxy-4-seleno-d-ribose. All compounds were characterized by Nuclear Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). This latter technique was pivotal for ensuing cellular metabolomics analyses. In fact, after evaluating the anti-radical efficacy through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, which underline the massive role of the phenolic moiety in establishing efficacy, the compounds, whose cytotoxicity was first screened in two highly oxidative-stress-sensitive cells, were tested for their wound healing properties towards human HaCaT keratinocytes cells. Caffeoyl- and feruloyl selenosugars exerted a dose-dependent repair activity, while, as highlighted by the metabolomic approach, they were poorly taken up within the cells. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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20 pages, 7797 KiB

Open AccessArticle

Administration of Bicarbonate Protects Mitochondria, Rescues Retinal Ganglion Cells, and Ameliorates Visual Dysfunction Caused by Oxidative Stress

by Tonking Bastola, Guy A. Perkins, Viet Anh Nguyen Huu, Saeyeon Ju, Keun-Young Kim, Ziyao Shen, Dorota Skowronska-Krawczyk, Robert N. Weinreb and Won-Kyu Ju

Antioxidants 2024, 13(6), 743; https://doi.org/10.3390/antiox13060743 - 19 Jun 2024

Cited by 1 | Viewed by 1826

Abstract

Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway is involved in mitochondrial protection, promoting RGC survival. Soluble adenylyl cyclase (sAC) is a key [...] Read more.

Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway is involved in mitochondrial protection, promoting RGC survival. Soluble adenylyl cyclase (sAC) is a key regulator of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, which is known to protect mitochondria and promote RGC survival. However, the precise molecular mechanisms connecting the sAC-mediated signaling pathway with mitochondrial protection in RGCs against oxidative stress are not well characterized. Here, we demonstrate that sAC plays a critical role in protecting RGC mitochondria from oxidative stress. Using mouse models of oxidative stress induced by ischemic injury and paraquat administration, we found that administration of bicarbonate, as an activator of sAC, protected RGCs, blocked AMP-activated protein kinase activation, inhibited glial activation, and improved visual function. Moreover, we found that this is the result of preserving mitochondrial dynamics (fusion and fission), promoting mitochondrial bioenergetics and biogenesis, and preventing metabolic stress and apoptotic cell death. Notably, the administration of bicarbonate ameliorated mitochondrial dysfunction in RGCs by enhancing mitochondrial biogenesis, preserving mitochondrial structure, and increasing ATP production in oxidatively stressed RGCs. These findings suggest that activating sAC enhances the mitochondrial structure and function in RGCs to counter oxidative stress, consequently promoting RGC protection. We propose that modulation of the sAC-mediated signaling pathway has therapeutic potential acting on RGC mitochondria for treating glaucoma and other retinal diseases. Full article

(This article belongs to the Special Issue Oxidative Stress and the Central Nervous System)

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20 pages, 2619 KiB

Open AccessReview

“Edible Beauty”: The Evolution of Environmentally Friendly Cosmetics and Packaging

by Irene Dini

Antioxidants 2024, 13(6), 742; https://doi.org/10.3390/antiox13060742 - 19 Jun 2024

Viewed by 2513

Abstract

The cosmetics industry plays a significant role in the global economy and consumer lifestyles. Its dynamic and adaptable characteristics make it a key player worldwide. The cosmetics industry generates enormous profits globally, injecting billions of dollars into the world’s economy each year. The [...] Read more.

The cosmetics industry plays a significant role in the global economy and consumer lifestyles. Its dynamic and adaptable characteristics make it a key player worldwide. The cosmetics industry generates enormous profits globally, injecting billions of dollars into the world’s economy each year. The industry’s marketing efforts, product launches, and trends influence consumer behavior and perceptions of beauty, contributing to cultural dialogues and societal norms. This study, conducted with a rigorous bibliometric and systematic literature review, offers a comprehensive overview of recent progress in edible cosmetics. The “skincare you can eat” is an innovative branch of cosmetics that employs food co-products and by-products to create edible skincare and hair products and edible packaging materials to advance human well-being and sustainability while honoring the ecological boundaries of our planet. Nutrients and antioxidants derived from organic waste are used in cosmetics and packaging. Some doubts remain about the capacity of edible packaging to be attractive to consumers and offer a reasonable shelf life for cosmetics, and also about safety. It is desirable for the authorities to guarantee consumer health through carefully regulating labeling requirements and good manufacturing practices for cosmetics and edible packaging. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Cosmetics—2nd Edition)

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17 pages, 1629 KiB

Open AccessReview

Induction of Nitric Oxide and Its Role in Facial Nerve Regeneration According to the Method of Facial Nerve Injury

by Yeon Ju Oh, Dong Keon Yon, Yong Sung Choi, Jinseok Lee, Joon Hyung Yeo, Sung Soo Kim, Jae Min Lee and Seung Geun Yeo

Antioxidants 2024, 13(6), 741; https://doi.org/10.3390/antiox13060741 - 19 Jun 2024

Viewed by 1213

Abstract

Nitric oxide (NO) is an important molecule in cell communication that also plays an important role in many biological processes. Given the dual role of NO in nerve degeneration and regeneration after facial nerve injury, we sought to delve deeper into its role [...] Read more.

Nitric oxide (NO) is an important molecule in cell communication that also plays an important role in many biological processes. Given the dual role of NO in nerve degeneration and regeneration after facial nerve injury, we sought to delve deeper into its role through a systematic literature review. A comprehensive review of the literature employing SCOPUS, PubMed, Cochrane Library, EMBASE, and Google Scholar databases was conducted to evaluate the induction and role of NO in neurodegeneration and regeneration after facial nerve injury. From the 20 papers ultimately reviewed, the central findings were that neuronal nitric oxide synthase(nNOS), endothelial nitric oxide synthase (eNOS), and induced nitric oxide synthase (iNOS) increased or decreased depending on the method of facial nerve damage, damaged area, harvested area, and animal age, and were correlated with degeneration and regeneration of the facial nerve. Research conducted on rats and mice demonstrated that NO, nNOS, eNOS, and iNOS play significant roles in nerve regeneration and degeneration. However, the relationship between nerve damage and NO could not be defined by a simple causal relationship. Instead, the involvement of NOS depends on the type of nerve cell, source of NO, timing, and location of expression, age of the target animal, and proximity of the damage location to the brainstem. Consequently, nNOS, eNOS, and iNOS expression levels and functions may vary significantly. Full article

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20 pages, 2332 KiB

Open AccessArticle

Black Goji Berry (Lycium ruthenicum) Juice Fermented with Lactobacillus rhamnosus GG Enhances Inhibitory Activity against Dipeptidyl Peptidase-IV and Key Steps of Lipid Digestion and Absorption

by Kritmongkhon Kamonsuwan, Vernabelle Balmori, Marisa Marnpae, Charoonsri Chusak, Thavaree Thilavech, Suvimol Charoensiddhi, Scott Smid and Sirichai Adisakwattana

Antioxidants 2024, 13(6), 740; https://doi.org/10.3390/antiox13060740 - 19 Jun 2024

Cited by 1 | Viewed by 1587

Abstract

With the global increase in hyperglycemia and hyperlipidemia, there is an urgent need to explore dietary interventions targeting the inhibition of dipeptidyl peptidase-IV (DPP-IV) and lipid digestion and absorption. This study investigated how Lactobacillus rhamnosus GG (LGG) affects various aspects of black goji [...] Read more.

With the global increase in hyperglycemia and hyperlipidemia, there is an urgent need to explore dietary interventions targeting the inhibition of dipeptidyl peptidase-IV (DPP-IV) and lipid digestion and absorption. This study investigated how Lactobacillus rhamnosus GG (LGG) affects various aspects of black goji berry (BGB) (Lycium ruthenicum Murr.) juice, including changes in physicochemical and functional properties, as well as microbiological and sensory attributes. Throughout the fermentation process with 2.5–10% (w/v) BGB, significantly improved probiotic viability, lactic acid production, and decreased sugar content. While total flavonoids increase, anthocyanins decrease, with no discernible change in antioxidant activities. Metabolite profiling reveals elevated phenolic compounds post-fermentation. Regarding the inhibition of lipid digestion and absorption, fermented BGB exhibits improved bile acid binding, and disrupted cholesterol micellization by approximately threefold compared to non-fermented BGB, while also increasing pancreatic lipase inhibitory activity. Furthermore, a decrease in cholesterol uptake was observed in Caco-2 cells treated with fermented BGB (0.5 mg/mL), with a maximum reduction of 16.94%. Fermented BGB also shows more potent DPP-IV inhibition. Sensory attributes are significantly improved in fermented BGB samples. These findings highlight the potential of BGB as a bioactive resource and a promising non-dairy carrier for LGG, enhancing its anti-hyperglycemic and anti-hyperlipidemic properties. Full article

(This article belongs to the Special Issue Antioxidant Activity of Fermented Foods and Food Microorganisms)

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18 pages, 7137 KiB

Open AccessArticle

Exogenous Oxidative Stress in Human Spermatozoa Induces Opening of the Mitochondrial Permeability Transition Pore: Effect on Mitochondrial Function, Sperm Motility and Induction of Cell Death

by Anita Bravo, Raúl Sánchez, Fabiola Zambrano and Pamela Uribe

Antioxidants 2024, 13(6), 739; https://doi.org/10.3390/antiox13060739 - 18 Jun 2024

Cited by 1 | Viewed by 1456

Abstract

Oxidative stress (OS) and disrupted antioxidant defense mechanisms play a pivotal role in the etiology of male infertility. The alterations in reactive oxygen species (ROS) production and calcium (Ca²⁺) homeostasis are the main activators for the mitochondrial permeability transition pore (mPTP) [...] Read more.

Oxidative stress (OS) and disrupted antioxidant defense mechanisms play a pivotal role in the etiology of male infertility. The alterations in reactive oxygen species (ROS) production and calcium (Ca²⁺) homeostasis are the main activators for the mitochondrial permeability transition pore (mPTP) opening. The mPTP opening is one of the main mechanisms involved in mitochondrial dysfunction in spermatozoa. This alteration in mitochondrial function adversely affects energy supply, sperm motility, and fertilizing capacity and contributes to the development of male infertility. In human spermatozoa, the mPTP opening has been associated with ionomycin-induced endogenous oxidative stress and peroxynitrite-induced nitrosative stress; however, the effect of exogenous oxidative stress on mPTP opening in sperm has not been evaluated. The aim of this study was to determine the effect of exogenous oxidative stress induced by hydrogen peroxide (H₂O₂) on mPTP opening, mitochondrial function, motility, and cell death markers in human spermatozoa. Human spermatozoa were incubated with 3 mmol/L of H₂O₂ for 60 min, and intracellular Ca²⁺ concentration, mPTP opening, mitochondrial membrane potential (ΔΨm), ATP levels, mitochondrial reactive oxygen species (mROS) production, phosphatidylserine (PS) externalization, DNA fragmentation, viability, and sperm motility were evaluated. H₂O₂-induced exogenous oxidative stress caused increased intracellular Ca²⁺, leading to subsequent mPTP opening and alteration of mitochondrial function, characterized by ΔΨm dissipation, decreased ATP levels, increased mROS production, and the subsequent alteration of sperm motility. Furthermore, H₂O₂-induced opening of mPTP was associated with the expression of apoptotic cell death markers including PS externalization and DNA fragmentation. These results highlight the role of exogenous oxidative stress in causing mitochondrial dysfunction, deterioration of sperm motility, and an increase in apoptotic cell death markers, including PS externalization and DNA fragmentation, through the mPTP opening. This study yielded new knowledge regarding the effects of this type of stress on mitochondrial function and specifically on mPTP opening, factors that can contribute to the development of male infertility, considering that the role of mPTP in mitochondrial dysfunction in human sperm is not completely elucidated. Therefore, these findings are relevant to understanding male infertility and may provide an in vitro model for further research aimed at improving human sperm quality. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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15 pages, 2000 KiB

Open AccessArticle

Identification of Phenolic Compounds Present in Three Speedwell (Veronica L.) Species and Their Antioxidant Potential

by Ivana Vrca, Stjepan Orhanović, Ivana Pezelj, Karolina Sušić, Valerija Dunkić, Dario Kremer and Marija Nazlić

Antioxidants 2024, 13(6), 738; https://doi.org/10.3390/antiox13060738 - 17 Jun 2024

Cited by 1 | Viewed by 1335

Abstract

Extracts from Veronica species (speedwells) are known for the various biological activities they show, such as cytotoxic, antimicrobial, anti-inflammatory, and antioxidant activities. Also, the plants from this genus are known as medicinal plants used in traditional medicine worldwide. Phenolic compounds are specialized metabolites [...] Read more.

Extracts from Veronica species (speedwells) are known for the various biological activities they show, such as cytotoxic, antimicrobial, anti-inflammatory, and antioxidant activities. Also, the plants from this genus are known as medicinal plants used in traditional medicine worldwide. Phenolic compounds are specialized metabolites that contribute to biological activity the most. Therefore, the aim of this research is identification and quantification of phenolic compounds present in three Veronica species (Veronica anagallis-aquatica L., Veronica persica Poir., and Veronica polita Fr.) using the liquid chromatography-mass spectrometry (LC-MS/MS) technique. All extracts were tested for antioxidant activity with two methods: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). Also, standards for compounds that were detected in the highest amount in all species were also tested for antioxidant activity. Three different solvents (pure methanol, 80% ethanol, and water) were used for the extraction of phenolic components and their comparison in order to test their antioxidant activity as a final goal. The main compounds present in the tested Veronica extracts were: p-hydroxybenzoic acid, vanillic acid, caffeic acid, gentisic acid, and apigenin. V. anagallis-aquatica contained the highest amount of phenolic components in comparison with the two other tested species, V. persica and V. polita. Caffeic acid showed the highest antioxidant activity in both studied methods with an IC₅₀ value for DPPH activity of 1.99 µg/mL. For the plant extracts, in general, methanolic/ethanolic extracts showed higher activity than water extracts in both methods which was expected, as organic solutions extract more phenolic compounds. This research points to the potential application of extracts of different Veronica species for antioxidant activity. Full article

(This article belongs to the Special Issue Phytochemical Analysis and Evaluation of Antioxidant Properties in Medicinal Plants)

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16 pages, 1722 KiB

Open AccessArticle

The Interactive Effects of the Anti-Sea Lice Pesticide Azamethiphos and Temperature on Oxidative Damage and Antioxidant Responses in the Oyster Ostrea chilensis

by Jaime A. Montory, Victor M. Cubillos, Oscar R. Chaparro, Paulina Gebauer, Matthew R. Lee, Eduardo Ramírez-Kuschel, Francisco Paredes-Molina, Valentina Lara-Sandoval, Juan P. Cumillaf, Luis P. Salas-Yanquin and Joseline A. Büchner-Miranda

Antioxidants 2024, 13(6), 737; https://doi.org/10.3390/antiox13060737 - 17 Jun 2024

Viewed by 1394

Abstract

Azamethiphos is used in the salmon industry to treat sea lice and is subsequently discharged into the sea, which may affect non-target species (NTS). A rise in seawater temperature could enhance the sensitivity of NTS. Thus, in the present investigation, the combined effects [...] Read more.

Azamethiphos is used in the salmon industry to treat sea lice and is subsequently discharged into the sea, which may affect non-target species (NTS). A rise in seawater temperature could enhance the sensitivity of NTS. Thus, in the present investigation, the combined effects of azamethiphos (0 µg L⁻¹, 15 µg L⁻¹ and 100 µg L⁻¹) and temperature (12 °C and 15 °C) was assessed over time (7 days) in the gonads and gills of the oyster Ostrea chilensis, assessing its oxidative damage (lipid peroxidation and protein carbonyls) and total antioxidant capacity. Our results indicated that in gonads and gills, lipid peroxidation levels increased over time during exposure to both pesticide concentrations. Protein carbonyl levels in gills increased significantly in all experimental treatments; however, in gonads, only pesticide concentration and exposure time effected a significant increase in protein damage. In both, gill and gonad temperature did not influence oxidative damage levels. Total antioxidant capacity in gonads was influenced only by temperature treatment, whereas in the gills, neither temperature nor azamethiphos concentration influenced defensive responses. In conclusion, our results indicated the time of pesticide exposure (both concentrations) had a greater influence than temperature on the cellular damage in this oyster. Full article

(This article belongs to the Special Issue Redox Metabolism in Ecophysiology and Evolution, 2nd Edition)

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15 pages, 1135 KiB

Open AccessArticle

Responses of Digestive, Antioxidant, Immunological and Metabolic Enzymes in the Intestines and Liver of Largemouth Bass (Micropterus salmoides) under the Biofloc Model

by Yuqin Jin, Shunlong Meng, Huimin Xu, Chao Song, Limin Fan, Liping Qiu and Dandan Li

Antioxidants 2024, 13(6), 736; https://doi.org/10.3390/antiox13060736 - 17 Jun 2024

Viewed by 1532

Abstract

To investigate the activities of intestinal digestive enzymes, liver antioxidant enzymes, immunological enzymes, and glucometabolic enzymes in largemouth bass (Micropterus salmoides) under the biofloc model, an experiment was conducted in 300-liter glass tanks. The experiment comprised a control group, which was [...] Read more.

To investigate the activities of intestinal digestive enzymes, liver antioxidant enzymes, immunological enzymes, and glucometabolic enzymes in largemouth bass (Micropterus salmoides) under the biofloc model, an experiment was conducted in 300-liter glass tanks. The experiment comprised a control group, which was fed a basal diet, and a biofloc group, where glucose was added to maintain a C/N ratio of 15. Each group had three parallel setups, with a stocking density of 20 fish per tank. The experiment ran for 60 days, employing a zero-water exchange aquaculture model. The results showed that at the end of the culture period, there were no significant differences between the initial weight, final weight, WGR, SGR, and SR of the biofloc group and the control group of largemouth bass (p > 0.05), whereas the lower FCR and the higher PER in the biofloc group were significant (p < 0.05); intestinal α-amylase, trypsin, and lipase activities of largemouth bass in the biofloc group were significantly increased by 37.20%, 64.11%, and 51.69%, respectively, compared with the control group (p < 0.05); liver superoxide dismutase and catalase activities, and total antioxidant capacity of largemouth bass in the biofloc group were significantly increased by 49.26%, 46.87%, and 98.94% (p < 0.05), while the malondialdehyde content was significantly reduced by 19.91% (p < 0.05); liver lysozyme, alkaline phosphatase, and acid phosphatase activities of largemouth bass in the biofloc group were significantly increased by 62.66%, 41.22%, and 29.66%, respectively (p < 0.05); liver glucokinase, pyruvate kinase, glucose-6-phosphate kinase, pyruvate kinase, glucose-6-phosphatase, and glycogen synthase activities were significantly increased by 46.29%, 99.33%, 32.54%, and 26.89%, respectively (p < 0.05). The study showed that the biofloc model of culturing largemouth bass can not only enhance digestive enzyme activities, antioxidant capacity, and immune response but can also promote the process of glucose metabolism and reduce feeding costs. This study provides data support for healthy culturing of largemouth bass in future production, provides a theoretical reference for optimizing the biofloc technology culture model, and is crucial for promoting the healthy and green development of aquaculture. Full article

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17 pages, 4542 KiB

Open AccessArticle

Active DNA Demethylase, TET1, Increases Oxidative Phosphorylation and Sensitizes Ovarian Cancer Stem Cells to Mitochondrial Complex I Inhibitor

by Lin-Yu Chen, Yao-An Shen, Ling-Hui Chu, Po-Hsuan Su, Hui-Chen Wang, Yu-Chun Weng, Shiou-Fu Lin, Kuo-Chang Wen, Phui-Ly Liew and Hung-Cheng Lai

Antioxidants 2024, 13(6), 735; https://doi.org/10.3390/antiox13060735 - 17 Jun 2024

Cited by 1 | Viewed by 1689

Abstract

Ten-eleven translocation 1 (TET1) is a methylcytosine dioxygenase involved in active DNA demethylation. In our previous study, we demonstrated that TET1 reprogrammed the ovarian cancer epigenome, increased stem properties, and activated various regulatory networks, including metabolic networks. However, the role of TET1 in [...] Read more.

Ten-eleven translocation 1 (TET1) is a methylcytosine dioxygenase involved in active DNA demethylation. In our previous study, we demonstrated that TET1 reprogrammed the ovarian cancer epigenome, increased stem properties, and activated various regulatory networks, including metabolic networks. However, the role of TET1 in cancer metabolism remains poorly understood. Herein, we uncovered a demethylated metabolic gene network, especially oxidative phosphorylation (OXPHOS). Contrary to the concept of the Warburg effect in cancer cells, TET1 increased energy production mainly using OXPHOS rather than using glycolysis. Notably, TET1 increased the mitochondrial mass and DNA copy number. TET1 also activated mitochondrial biogenesis genes and adenosine triphosphate production. However, the reactive oxygen species levels were surprisingly decreased. In addition, TET1 increased the basal and maximal respiratory capacities. In an analysis of tricarboxylic acid cycle metabolites, TET1 increased the levels of α-ketoglutarate, which is a coenzyme of TET1 dioxygenase and may provide a positive feedback loop to modify the epigenomic landscape. TET1 also increased the mitochondrial complex I activity. Moreover, the mitochondrial complex I inhibitor, which had synergistic effects with the casein kinase 2 inhibitor, affected ovarian cancer growth. Altogether, TET1-reprogrammed ovarian cancer stem cells shifted the energy source to OXPHOS, which suggested that metabolic intervention might be a novel strategy for ovarian cancer treatment. Full article

(This article belongs to the Special Issue Oxidative Metabolism and Mitochondrial Dysfunction in Metabolic Diseases—2nd Edition)

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12 pages, 852 KiB

Open AccessArticle

From Personal Care to Coastal Concerns: Investigating Polyethylene Glycol Impact on Mussel’s Antioxidant, Physiological, and Cellular Responses

by Cristiana Roberta Multisanti, Giorgia Zicarelli, Alessia Caferro, Mariacristina Filice, Caterina Faggio, Irene Vazzana, Jana Blahova, Pavla Lakdawala, Maria Carmela Cerra, Sandra Imbrogno and Federica Impellitteri

Antioxidants 2024, 13(6), 734; https://doi.org/10.3390/antiox13060734 - 17 Jun 2024

Cited by 8 | Viewed by 1169

Abstract

Pharmaceutical and personal care products (PPCPs) containing persistent and potentially hazardous substances have garnered attention for their ubiquitous presence in natural environments. This study investigated the impact of polyethylene glycol (PEG), a common PPCP component, on Mytilus galloprovincialis. Mussels were subjected to [...] Read more.

Pharmaceutical and personal care products (PPCPs) containing persistent and potentially hazardous substances have garnered attention for their ubiquitous presence in natural environments. This study investigated the impact of polyethylene glycol (PEG), a common PPCP component, on Mytilus galloprovincialis. Mussels were subjected to two PEG concentrations (E1: 0.1 mg/L and E2: 10 mg/L) over 14 days. Oxidative stress markers in both gills and digestive glands were evaluated; cytotoxicity assays were performed on haemolymph and digestive gland cells. Additionally, cell volume regulation (RVD assay) was investigated to assess physiological PEG-induced alterations. In the gills, PEG reduced superoxide dismutase (SOD) activity and increased lipid peroxidation (LPO) at E1. In the digestive gland, only LPO was influenced, while SOD activity and oxidatively modified proteins (OMPs) were unaltered. A significant decrease in cell viability was observed, particularly at E2. Additionally, the RVD assay revealed disruptions in the cells subjected to E2. These findings underscore the effects of PEG exposure on M. galloprovincialis. They are open to further investigations to clarify the environmental implications of PPCPs and the possibility of exploring safer alternatives. Full article

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13 pages, 6280 KiB

Open AccessArticle

Cytotoxic Oxidative Stress Effects of Neutrophil Extracellular Traps’ Components on Cattle Spermatozoa

by Rodrigo Rivera-Concha, Marion León, Aurora Prado-Sanhueza, Raúl Sánchez, Anja Taubert, Carlos Hermosilla, Pamela Uribe and Fabiola Zambrano

Antioxidants 2024, 13(6), 733; https://doi.org/10.3390/antiox13060733 - 17 Jun 2024

Viewed by 1389

Abstract

Bovine spermatozoa are highly susceptible to oxidative stress (OS), and it is known to affect their cellular functions. The main leukocyte producers of reactive oxygen species (ROS) in mammalian semen are polymorphonuclear neutrophils (PMN). PMN activation can result in the formation of neutrophil [...] Read more.

Bovine spermatozoa are highly susceptible to oxidative stress (OS), and it is known to affect their cellular functions. The main leukocyte producers of reactive oxygen species (ROS) in mammalian semen are polymorphonuclear neutrophils (PMN). PMN activation can result in the formation of neutrophil extracellular traps (NETs), which have been shown to affect the motility and function of spermatozoa. However, OS effects on bull spermatozoa derived from individual NETs components have not been investigated. The hypothesis of this study was that specific NETs components might generate OS on bull spermatozoa. Bovine sperm cells were incubated with five NETs-associated molecules, including 30 μg/mL histone 2A (H2A), neutrophil elastase (NE), 1 μg/mL myeloperoxidase (MPO), cathepsin G (Cat-G), and cathelicidin LL37 (LL-37), for a time course ranging from 15 to 240 min. Fluorescence microscopy was used to evaluate the coincubation of bovine PMN and sperm cells. Within 15 min, H2A, NE, and LL-37 caused membrane disruption, while MPO and Cat-G caused OS on bull spermatozoa after 1 h of coincubation. NET formation was observed within 15 min of coincubation in co-cultures of bovine PMN/sperm cells. This study is the first to report on the role of cytotoxic OS effects caused by NETs-derived components in bovine sperm in vitro. Full article

(This article belongs to the Special Issue Effect of Oxidative Stress on Reproduction and Development—2nd Edition)

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15 pages, 1719 KiB

Open AccessArticle

Induction of Semaphorin 3A by Resveratrol and Pinostilbene via Activation of the AHR-NRF2 Axis in Human Keratinocytes

by Gaku Tsuji, Ayako Yumine, Koji Kawamura, Masaki Takemura and Takeshi Nakahara

Antioxidants 2024, 13(6), 732; https://doi.org/10.3390/antiox13060732 - 17 Jun 2024

Viewed by 2069

Abstract

Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is involved in pruritus in inflammatory skin diseases such as atopic dermatitis (AD) and dry skin. We previously reported that tapinarof, a [...] Read more.

Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is involved in pruritus in inflammatory skin diseases such as atopic dermatitis (AD) and dry skin. We previously reported that tapinarof, a stilbene molecule, upregulates SEMA3A in human keratinocytes. We also showed that this mechanism is mediated via the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, and the nuclear factor erythroid 2-related factor 2 (NRF2) axis. Since some stilbenes activate AHR and NRF2, we attempted to identify other stilbenes that upregulate SEMA3A. We analyzed normal human epidermal keratinocytes (NHEKs) treated with 11 types of stilbenes and examined SEMA3A expression. We found that resveratrol and pinostilbene, antioxidant polyphenols, upregulated SEMA3A and increased nuclear AHR and NRF2 expression. In addition, AHR knockdown by small interfering RNA (siRNA) transfection abolished the NRF2 nuclear expression. Furthermore, AHR and NRF2 knockdown by siRNA transfection abrogated resveratrol- and pinostilbene-induced SEMA3A upregulation. Finally, we confirmed that resveratrol and pinostilbene increased SEMA3A promoter activity through NRF2 binding using ChIP-qPCR analysis. These results suggest that resveratrol and pinostilbene upregulate SEMA3A via the AHR–NRF2 axis in human keratinocytes. Full article

(This article belongs to the Special Issue Antioxidants for Skin Health)

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29 pages, 1227 KiB

Open AccessReview

Oxidative Stress as a Target for Non-Pharmacological Intervention in MAFLD: Could There Be a Role for EVOO?

by Aurelio Seidita, Alessandra Cusimano, Alessandra Giuliano, Maria Meli, Antonio Carroccio, Maurizio Soresi and Lydia Giannitrapani

Antioxidants 2024, 13(6), 731; https://doi.org/10.3390/antiox13060731 - 16 Jun 2024

Cited by 2 | Viewed by 2278

Abstract

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in [...] Read more.

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease)

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13 pages, 2171 KiB

Open AccessArticle

Therapeutic Effect of Alpha Lipoic Acid in a Rat Preclinical Model of Preeclampsia: Focus on Maternal Signs, Fetal Growth and Placental Function

by Gabriela Barrientos, Mariano L. Schuman, Maria S. Landa, Elizabeth Robello, Claudio Incardona, Melanie L. Conrad, Monica Galleano and Silvia I. García

Antioxidants 2024, 13(6), 730; https://doi.org/10.3390/antiox13060730 - 16 Jun 2024

Cited by 2 | Viewed by 1750

Abstract

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that [...] Read more.

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19–16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE. Full article

(This article belongs to the Special Issue The Role of Antioxidants in Pregnant Women’s and Children’s Health—2nd Edition)

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25 pages, 3042 KiB

Open AccessReview

Liver Cell Mitophagy in Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis

by Jiaxin Chen, Linge Jian, Yangkun Guo, Chengwei Tang, Zhiyin Huang and Jinhang Gao

Antioxidants 2024, 13(6), 729; https://doi.org/10.3390/antiox13060729 - 15 Jun 2024

Cited by 2 | Viewed by 2633

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. MASLD and its advanced-stage liver fibrosis and cirrhosis are the leading causes of liver failure and liver-related death worldwide. Mitochondria are crucial organelles in liver cells for energy generation and [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. MASLD and its advanced-stage liver fibrosis and cirrhosis are the leading causes of liver failure and liver-related death worldwide. Mitochondria are crucial organelles in liver cells for energy generation and the oxidative metabolism of fatty acids and carbohydrates. Recently, mitochondrial dysfunction in liver cells has been shown to play a vital role in the pathogenesis of MASLD and liver fibrosis. Mitophagy, a selective form of autophagy, removes and recycles impaired mitochondria. Although significant advances have been made in understanding mitophagy in liver diseases, adequate summaries concerning the contribution of liver cell mitophagy to MASLD and liver fibrosis are lacking. This review will clarify the mechanism of liver cell mitophagy in the development of MASLD and liver fibrosis, including in hepatocytes, macrophages, hepatic stellate cells, and liver sinusoidal endothelial cells. In addition, therapeutic strategies or compounds related to hepatic mitophagy are also summarized. In conclusion, mitophagy-related therapeutic strategies or compounds might be translational for the clinical treatment of MASLD and liver fibrosis. Full article

(This article belongs to the Special Issue Role of Oxidative Stress in Mitochondrial Function: Relevance for Liver Function)

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14 pages, 1491 KiB

Open AccessArticle

Chemical Compositions and In Vitro Antioxidant Activities of the Essential Oils of Sawdust and Resin-Rich Bark from Azorean Cryptomeria japonica (Cupressaceae)

by Ana Lima, Filipe Arruda, Tanner Wortham, Alexandre Janeiro, Tânia Rodrigues, José Baptista and Elisabete Lima

Antioxidants 2024, 13(6), 728; https://doi.org/10.3390/antiox13060728 - 15 Jun 2024

Cited by 2 | Viewed by 1242

Abstract

In the Azores archipelago (Portugal), forest operations and wood industry generate large amounts of Cryptomeria japonica biomass residues (CJBR), which can be used to produce valuable essential oils (EOs). In this study, we evaluated the chemical composition and antioxidant activities of EOs from [...] Read more.

In the Azores archipelago (Portugal), forest operations and wood industry generate large amounts of Cryptomeria japonica biomass residues (CJBR), which can be used to produce valuable essential oils (EOs). In this study, we evaluated the chemical composition and antioxidant activities of EOs from Azorean C. japonica sawdust (CJS) and resin-rich bark (CJRRB). The CJS and CJRRB EOs, obtained via hydrodistillation, showed different yield values (0.27% vs. 0.80% v/w, dry weight) and also different chemical profiles, as assessed using GC/MS. A total of 64 and 85 components were identified in CJS and CJRRB EOs, representing 95.7% and 96.9% of the total composition, respectively. The major components in CJS EO were oxygenated sesquiterpenes (mainly α+β-eudesmol, 1-epicubenol, and cubebol), while in CJRRB EO, the major components were monoterpene hydrocarbons, including α-pinene, δ-3-carene, and limonene (66.6% vs. 6.4% for oxygenated sesquiterpenes and 0% vs. 64% for monoterpene hydrocarbons, respectively). Antioxidant activity was estimated using (i) two radical-based assays, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity, and (ii) a lipid model assay, β-carotene-linoleic acid bleaching activity (BCBA). Both CJS and CJRRB EOs exhibited concentration-dependent antioxidant activities, and their DPPH, ABTS, and BCBA EC₅₀ values were 1107 vs. 1275 µg/mL, 260 vs. 498 µg/mL, and 1764 vs. 662 µg/mL, respectively. The results indicate that both EOs were able to exert antioxidant activity via different mechanisms of action. Therefore, Azorean CJS and CJRRB may be sustainable sources for antioxidant compounds. This study expands the chemical and biological knowledge of CJBR EOs and, consequently, adds more value to the C. japonica EO industry. Full article

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14 pages, 2970 KiB

Open AccessArticle

In Vitro Biological Activities of Hesperidin-Related Compounds with Different Solubility

by Hyo-Jun Lee, Sun-Hyung Lee, Sun-Ki Hong, Bog-Im Gil and Kyung-Ae Lee

Antioxidants 2024, 13(6), 727; https://doi.org/10.3390/antiox13060727 - 14 Jun 2024

Viewed by 1210

Abstract

The biological activities of hesperidin-related compounds, such as hesperetin laurate (HTL), hesperetin (HT), hesperidin (HD), and hesperidin glucoside (HDG), were investigated in vitro. The compounds showed different hydrophobicities, and the octanol–water partition coefficient log P were 7.28 ± 0.06 for HTL, 2.59 ± [...] Read more.

The biological activities of hesperidin-related compounds, such as hesperetin laurate (HTL), hesperetin (HT), hesperidin (HD), and hesperidin glucoside (HDG), were investigated in vitro. The compounds showed different hydrophobicities, and the octanol–water partition coefficient log P were 7.28 ± 0.06 for HTL, 2.59 ± 0.04 for HT, 2.13 ± 0.03 for HD, and −3.45 ± 0.06 for HDG, respectively. In the DPPH assay and β-carotene bleaching assay to determine antioxidant capacity, all compounds tested showed antioxidant activity in a concentration-dependent manner, although to varying degrees. HTL and HT showed similarly high activities compared to HD or HDG. HD and HDG did not show a significant difference despite the difference in solubility between the two. Cytotoxicity was high; in the order of hydrophobicity—HTL > HT > HD > HDL in keratinocyte HaCaT cells. All compounds tested showed reducing effects on cellular inflammatory mediators and cytokines induced by UV irradiation. However, HTL and HT effectively reduced nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) levels compared to HD and HDG. The inhibitory effects of hesperidin-related compounds on skin-resident microorganisms were evaluated by measuring minimum inhibitory concentration (MIC). HTL showed the highest inhibitory effects against Staphylococcus aureus, Cutibacterium acnes, Candida albicans, and Malassezia furfur, followed by HT, while HD and HDF showed little effect. In conclusion, the hydrophobicity of hesperidin-related compounds was estimated to be important for biological activity in vitro, as was the presence or absence of the sugar moiety. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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27 pages, 4963 KiB

Open AccessArticle

The Antioxidant Potential and Anticancer Activity of Halodule uninervis Ethanolic Extract against Triple-Negative Breast Cancer Cells

by Nadine Wehbe, Adnan Badran, Serine Baydoun, Ali Al-Sawalmih, Marc Maresca, Elias Baydoun and Joelle Edward Mesmar

Antioxidants 2024, 13(6), 726; https://doi.org/10.3390/antiox13060726 - 14 Jun 2024

Cited by 1 | Viewed by 1616

Abstract

Natural remedies have been indispensable to traditional medicine practices for generations, offering therapeutic solutions for various ailments. In modern times, these natural products continue to play a pivotal role in the discovery of new drugs, especially for cancer treatment. The marine ecosystem offers [...] Read more.

Natural remedies have been indispensable to traditional medicine practices for generations, offering therapeutic solutions for various ailments. In modern times, these natural products continue to play a pivotal role in the discovery of new drugs, especially for cancer treatment. The marine ecosystem offers a wide range of plants with potential anticancer activities due to their distinct biochemical diversity and adaptation to extreme situations. The seagrass Halodule uninervis is rich in diverse bioactive metabolites that bestow the plant with various pharmacological properties. However, its anticancer activity against invasive triple-negative breast cancer (TNBC) is still poorly investigated. In the present study, the phytochemical composition of an ethanolic extract of H. uninervis (HUE) was screened, and its antioxidant potential was evaluated. Moreover, the anticancer potential of HUE against MDA-MB-231 cells was investigated along with the possible underlying mechanisms of action. Our results showed that HUE is rich in diverse phytochemicals that are known for their antioxidant and anticancer effects. In MDA-MB-231 cells, HUE targeted the hallmarks of cancer, including cell proliferation, adhesion, migration, invasion, and angiogenesis. The HUE-mediated anti-proliferative and anti-metastatic effects were associated with the downregulation of the proto-oncogenic STAT3 signaling pathway. Taken together, H. uninervis could serve as a valuable source for developing novel drugs targeting TNBC. Full article

(This article belongs to the Special Issue Antioxidant and Protective Effects of Plant Extracts)

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17 pages, 13287 KiB

Open AccessArticle

Dopamine D2 Receptor Activation Blocks GluA2/ROS Positive Feedback Loop to Alienate Chronic-Migraine-Associated Pain Sensitization

by Wei Zhang, Xiaoyan Zhang, Ming Lei, Dunke Zhang, Guangcheng Qin, Jiying Zhou, Lichun Ji and Lixue Chen

Antioxidants 2024, 13(6), 725; https://doi.org/10.3390/antiox13060725 - 14 Jun 2024

Viewed by 1322

Abstract

Chronic migraine is a disabling disorder without effective therapeutic medicine. AMPA receptors have been proven to be essential to pathological pain and headaches, but the related regulatory mechanisms in chronic migraine have not yet been explored. In this study, we found that the [...] Read more.

Chronic migraine is a disabling disorder without effective therapeutic medicine. AMPA receptors have been proven to be essential to pathological pain and headaches, but the related regulatory mechanisms in chronic migraine have not yet been explored. In this study, we found that the level of surface GluA2 was reduced in chronic migraine rats. Tat-GluR23Y (a GluA2 endocytosis inhibitor) reduced calcium inward flow and weakened synaptic structures, thus alleviating migraine-like pain sensitization. In addition, the inhibition of GluA2 endocytosis reduced the calcium influx and alleviated mitochondrial calcium overload and ROS generation in primary neurons. Furthermore, our results showed that ROS can induce allodynia and GluA2 endocytosis in rats, thus promoting migraine-like pain sensitization. In our previous study, the dopamine D2 receptor was identified as a potential target in the treatment of chronic migraine, and here we found that dopamine D2 receptor activation suppressed chronic-migraine-related pain sensitization through blocking the GluA2/ROS positive feedback loop in vivo and in vitro. Additionally, ligustrazine, a core component of ligusticum chuanxiong, was shown to target the dopamine D2 receptor, thereby alleviating ROS production and abnormal nociception in CM rats. This study provides valuable insight into the treatment of chronic migraine. Full article

(This article belongs to the Special Issue New Treatments with Antioxidants for Chronic Pain and Mood Disorders Associated)

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16 pages, 1459 KiB

Open AccessArticle

Changes in Faecal Microbiota Profile and Plasma Biomarkers following the Administration of an Antioxidant Oleuropein-Rich Leaf Extract in a Rat Model Mimicking Colorectal Cancer

by Sofia Chioccioli, Gabriele Rocchetti, Jessica Ruzzolini, Silvia Urciuoli, Francesco Vitali, Gianluca Bartolucci, Marco Pallecchi, Giovanna Caderni, Carlotta De Filippo, Chiara Nediani and Luigi Lucini

Antioxidants 2024, 13(6), 724; https://doi.org/10.3390/antiox13060724 - 14 Jun 2024

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Abstract

Oleuropein (OLE), a phenolic compound particularly abundant in the olive leaves, has been reported to have beneficial activities against colorectal cancer (CRC). In vitro studies suggested that these latter could be due to a modulation of the intestinal microbiota. Aiming to evaluate if [...] Read more.

Oleuropein (OLE), a phenolic compound particularly abundant in the olive leaves, has been reported to have beneficial activities against colorectal cancer (CRC). In vitro studies suggested that these latter could be due to a modulation of the intestinal microbiota. Aiming to evaluate if OLE could affect the intestinal microbiota and the plasma metabolome, an antioxidant oleuropein-rich leaf extract (ORLE) was administered for one week to PIRC rats (F344/NTac-Apc^am1137), a genetic model mimicking CRC. ORLE treatment significantly modulated the gut microbiota composition. Plasma metabolomic profiles revealed a significant predictive ability for amino acids, medium-chain fatty acids, and aldehydes. Pathway analysis revealed a significant decrease in phosphatidylcholine accumulation (LogFC = −1.67) in PIRC rats. These results suggest a significant effect of ORLE administration on faecal microbiota profiles and plasma metabolomes, thereby offering new omics-based insights into its protective role in CRC progression. Full article

(This article belongs to the Special Issue Antioxidant Status in Tumor Progression)

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12 pages, 4122 KiB

Open AccessArticle

Antioxidant Activity and Oxidative Damage Associated with Seeding Surgery for Pearl Culture in the Winged Pearl Oyster Pteria sterna

by Andrés Granados-Amores, Ángel I. Campa-Córdova, Héctor Acosta-Salmón, Carlos Angulo, Tania Zenteno-Savín, Carmen Rodríguez-Jaramillo and Pedro E. Saucedo

Antioxidants 2024, 13(6), 723; https://doi.org/10.3390/antiox13060723 - 14 Jun 2024

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Abstract

To evaluate the antioxidant activity and oxidative damage by relaxing, wounding, and seeding of a saibo of different origin on Pteria sterna hosts, five oyster treatments were included: (1) relaxed (REL) but neither wounded nor seeded; (2) relaxed and wounded (WOU) but not [...] Read more.

To evaluate the antioxidant activity and oxidative damage by relaxing, wounding, and seeding of a saibo of different origin on Pteria sterna hosts, five oyster treatments were included: (1) relaxed (REL) but neither wounded nor seeded; (2) relaxed and wounded (WOU) but not seeded; (3) relaxed, wounded, and seeded with an allograft (ALL); (4) relaxed, wounded, and seeded with an autograft (AUT); and (5) unrelaxed, unwounded, and unseeded as control (CTR). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid (TBARS) activity were quantified between 3 and 24 h post-seeding. Compared to the CTR oysters, which did not suffer oxidative stress, SOD activity significantly decreased in the gonad and digestive gland in all treatments and decreased in mantle tissue in AUT oysters; this indicates that the entire process of preparing oysters for pearl culture (relaxing, wounding, and seeding) generates oxidative stress in the host. CAT was not a sensitive enzyme for measuring the short-term response of oysters to the wounding–seeding processes but rather a more prolonged or chronic stress. Similar to SOD, the lowest GPx and TBARS activity in seeded oysters evidenced their susceptibility to oxidative stress and damage, particularly in the WOU treatment. Evidence from this study indicates that SOD is a more sensitive enzyme for measuring the short-term response of the host oyster to the wounding and seeding of a saibo. It is also clear that the host undergoes stress at all stages of the pearl culture process, mostly during gonad wounding and regardless of the origin of saibo. Full article

(This article belongs to the Special Issue Antioxidants Benefits in Aquaculture 2.0)

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