International Journal of Molecular Sciences

Editorial

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Open AccessEditorial

Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects

by Antonio Mancini and Andrea Silvestrini

Int. J. Mol. Sci. 2022, 23(8), 4346; https://doi.org/10.3390/ijms23084346 - 14 Apr 2022

Cited by 4 | Viewed by 1532

Abstract

The aim of this Special Issue is to highlight oxidative stress (OS) as a mechanism underlying a major risk factor for several human diseases [...] Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

Research

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19 pages, 2687 KiB

Open AccessArticle

Effect of Melatonin on Redox Enzymes Daily Gene Expression in Perirenal and Subcutaneous Adipose Tissue of a Diet Induced Obesity Model

by Pilar Fernández-Mateos, Pilar Cano-Barquilla, Vanesa Jiménez-Ortega, Leire Virto, Juliana Pérez-Miguelsanz and Ana I. Esquifino

Int. J. Mol. Sci. 2023, 24(2), 960; https://doi.org/10.3390/ijms24020960 - 4 Jan 2023

Viewed by 1604

Abstract

Increased adiposity is related to oxidative stress, inflammation and metabolic disorders. Our group has shown that melatonin totally or partially prevents the alterations that obesity causes in some neuroendocrine and inflammatory parameters indicative of oxidative stress. This study analyzes the effects of HFD [...] Read more.

Increased adiposity is related to oxidative stress, inflammation and metabolic disorders. Our group has shown that melatonin totally or partially prevents the alterations that obesity causes in some neuroendocrine and inflammatory parameters indicative of oxidative stress. This study analyzes the effects of HFD on the relative gene expression of several redox balance enzymes on adult male Wistar rats subcutaneous (SAT) and perirenal adipose tissue (PRAT) and the possible preventive role of melatonin. Three experimental groups were established: control, high fat diet (HFD) and HFD plus 25 μg/mL melatonin in tap water. After 11 weeks, animals were sacrificed at 09:00 a.m. and 01:00 a.m. and PRAT and SAT were collected for selected redox enzymes qRT-PCR. Differential expression of redox enzyme genes, except for SOD^Mn, GPx and catalase, was observed in the control group as a function of fat depot. HFD causes the disappearance of the temporal changes in the expression of the genes studied in the two fat depots analyzed. PRAT seems to be more sensitive than SAT to increased oxidative stress induced by obesity. Melatonin combined with a HFD intake, partially prevents the effects of the HFD on the gene expression of the redox enzymes. According to our results, melatonin selectively prevents changes in the relative gene expression of redox enzymes in PRAT and SAT of animals fed an HFD. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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26 pages, 8502 KiB

Open AccessArticle

Oxidative Stress and Nuclear Reprogramming: A Pilot Study of the Effects of Reactive Oxygen Species on Architectural and Epigenetic Landscapes

by Claudio Casali, Stella Siciliani, Luca Galgano and Marco Biggiogera

Int. J. Mol. Sci. 2023, 24(1), 153; https://doi.org/10.3390/ijms24010153 - 21 Dec 2022

Cited by 4 | Viewed by 1791

Abstract

Cell genome integrity is continuously threatened by various sources, both endogenous and exogenous. Oxidative stress causes a multitude of damages, severely affecting cell viability, fidelity of genetic information inheritance, and determining profound alterations in gene expression. Epigenetics represents a major form of gene [...] Read more.

Cell genome integrity is continuously threatened by various sources, both endogenous and exogenous. Oxidative stress causes a multitude of damages, severely affecting cell viability, fidelity of genetic information inheritance, and determining profound alterations in gene expression. Epigenetics represents a major form of gene expression modulation, influencing DNA accessibility to transcription factors and the overall nuclear architecture. When assessing the stress-induced epigenome reprogramming, widely diffused biochemical and molecular approaches commonly fail to incorporate analyses such as architectural chromatin alterations and target molecules precise spatial localization. Unveiling the significance of the nuclear response to the oxidative stress, as well as the functional effects over the chromatin organization, may reveal targets and strategies for approaches aiming at limiting the impact on cellular stability. For these reasons, we utilized potassium bromate treatment, a stressor able to induce DNA damages without altering the cellular microenvironment, hence purely modeling nuclear oxidative stress. By means of high-resolution techniques, we described profound alterations in DNA and histone epigenetic modifications and in chromatin organization in response to the reactive oxygen species. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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17 pages, 2713 KiB

Open AccessArticle

Aspartame Consumption, Mitochondrial Disorder-Induced Impaired Ovarian Function, and Infertility Risk

by Yang-Ching Chen, Yen-Chia Yeh, Yu-Fang Lin, Heng-Kien Au, Shih-Min Hsia, Yue-Hwa Chen and Rong-Hong Hsieh

Int. J. Mol. Sci. 2022, 23(21), 12740; https://doi.org/10.3390/ijms232112740 - 22 Oct 2022

Cited by 9 | Viewed by 4800

Abstract

Frequent consumption of diet drinks was associated with oocyte dysmorphism, decreased embryo quality, and an adverse effect on pregnancy rate. We investigated the harmful effects of aspartame and potential mechanisms through which it increases infertility risk through clinical observations and in vivo and [...] Read more.

Frequent consumption of diet drinks was associated with oocyte dysmorphism, decreased embryo quality, and an adverse effect on pregnancy rate. We investigated the harmful effects of aspartame and potential mechanisms through which it increases infertility risk through clinical observations and in vivo and in vitro studies. Methods: We established a cohort of 840 pregnant women and retrospectively determined their time to conceive. We assessed the estrus cycle, the anti-Mullerian hormone level, ovarian oxidative stress, and ovarian mitochondrial function in an animal study. We also evaluated mitochondria function, mitochondrial biogenesis, and progesterone release with in vitro studies. Aspartame consumption was associated with increased infertility risk in the younger women (Odds ratio: 1.79, 95% confidence interval: 1.00, 3.22). The results of the in vivo study revealed that aspartame disrupted the estrus cycle and reduced the anti-Mullerian hormone level. Aspartame treatment also suppressed antioxidative activities and resulted in higher oxidative stress in the ovaries and granulosa cells. This phenomenon is caused by an aspartame-induced decline in mitochondrial function (maximal respiration, spare respiratory capacity, and ATP production capacity) and triggered mitochondrial biogenesis (assessed by examining the energy depletion signaling-related factors sirtuin-1, phosphorylated adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator-1α, and nuclear respiratory factor 1 expression levels). Aspartame may alter fertility by reserving fewer follicles in the ovary and disrupting steroidogenesis in granulosa cells. Hence, women preparing for pregnancy are suggested to reduce aspartame consumption and avoid oxidative stressors of the ovaries. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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26 pages, 4456 KiB

Open AccessArticle

Heterozygous Loss of KRIT1 in Mice Affects Metabolic Functions of the Liver, Promoting Hepatic Oxidative and Glycative Stress

by Raffaella Mastrocola, Eleonora Aimaretti, Gustavo Ferreira Alves, Alessia Sofia Cento, Claudia Fornelli, Federica Dal Bello, Chiara Ferraris, Luca Goitre, Andrea Perrelli and Saverio Francesco Retta

Int. J. Mol. Sci. 2022, 23(19), 11151; https://doi.org/10.3390/ijms231911151 - 22 Sep 2022

Cited by 7 | Viewed by 1951

Abstract

KRIT1 loss-of-function mutations underlie the pathogenesis of Cerebral Cavernous Malformation (CCM), a major vascular disease affecting the central nervous system (CNS). However, KRIT1 is also expressed outside the CNS and modulates key regulators of metabolic and oxy-inflammatory pathways, including the master transcription factor [...] Read more.

KRIT1 loss-of-function mutations underlie the pathogenesis of Cerebral Cavernous Malformation (CCM), a major vascular disease affecting the central nervous system (CNS). However, KRIT1 is also expressed outside the CNS and modulates key regulators of metabolic and oxy-inflammatory pathways, including the master transcription factor FoxO1, suggesting a widespread functional significance. Herein, we show that the KRIT1/FoxO1 axis is implicated in liver metabolic functions and antioxidative/antiglycative defenses. Indeed, by performing comparative studies in KRIT1 heterozygous (KRIT1^+/−) and wild-type mice, we found that KRIT1 haploinsufficiency resulted in FoxO1 expression/activity downregulation in the liver, and affected hepatic FoxO1-dependent signaling pathways, which are markers of major metabolic processes, including gluconeogenesis, glycolysis, mitochondrial respiration, and glycogen synthesis. Moreover, it caused sustained activation of the master antioxidant transcription factor Nrf2, hepatic accumulation of advanced glycation end-products (AGEs), and abnormal expression/activity of AGE receptors and detoxifying systems. Furthermore, it was associated with an impairment of food intake, systemic glucose disposal, and plasma levels of insulin. Specific molecular alterations detected in the liver of KRIT1^+/− mice were also confirmed in KRIT1 knockout cells. Overall, our findings demonstrated, for the first time, that KRIT1 haploinsufficiency affects glucose homeostasis and liver metabolic and antioxidative/antiglycative functions, thus inspiring future basic and translational studies. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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15 pages, 1832 KiB

Open AccessArticle

Protein Profiling of a Cellular Model of NAFLD by Advanced Bioanalytical Approaches

by Alessandra Anna Altomare, Gilda Aiello, Jessica Leite Garcia, Giulia Garrone, Beatrice Zoanni, Marina Carini, Giancarlo Aldini and Alfonsina D’Amato

Int. J. Mol. Sci. 2022, 23(16), 9025; https://doi.org/10.3390/ijms23169025 - 12 Aug 2022

Cited by 3 | Viewed by 2802

Abstract

Advanced quantitative bioanalytical approaches in combination with network analyses allow us to answer complex biological questions, such as the description of changes in protein profiles under disease conditions or upon treatment with drugs. In the present work, three quantitative proteomic approaches—either based on [...] Read more.

Advanced quantitative bioanalytical approaches in combination with network analyses allow us to answer complex biological questions, such as the description of changes in protein profiles under disease conditions or upon treatment with drugs. In the present work, three quantitative proteomic approaches—either based on labelling or not—in combination with network analyses were applied to a new in vitro cellular model of nonalcoholic fatty liver disease (NAFLD) for the first time. This disease is characterized by the accumulation of lipids, inflammation, fibrosis, and insulin resistance. Hepatic G2 cells were used as model, and NAFLD was induced by a complex of oleic acid and bovine albumin. The development of the disease was verified by lipid vesicle staining and by the increase in the expression of perilipin-2—a protein constitutively present in the vesicles during NAFLD. The nLC–MS/MS analyses of peptide samples obtained from three different proteomic approaches resulted in accurate and reproducible quantitative data of protein fold-change expressed in NAFLD versus control cells. The differentially regulated proteins were used to evaluate the involved and statistically enriched pathways. Network analyses highlighted several functional and disease modules affected by NAFLD, such as inflammation, oxidative stress defense, cell proliferation, and ferroptosis. Each quantitative approach allowed the identification of similar modulated pathways. The combination of the three approaches improved the power of statistical network analyses by increasing the number of involved proteins and their fold-change. In conclusion, the application of advanced bioanalytical approaches in combination with pathway analyses allows the in-depth and accurate description of the protein profile of an in vitro cellular model of NAFLD by using high-resolution quantitative mass spectrometry data. This model could be extremely useful in the discovery of new drugs to modulate the equilibrium NAFLD health state. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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16 pages, 4684 KiB

Open AccessArticle

Impairment in the Intestinal Morphology and in the Immunopositivity of Toll-like Receptor-4 and Other Proteins in an Autistic Mouse Model

by Caterina Franco, Marzia Gianò, Gaia Favero and Rita Rezzani

Int. J. Mol. Sci. 2022, 23(15), 8731; https://doi.org/10.3390/ijms23158731 - 5 Aug 2022

Cited by 6 | Viewed by 2331

Abstract

Autism spectrum disorder (ASD) identifies a neurodevelopmental disease defined by social impairments and repetitive or stereotyped behaviors. The etiology of ASD remains unclear; it primarily affects the brain, but a link between gastrointestinal (GI) diseases, inflammatory mucosal pathology and this disorder has been [...] Read more.

Autism spectrum disorder (ASD) identifies a neurodevelopmental disease defined by social impairments and repetitive or stereotyped behaviors. The etiology of ASD remains unclear; it primarily affects the brain, but a link between gastrointestinal (GI) diseases, inflammatory mucosal pathology and this disorder has been suggested. In particular, a central role seems to be played by an imbalance in pro-and anti-inflammatory cytokines, oxidative stress, and apoptosis. Toll-like receptor 4 (TLR4) is a protein of innate immunity responsible for the regulation and maintenance of intestinal homeostasis. Through histochemical and immunohistochemical evaluations we analyzed the intestinal morphology and the immunopositivity of TLR4 and of other pro-inflammatory and apoptotic proteins in BTBR T+Itpr3tf/J mice. Morphological data showed that the mucosal tunica presented longer intestinal villi. The length of the villi and the epithelial surface determine the exchanges of the intestinal mucosa with luminal contents, modifying the microbiota composition. The biochemical and immunohistochemical results indicated a close relationship among the increase of TLR4 and the activation of NF-kB subunits (p65 and p50) and pro-inflammatory and apoptotic proteins, such as cyclooxygenase-2, interleukin-1β, inducible nitric oxide synthase, tumor nuclear factor—alpha, caspase-3, caspase-8. These preliminary results require more in-depth study but they suggest the TLR4 signaling pathway as a possible target for therapeutic approaches to reduce GI disorders in ASD. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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14 pages, 7712 KiB

Open AccessArticle

Local Epidermal Endocrine Estrogen Protects Human Melanocytes against Oxidative Stress, a Novel Insight into Vitiligo Pathology

by Asako Yamamoto, Lingli Yang, Yasutaka Kuroda, Jiao Guo, Lanting Teng, Daisuke Tsuruta and Ichiro Katayama

Int. J. Mol. Sci. 2021, 22(1), 269; https://doi.org/10.3390/ijms22010269 - 29 Dec 2020

Cited by 8 | Viewed by 3298

Abstract

As the outermost barrier of the body, skin is a major target of oxidative stress. In the brain, estrogen has been reported synthesized locally and protects neurons from oxidative stress. Here, we explored whether estrogen is also locally synthesized in the skin to [...] Read more.

As the outermost barrier of the body, skin is a major target of oxidative stress. In the brain, estrogen has been reported synthesized locally and protects neurons from oxidative stress. Here, we explored whether estrogen is also locally synthesized in the skin to protect from oxidative stress and whether aberrant local estrogen synthesis is involved in skin disorders. Enzymes and estrogen receptor expression in skin cells were examined first by quantitative real-time PCR and Western blot analyses. Interestingly, the estrogen synthesis enzyme was mainly localized in epidermal keratinocytes and estrogen receptors were mainly expressed in melanocytes among 13 kinds of cultured human skin cells. The most abundant estrogen synthesis enzyme expressed in the epidermis was 17β-hydroxysteroid dehydrogenase 1 (HSD17β1) localized in keratinocytes, and the most dominant estrogen receptor expressed in the epidermis was G protein-coupled estrogen receptor 1 (GPER1) in melanocytes. To investigate whether keratinocyte-derived estradiol could protect melanocytes from oxidative stress, cultured human primary epidermal melanocytes (HEMn-MPs) were treated with H₂O₂ in the presence or absence of 17β estradiol or co-cultured with HSD17β1 siRNA-transfected keratinocytes. Keratinocyte-derived estradiol exhibited protective effects against H₂O₂-induced cell death. Further, reduced expression of HSD17β1 in the epidermis of skin from vitiligo patients was observed compared to the skin from healthy donors or in the normal portions of the skin in vitiligo patients. Our results suggest a possible new target for interventions that may be used in combination with current therapies for patients with vitiligo. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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18 pages, 2435 KiB

Open AccessArticle

Coenzyme Q Depletion Reshapes MCF-7 Cells Metabolism

by Wenping Wang, Irene Liparulo, Nicola Rizzardi, Paola Bolignano, Natalia Calonghi, Christian Bergamini and Romana Fato

Int. J. Mol. Sci. 2021, 22(1), 198; https://doi.org/10.3390/ijms22010198 - 28 Dec 2020

Cited by 11 | Viewed by 3494

Abstract

Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells. Method: The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 [...] Read more.

Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells. Method: The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 enzyme, which catalyzes one of the final reactions in the biosynthetic pathway of CoQ. The bioenergetic and metabolic characteristics of control and coenzyme Q depleted cells were investigated using polarographic and spectroscopic assays. The effect of CoQ depletion on cell growth was analyzed in different metabolic conditions. Results: we showed that cancer cells could cope from energetic and oxidative stress due to mitochondrial dysfunction by reshaping their metabolism. In CoQ depleted cells, the glycolysis was upregulated together with increased glucose consumption, overexpression of GLUT1 and GLUT3, as well as activation of pyruvate kinase (PK). Moreover, the lactate secretion rate was reduced, suggesting that the pyruvate flux was redirected, toward anabolic pathways. Finally, we found a different expression pattern in enzymes involved in glutamine metabolism, and TCA cycle in CoQ depleted cells in comparison to controls. Conclusion: This work elucidated the metabolic alterations in CoQ-depleted cells and provided an insightful understanding of cancer metabolism targeting. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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16 pages, 4343 KiB

Open AccessArticle

Deletion of Thioredoxin-Interacting Protein (TXNIP) Abrogates High Fat Diet-Induced Retinal Leukostasis, Barrier Dysfunction and Microvascular Degeneration in a Mouse Obesity Model

by Islam N. Mohamed, Nader Sheibani and Azza B. El-Remessy

Int. J. Mol. Sci. 2020, 21(11), 3983; https://doi.org/10.3390/ijms21113983 - 1 Jun 2020

Cited by 10 | Viewed by 3021

Abstract

We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and interaction with thioredoxin-interacting protein (TXNIP). Here, the specific contribution of TXNIP and the impact of HFD on retinal [...] Read more.

We have shown that a high fat diet (HFD) induces the activation of retinal NOD-like receptor protein (NLRP3)-inflammasome that is associated with enhanced expression and interaction with thioredoxin-interacting protein (TXNIP). Here, the specific contribution of TXNIP and the impact of HFD on retinal leukostasis, barrier dysfunction and microvascular degeneration were investigated. Wild-type (WT) and TXNIP knockout (TKO) mice were fed with normal diet or 60% HFD for 8–18 weeks. TXNIP was overexpressed or silenced in human retinal endothelial cells (REC). At 8 weeks, HFD significantly induced retinal leukostasis and breakdown of the blood–retina barrier in WT mice, but not in TKO mice. In parallel, HFD also induced retinal expression of adhesion molecules and cleaved IL-1β in WT mice, which were also abrogated in TKO mice. In culture, TXNIP overexpression induced NLRP3, IL-1β, and adhesion molecules expression, while TXNIP silencing inhibited them. Blocking the IL-1β receptor significantly suppressed TXNIP-induced expression of NLRP3-inflammasome and adhesion molecules in HREC. Ex-vivo assay showed that leukocytes isolated from WT-HFD, but not from TKO-HFD, induced leukostasis and cell death. At 18 weeks, HFD triggered development of degenerated (acellular) capillaries and decreased branching density in WT but not in TKO mice. Together, HFD-induced obesity triggered early retinal leukostasis and microvascular dysfunction at least in part via TXNIP-NLRP3-inflammasome activation. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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Review

Jump to: Editorial, Research

16 pages, 1000 KiB

Open AccessReview

Metabolic Syndrome and Male Fertility: Beyond Heart Consequences of a Complex Cardiometabolic Endocrinopathy

by Gianmaria Salvio, Alessandro Ciarloni, Melissa Cutini, Nicola delli Muti, Federica Finocchi, Michele Perrone, Silvia Rossi and Giancarlo Balercia

Int. J. Mol. Sci. 2022, 23(10), 5497; https://doi.org/10.3390/ijms23105497 - 14 May 2022

Cited by 17 | Viewed by 4899

Abstract

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). [...] Read more.

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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17 pages, 2343 KiB

Open AccessReview

Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease

by Melania Gaggini, Rudina Ndreu, Elena Michelucci, Silvia Rocchiccioli and Cristina Vassalle

Int. J. Mol. Sci. 2022, 23(5), 2719; https://doi.org/10.3390/ijms23052719 - 28 Feb 2022

Cited by 45 | Viewed by 6590

Abstract

Ceramides, composed of a sphingosine and a fatty acid, are bioactive lipid molecules involved in many key cellular pathways (e.g., apoptosis, oxidative stress and inflammation). There is much evidence on the relationship between ceramide species and cardiometabolic disease, especially in relationship with the [...] Read more.

Ceramides, composed of a sphingosine and a fatty acid, are bioactive lipid molecules involved in many key cellular pathways (e.g., apoptosis, oxidative stress and inflammation). There is much evidence on the relationship between ceramide species and cardiometabolic disease, especially in relationship with the onset and development of diabetes and acute and chronic coronary artery disease. This review reports available evidence on ceramide structure and generation, and discusses their role in cardiometabolic disease, as well as current translational chances and difficulties for ceramide application in the cardiometabolic clinical settings. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects 2.0)

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13 pages, 547 KiB

Open AccessReview

The Role of Resveratrol Administration in Human Obesity

by Laura M. Mongioì, Sandro La Vignera, Rossella Cannarella, Laura Cimino, Michele Compagnone, Rosita A. Condorelli and Aldo E. Calogero

Int. J. Mol. Sci. 2021, 22(9), 4362; https://doi.org/10.3390/ijms22094362 - 22 Apr 2021

Cited by 40 | Viewed by 4513

Abstract

Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great [...] Read more.

Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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26 pages, 1440 KiB

Open AccessReview

Oxidative Stress, Plant Natural Antioxidants, and Obesity

by Israel Pérez-Torres, Vicente Castrejón-Téllez, María Elena Soto, María Esther Rubio-Ruiz, Linaloe Manzano-Pech and Verónica Guarner-Lans

Int. J. Mol. Sci. 2021, 22(4), 1786; https://doi.org/10.3390/ijms22041786 - 11 Feb 2021

Cited by 214 | Viewed by 12620

Abstract

Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy [...] Read more.

Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite. This review discusses the participation of oxidative stress in obesity and the important groups of compounds found in plants with antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, and isoflavones), and curcuminoids (b) carotenoids, (c) capsaicinoids and casinoids, (d) isothiocyanates, (e) catechins, and (f) vitamins. Examples are analyzed, such as resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, and garlic. The antioxidant activities of these compounds depend on their activities as reactive oxygen species (ROS) scavengers and on their capacity to prevent the activation of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), and reduce the expression of target genes, including those participating in inflammation. We conclude that natural compounds have therapeutic potential for diseases mediated by oxidative stress, particularly obesity. Controlled and well-designed clinical trials are still necessary to better know the effects of these compounds. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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17 pages, 1037 KiB

Open AccessReview

Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

by Antonio Mancini, Carmine Bruno, Edoardo Vergani, Claudia d’Abate, Elena Giacchi and Andrea Silvestrini

Int. J. Mol. Sci. 2021, 22(4), 1667; https://doi.org/10.3390/ijms22041667 - 7 Feb 2021

Cited by 81 | Viewed by 10108

Abstract

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal [...] Read more.

The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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23 pages, 1374 KiB

Open AccessReview

Immunity as Cornerstone of Non-Alcoholic Fatty Liver Disease: The Contribution of Oxidative Stress in the Disease Progression

by Marcello Dallio, Moris Sangineto, Mario Romeo, Rosanna Villani, Antonino Davide Romano, Carmelina Loguercio, Gaetano Serviddio and Alessandro Federico

Int. J. Mol. Sci. 2021, 22(1), 436; https://doi.org/10.3390/ijms22010436 - 4 Jan 2021

Cited by 43 | Viewed by 6214

Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the major cause of chronic liver disease, especially in western countries. NAFLD encompasses a wide spectrum of hepatic histological alterations, from simple steatosis to steatohepatitis and cirrhosis [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the major cause of chronic liver disease, especially in western countries. NAFLD encompasses a wide spectrum of hepatic histological alterations, from simple steatosis to steatohepatitis and cirrhosis with a potential development of hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation and fibrosis. Several studies reported that insulin resistance, redox unbalance, inflammation, and lipid metabolism dysregulation are involved in NAFLD progression. However, the mechanisms beyond the evolution of simple steatosis to NASH are not clearly understood yet. Recent findings suggest that different oxidized products, such as lipids, cholesterol, aldehydes and other macromolecules could drive the inflammation onset. On the other hand, new evidence indicates innate and adaptive immunity activation as the driving force in establishing liver inflammation and fibrosis. In this review, we discuss how immunity, triggered by oxidative products and promoting in turn oxidative stress in a vicious cycle, fuels NAFLD progression. Furthermore, we explored the emerging importance of immune cell metabolism in determining inflammation, describing the potential application of trained immune discoveries in the NASH pathological context. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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9 pages, 221 KiB

Open AccessReview

Hyperhomocysteinemia: Focus on Endothelial Damage as a Cause of Erectile Dysfunction

by Gianmaria Salvio, Alessandro Ciarloni, Melissa Cutini and Giancarlo Balercia

Int. J. Mol. Sci. 2021, 22(1), 418; https://doi.org/10.3390/ijms22010418 - 3 Jan 2021

Cited by 20 | Viewed by 3948

Abstract

Erectile Dysfunction (ED) is defined as the inability to maintain and/or achieve a satisfactory erection. This condition can be influenced by the presence of atherosclerosis, a systemic pathology of the vessels that also affects the cavernous arteries and which can cause an alteration [...] Read more.

Erectile Dysfunction (ED) is defined as the inability to maintain and/or achieve a satisfactory erection. This condition can be influenced by the presence of atherosclerosis, a systemic pathology of the vessels that also affects the cavernous arteries and which can cause an alteration of blood flow at penile level. Among the cardiovascular risk factors affecting the genesis of atherosclerosis, hyperhomocysteinemia (HHcys) plays a central role, which is associated with oxidative stress and endothelial dysfunction. This review focuses on the biological processes that lead to homocysteine-induced endothelial damage and discusses the consequences of HHcys on male sexual function Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

13 pages, 259 KiB

Open AccessReview

Seminal Plasma Proteomic Biomarkers of Oxidative Stress

by Rossella Cannarella, Andrea Crafa, Federica Barbagallo, Laura M. Mongioì, Rosita A. Condorelli, Antonio Aversa, Aldo E. Calogero and Sandro La Vignera

Int. J. Mol. Sci. 2020, 21(23), 9113; https://doi.org/10.3390/ijms21239113 - 30 Nov 2020

Cited by 31 | Viewed by 2972

Abstract

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30–80% of cases. In recent years, seminal plasma [...] Read more.

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30–80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms “seminal fluid proteome”, “seminal plasma proteome”, “oxidative stress”, and “sperm oxidative stress” were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

14 pages, 1633 KiB

Open AccessReview

The Impact of Single- and Double-Strand DNA Breaks in Human Spermatozoa on Assisted Reproduction

by Ashok Agarwal, Cătălina Barbăroșie, Rafael Ambar and Renata Finelli

Int. J. Mol. Sci. 2020, 21(11), 3882; https://doi.org/10.3390/ijms21113882 - 29 May 2020

Cited by 55 | Viewed by 5177

Abstract

Several cellular insults can result in sperm DNA fragmentation either on one or both DNA strands. Oxidative damage, premature interruption of the apoptotic process and defects in DNA compaction during spermatogenesis are the main mechanisms that cause DNA breaks in sperm. The two-tailed [...] Read more.

Several cellular insults can result in sperm DNA fragmentation either on one or both DNA strands. Oxidative damage, premature interruption of the apoptotic process and defects in DNA compaction during spermatogenesis are the main mechanisms that cause DNA breaks in sperm. The two-tailed Comet assay is the only technique that can differentiate single- (SSBs) from double- (DSBs) strand DNA breaks. Increased levels of the phosphorylated isoform of the H2AX histone are directly correlated with DSBs and proposed as a molecular biomarker of DSBs. We have carried out a narrative review on the etiologies associated with SSBs and DSBs in sperm DNA, their association with reproductive outcomes and the mechanisms involved in their repair. Evidence suggests a stronger negative impact of DSBs on reproductive outcomes (fertilization, implantation, miscarriage, pregnancy, and live birth rates) than SSBs, which can be partially overcome by using intracytoplasmic sperm injection (ICSI). In sperm, SSBs are irreversible, whereas DSBs can be repaired by homologous recombination, non-homologous end joining (NHEJ) and alternative NHEJ pathways. Although few studies have been published, further research is warranted to provide a better understanding of the differential effects of sperm SSBs and DSBs on reproductive outcomes as well as the prognostic relevance of DNA breaks discrimination in clinical practice. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic and Endocrine Diseases: Basic and Translational Aspects)

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