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Antioxidants
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Oxidative Stress in Liver Diseases
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Oxidative Stress in Liver Diseases

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 122409

Special Issue Editor

Prof. Dr. Greg Barritt

E-Mail Website
Guest Editor
Medical Biochemistry, College of Medicine and Public Health, Flinders University, G.P.O. Box 2100 Adelaide, South Australia
Interests: non-alcoholic fatty liver disease; paracetamol toxicity; regulation of hepatocyte metabolism; liver ischemia-reperfusion injury; TRPM2 calcium channels; intracellular calcium signaling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The generation of reactive oxygen species (ROS) and subsequent oxidative stress play central roles in both acute and chronic liver diseases, including drug toxicity, ischemia-reperfusion injury following liver surgery, alcoholic and non-alcoholic fatty liver disease, type 2 diabetes, and hepatocellular carcinoma. The role of pathological fat accumulation is of particular importance in the generation of ROS in non-alcoholic steatohepatitis and the promotion of hepatocellular carcinoma. Recent research has also highlighted the roles of intracellular calcium and calcium channels such as TRPM2, in the generation and actions of ROS in liver cells. Other research has focused on pathways involved in the removal of ROS, including heme oxygenase-1 and the Nrf2 pathway, and interventions that inhibit the production and/or actions of ROS. While considerable progress has been made, the mechanisms involved in both generating ROS and mediating the detrimental effects of ROS, and potential targets for pharmacological interventions, are still only partly understood.

We invite you to submit your latest research findings or a review to this Special Issue, which aims to bring together current knowledge of the mechanisms and pathways involved in the generation and action of ROS in the liver, and reports of potential pharmacological strategies for reduction in liver injury induced by ROS. We welcome submissions on any of these areas, and would be particularly interested in research on the roles of lipids, paracetamol, intracellular calcium, and reperfusion following ischemia in the generation of ROS; mechanisms of ROS-induced hepatocyte injury, especially in the progression of hepatocellular carcinoma; the roles of heme oxygenase-1 and the Nrf2 pathway in protecting against ROS damage; and mechanisms involved in the actions of re-purposed drugs and natural products such as resveratrol, curcumin, and silymarin in strategies to reduce ROS-induced liver injury. We believe that this Special Issue will offer a snapshot of current knowledge of the role of ROS in liver disease that will not only include important current advances, but will be a worthwhile resource for postgraduates and other researchers new to the area wishing to gain a reliable benchmark of current knowledge in this field.

We look forward to your contribution and will be very happy to discuss your suggestions.

Prof. Dr. Greg Barritt
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Liver disease
  • Fatty liver
  • Lipid peroxidation
  • Intracellular calcium
  • Ischemia reperfusion injury

Published Papers (22 papers)

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18 pages, 5106 KiB  
Article
Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress
by Dong-ha Kim, Yejin Sim, Jin-hyeon Hwang, In-Sook Kwun, Jae-Hwan Lim, Jihoon Kim, Jee-In Kim, Moon-Chang Baek, Mohammed Akbar, Wonhyo Seo, Do-Kyun Kim, Byoung-Joon Song and Young-Eun Cho
Antioxidants 2021, 10(9), 1386; https://doi.org/10.3390/antiox10091386 - 30 Aug 2021
Cited by 22 | Viewed by 4948
Abstract
Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the [...] Read more.
Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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17 pages, 2368 KiB  
Article
Oleoylethanolamide Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in High-Fat Diet-Fed Rats
by Anna Maria Giudetti, Daniele Vergara, Serena Longo, Marzia Friuli, Barbara Eramo, Stefano Tacconi, Marco Fidaleo, Luciana Dini, Adele Romano and Silvana Gaetani
Antioxidants 2021, 10(8), 1289; https://doi.org/10.3390/antiox10081289 - 14 Aug 2021
Cited by 14 | Viewed by 3685
Abstract
Long-term high-fat diet (HFD) consumption can cause weight gain and obesity, two conditions often associated with hepatic non-alcoholic fatty liver and oxidative stress. Oleoylethanolamide (OEA), a lipid compound produced by the intestine from oleic acid, has been associated with different beneficial effects in [...] Read more.
Long-term high-fat diet (HFD) consumption can cause weight gain and obesity, two conditions often associated with hepatic non-alcoholic fatty liver and oxidative stress. Oleoylethanolamide (OEA), a lipid compound produced by the intestine from oleic acid, has been associated with different beneficial effects in diet-induced obesity and hepatic steatosis. However, the role of OEA on hepatic oxidative stress has not been fully elucidated. In this study, we used a model of diet-induced obesity to study the possible antioxidant effect of OEA in the liver. In this model rats with free access to an HFD for 77 days developed obesity, steatosis, and hepatic oxidative stress, as compared to rats consuming a low-fat diet for the same period. Several parameters associated with oxidative stress were then measured after two weeks of OEA administration to diet-induced obese rats. We showed that OEA reduced, compared to HFD-fed rats, obesity, steatosis, and the plasma level of triacylglycerols and transaminases. Moreover, OEA decreased the amount of malondialdehyde and carbonylated proteins and restored the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, which decreased in the liver of HFD-fed rats. OEA had also an improving effect on parameters linked to endoplasmic reticulum stress, thus demonstrating a role in the homeostatic control of protein folding. Finally, we reported that OEA differently regulated the expression of two transcription factors involved in the control of lipid metabolism and antioxidant genes, namely nuclear factor erythroid-derived 2-related factor 1 (Nrf1) and Nrf2, thus suggesting, for the first time, new targets of the protective effect of OEA in the liver. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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15 pages, 2189 KiB  
Article
Enzyme-Treated Zizania latifolia Extract Protects against Alcohol-Induced Liver Injury by Regulating the NRF2 Pathway
by Bo Yoon Chang, Hyung Joong Kim, Tae Young Kim and Sung Yeon Kim
Antioxidants 2021, 10(6), 960; https://doi.org/10.3390/antiox10060960 - 15 Jun 2021
Cited by 11 | Viewed by 2590
Abstract
Binge drinking patterns easily produce a state of oxidative stress that disturbs liver function. Eventually, this leads to alcoholic liver disease. A safe and effective therapy for alcoholic liver disease remains elusive. Enzyme-treated Z. latifolia extract (ETZL) was studied as a potential agent [...] Read more.
Binge drinking patterns easily produce a state of oxidative stress that disturbs liver function. Eventually, this leads to alcoholic liver disease. A safe and effective therapy for alcoholic liver disease remains elusive. Enzyme-treated Z. latifolia extract (ETZL) was studied as a potential agent for treating alcohol-induced liver disease. In addition, its underlying mechanisms were elucidated. In the binge model, ETZL was pretreated with alcohol (5 g/kg) three times at 12-h intervals. Our results showed that ETZL pretreatment decreased the serum levels of ALT, AST, ALP, and TG. ETZL treatment appeared to prevent an increase in hepatic TG and MDA levels, and there was a decrease in total GSH following alcohol treatment. Histopathological examination showed that lipid droplets were significantly reduced in the ETZL group compared to the control group. ETZL also exhibited radical scavenging activity. It significantly reduced t-BHP-induced cytotoxicity and the production of reactive oxygen species (ROS) in HepG2 cells. ETZL also enhanced NRF2 nuclear translocation and increased expression of the downstream target genes HO-1, NQO1, and GCLC as an antioxidant defense. Finally, ETZL treatment significantly reduced cell death. Our study suggests that ETZL ameliorates binge ethanol-induced liver injury by upregulating the antioxidant defense mechanism. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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16 pages, 4988 KiB  
Article
Ameliorative Effects of Aspergillus awamori against the Initiation of Hepatocarcinogenesis Induced by Diethylnitrosamine in a Rat Model: Regulation of Cyp19 and p53 Gene Expression
by Doaa H. Assar, Abd-Allah A. Mokhbatly, Emad W. Ghazy, Amany E. Ragab, Samah Abou Asa, Walied Abdo, Zizy I. Elbialy, Nora Elbialy Mohamed and Ali H. El-Far
Antioxidants 2021, 10(6), 922; https://doi.org/10.3390/antiox10060922 - 7 Jun 2021
Cited by 14 | Viewed by 3228
Abstract
Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against [...] Read more.
Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against the initiation process of liver carcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats. Seventy-two male rats were divided equally into eight groups as follows, Group 1: untreated control; Group 2: DEN (200 mg/kg bw) intra-peritoneally for the initiation of HCC; Groups 3–5: DEN + ASP at a dose of 1, 0.5, and 0.25 mg/kg bw and groups 6–8: ASP at a dose of 1, 0.5, and 0.25 mg/kg bw. Supplementation of A. awamori significantly lightened the adverse impacts induced by DEN via restoring the leukogram to normal, lowering the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Furthermore, it enhanced the hepatic antioxidant capacity through increasing the reduced glutathione (GSH) level and catalase (CAT) activity with a marked reduction in malondialdehyde (MDA) level. In addition, it decreased the positive GST-P foci. Likewise, a significant alteration of DEN-associated hepatocarcinogenesis occurred through inhibiting cytochrome P450 (Cyp19) and activating p53 gene expression. In conclusion, supplementation of A. awamori counteracts the negative effects of DEN, inhibits the early development of GST-P-positive foci and could be used as a new alternative strategy for its chemo-preventive effect in liver cancer. To the best of our knowledge, the present study is the first to report the hepato-protective effect of A. awamori in induced hepatocarcinogenesis. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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18 pages, 3137 KiB  
Article
Aqueous Extract of Pepino Leaves Ameliorates Palmitic Acid-Induced Hepatocellular Lipotoxicity via Inhibition of Endoplasmic Reticulum Stress and Apoptosis
by Jen-Ying Hsu, Hui-Hsuan Lin, Charng-Cherng Chyau, Zhi-Hong Wang and Jing-Hsien Chen
Antioxidants 2021, 10(6), 903; https://doi.org/10.3390/antiox10060903 - 3 Jun 2021
Cited by 13 | Viewed by 3381
Abstract
Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the [...] Read more.
Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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19 pages, 4378 KiB  
Article
Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt, and CaMKKβ/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation
by Wen-Ping Jiang, Jeng-Shyan Deng, Shyh-Shyun Huang, Sheng-Hua Wu, Chin-Chu Chen, Jung-Chun Liao, Hung-Yi Chen, Hui-Yi Lin and Guan-Jhong Huang
Antioxidants 2021, 10(6), 897; https://doi.org/10.3390/antiox10060897 - 2 Jun 2021
Cited by 21 | Viewed by 3744
Abstract
Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before [...] Read more.
Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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18 pages, 5024 KiB  
Article
The Overactivation of NADPH Oxidase during Clonorchis sinensis Infection and the Exposure to N-Nitroso Compounds Promote Periductal Fibrosis
by Ji Hoon Jeong, Junyeong Yi, Myung Ki Hwang, Sung-Jong Hong, Woon-Mok Sohn, Tong-Soo Kim and Jhang Ho Pak
Antioxidants 2021, 10(6), 869; https://doi.org/10.3390/antiox10060869 - 28 May 2021
Cited by 4 | Viewed by 2671
Abstract
Clonorchis sinensis, a high-risk pathogenic human liver fluke, provokes various hepatobiliary complications, including epithelial hyperplasia, inflammation, periductal fibrosis, and even cholangiocarcinogenesis via direct contact with worms and their excretory–secretory products (ESPs). These pathological changes are strongly associated with persistent increases in free [...] Read more.
Clonorchis sinensis, a high-risk pathogenic human liver fluke, provokes various hepatobiliary complications, including epithelial hyperplasia, inflammation, periductal fibrosis, and even cholangiocarcinogenesis via direct contact with worms and their excretory–secretory products (ESPs). These pathological changes are strongly associated with persistent increases in free radical accumulation, leading to oxidative stress-mediated lesions. The present study investigated C. sinensis infection- and/or carcinogen N-nitrosodimethylamine (NDMA)-associated fibrosis in cell culture and animal models. The treatment of human cholangiocytes (H69 cells) with ESPs or/and NDMA increased reactive oxidative species (ROS) generation via the activation of NADPH oxidase (NOX), resulting in augmented expression of fibrosis-related proteins. These increased expressions were markedly attenuated by preincubation with a NOX inhibitor (diphenyleneiodonium chloride) or an antioxidant (N-acetylcysteine), indicating the involvement of excessive NOX-dependent ROS formation in periductal fibrosis. The immunoreactive NOX subunits, p47phox and p67phox, were observed in the livers of mice infected with C. sinensis and both infection plus NDMA, concomitant with collagen deposition and immunoreactive fibronectin elevation. Staining intensities are proportional to lesion severity and infection duration or/and NDMA administration. Thus, excessive ROS formation via NOX overactivation is a detrimental factor for fibrogenesis during liver fluke infection and exposure to N-nitroso compounds. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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12 pages, 1416 KiB  
Article
Peripheral Blood Mononuclear Cells Oxidative Stress and Plasma Inflammatory Biomarkers in Adults with Normal Weight, Overweight and Obesity
by Margalida Monserrat-Mesquida, Magdalena Quetglas-Llabrés, Cristina Bouzas, Xavier Capó, David Mateos, Lucía Ugarriza, Josep A. Tur and Antoni Sureda
Antioxidants 2021, 10(5), 813; https://doi.org/10.3390/antiox10050813 - 20 May 2021
Cited by 13 | Viewed by 3122
Abstract
Background: Obesity is an important pathology in public health worldwide. Obese patients are characterized by higher cardiovascular risk and a pro-inflammatory profile. Objective: To assess the oxidative stress in peripheral blood mononuclear cells (PBMCs) and inflammatory biomarkers in plasma in adults with normal [...] Read more.
Background: Obesity is an important pathology in public health worldwide. Obese patients are characterized by higher cardiovascular risk and a pro-inflammatory profile. Objective: To assess the oxidative stress in peripheral blood mononuclear cells (PBMCs) and inflammatory biomarkers in plasma in adults with normal weight, overweight and obesity. Methods: One hundred and fifty adults (55-80-years-old; 60% women) from the Balearic Islands, Spain, were recruited and classified according to body mass index (BMI). Anthropometric measurements were carried out, fasting blood samples were collected and plasma and PBMCs were obtained. Biochemical parameters, hemogram, antioxidant enzyme activities and protein levels, reactive oxygen species production (ROS), malondialdehyde (MDA), and cytokine (tumour necrosis factor, TNFα, and interleukin 6, IL-6) levels were measured. Results: Glycaemia, triglyceridemia, abdominal obesity, and waist-to-height ratio (WHtR) were higher, and HDL-cholesterol was lower in obese patients. MDA and TNFα plasma levels were higher in the obese compared to normal-weight group, while the levels of IL-6 were higher in both obese and overweight subjects with respect to normal-weight peers. The activities of all antioxidant enzymes in PBMCs as well as the production ROS progressively increased with BMI. The protein levels of catalase in PBMCs were higher in obese and glutathione reductase in obese and overweight subjects compared to normal-weight peers. No other differences were observed. Conclusion: The current results show that overweight and obesity are related to an increase in pro-oxidant and proinflammatory status in plasma and PBMCs. The studied biomarkers may be useful for monitoring the progression/reversal of obesity. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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15 pages, 3518 KiB  
Article
Lingonberry Improves Non-Alcoholic Fatty Liver Disease by Reducing Hepatic Lipid Accumulation, Oxidative Stress and Inflammatory Response
by Susara Madduma Hewage, Suvira Prashar, Karmin O and Yaw L. Siow
Antioxidants 2021, 10(4), 565; https://doi.org/10.3390/antiox10040565 - 6 Apr 2021
Cited by 17 | Viewed by 3927
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally and there is a pressing need for effective treatment. Lipotoxicity and oxidative stress are the important mediators in NAFLD pathogenesis. Lingonberry (Vaccinium vitis-idaea L.) is rich in anthocyanins that [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally and there is a pressing need for effective treatment. Lipotoxicity and oxidative stress are the important mediators in NAFLD pathogenesis. Lingonberry (Vaccinium vitis-idaea L.) is rich in anthocyanins that have antioxidant and anti-inflammatory properties. The present study investigated the effect of lingonberry supplementation on liver injury in C57BL/6J male mice fed a high-fat diet (HFD) for 12 weeks. Mice fed HFD displayed liver injury with steatosis, increased lipid peroxidation and inflammatory cytokine expression in the liver as compared to mice fed a control diet. Lingonberry supplementation for 12 weeks alleviated HFD-induced liver injury, attenuated hepatic lipid accumulation, and inflammatory cytokine expression. Lingonberry supplementation inhibited the expression of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-CoA carboxylase-1 (AAC-1) as well as activated AMP-activated protein kinase (AMPK) in the liver. It also decreased HFD-induced hepatic oxidative stress and aggregation of inflammatory foci. This was associated with a restoration of nuclear factor erythroid 2–related factor 2 (Nrf2) and glutathione level in the liver. These results suggest that lingonberry supplementation can protect against HFD-induced liver injury partly through attenuation of hepatic lipid accumulation, oxidative stress, and inflammatory response. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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13 pages, 2917 KiB  
Article
Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease
by Yi-Long Huang, Zhao-Qing Shen, Chen-Hua Huang, Yuan-Chi Teng, Chao-Hsiung Lin and Ting-Fen Tsai
Antioxidants 2021, 10(4), 559; https://doi.org/10.3390/antiox10040559 - 3 Apr 2021
Cited by 11 | Viewed by 3647
Abstract
Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are the most common chronic liver diseases worldwide. However, drugs to treat NAFLD and NASH are an unmet clinical need. This study sought to provide evidence that Cisd2 is a [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are the most common chronic liver diseases worldwide. However, drugs to treat NAFLD and NASH are an unmet clinical need. This study sought to provide evidence that Cisd2 is a molecular target for the development of treatments targeting NAFLD and NASH. Several discoveries are pinpointed. The first is that Cisd2 dosage modulates the severity of Western diet-induced (WD-induced) NAFLD. Specifically, Cisd2 haploinsufficiency accelerates NAFLD development and exacerbates progression toward NASH. Conversely, an enhanced Cisd2 copy number attenuates liver pathogenesis. Secondly, when a WD is fed to mice, transcriptomic analysis reveals that the major alterations affecting biological processes are related to inflammation, lipid metabolism, and DNA replication/repair. Thirdly, among these differentially expressed genes, the most significant changes involve Nrf2-mediated oxidative stress, cholesterol biosynthesis, and fatty acid metabolism. Finally, increased Cisd2 expression protects the liver from oxidative stress and reduces the occurrence of mitochondrial DNA deletions. Taken together, our mouse model reveals that Cisd2 plays a crucial role in protecting the liver from WD-induced damages. The development of therapeutic agents that effectively enhance Cisd2 expression is one potential approach to the treatment of WD-induced fatty liver diseases. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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14 pages, 5085 KiB  
Article
Protective Effects of Taraxacum officinale L. (Dandelion) Root Extract in Experimental Acute on Chronic Liver Failure
by Iulia Olimpia Pfingstgraf, Marian Taulescu, Raluca Maria Pop, Remus Orăsan, Laurian Vlase, Ana Uifalean, Doina Todea, Teodora Alexescu, Corina Toma and Alina Elena Pârvu
Antioxidants 2021, 10(4), 504; https://doi.org/10.3390/antiox10040504 - 24 Mar 2021
Cited by 31 | Viewed by 8350
Abstract
Background: Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root [...] Read more.
Background: Taraxacum officinale (TO) or dandelion has been frequently used to prevent or treat different liver diseases because of its rich composition in phytochemicals with demonstrated effect against hepatic injuries. This study aimed to investigate the possible preventing effect of ethanolic TO root extract (TOERE) on a rat experimental acute on chronic liver failure (ACLF) model. Methods: Chronic liver failure (CLF) was induced by human serum albumin, and ACLF was induced in CLF by D-galactosamine and lipopolysaccharide (D-Gal-LPS). Five groups (n = 5) of male Wistar rats (200–250 g) were used: ACLF, ACLF-silymarin (200 mg/kg b.w./day), three ACLF-TO administered in three doses (200 mg, 100 mg, 50 mg/kg b.w./day). Results: The in vivo results showed that treatment with TOERE administered in three chosen doses before ACLF induction reduced serum liver injury markers (AST, ALT, ALP, GGT, total bilirubin), renal tests (creatinine, urea), and oxidative stress tests (TOS, OSI, MDA, NO, 3NT). Histopathologically, TOERE diminished the level of liver tissue injury and 3NT immunoexpression. Conclusions: This paper indicated oxidative stress reduction as possible mechanisms for the hepatoprotective effect of TOERE in ACLF and provided evidence for the preventive treatment. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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18 pages, 3474 KiB  
Article
N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice
by Gunn-Guang Liou, Cheng-Chi Hsieh, Yi-Ju Lee, Pin-Hung Li, Ming-Shiun Tsai, Chi-Ting Li and Sue-Hong Wang
Antioxidants 2021, 10(3), 442; https://doi.org/10.3390/antiox10030442 - 12 Mar 2021
Cited by 10 | Viewed by 4377
Abstract
Acetaminophen (APAP) overdose induces acute liver damage and even death. The standard therapeutic dose of N-acetyl cysteine (NAC) cannot be applied to every patient, especially those with high-dose APAP poisoning. There is insufficient evidence to prove that increasing NAC dose can treat patients [...] Read more.
Acetaminophen (APAP) overdose induces acute liver damage and even death. The standard therapeutic dose of N-acetyl cysteine (NAC) cannot be applied to every patient, especially those with high-dose APAP poisoning. There is insufficient evidence to prove that increasing NAC dose can treat patients who failed in standard treatment. This study explores the toxicity of NAC overdose in both APAP poisoning and normal mice. Two inbred mouse strains with different sensitivities to propacetamol-induced hepatotoxicity (PIH) were treated with different NAC doses. NAC therapy decreased PIH by reducing lipid oxidation, protein nitration and inflammation, and increasing glutathione (GSH) levels and antioxidative enzyme activities. However, the therapeutic effects of NAC on PIH were dose-dependent from 125 (N125) to 275 mg/kg (N275). Elevated doses of NAC (400 and 800 mg/kg, N400 and N800) caused additional deaths in both propacetamol-treated and normal mice. N800 treatments significantly decreased hepatic GSH levels and induced inflammatory cytokines and hepatic microvesicular steatosis in both propacetamol-treated and normal mice. Furthermore, both N275 and N400 treatments decreased serum triglyceride (TG) and induced hepatic TG, whereas N800 treatment significantly increased interleukin-6, hepatic TG, and total cholesterol levels. In conclusion, NAC overdose induces hepatic and systemic inflammations and interferes with fatty acid metabolism. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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11 pages, 2052 KiB  
Article
Total Antioxidant Capacity in HBV Carriers, a Promising Biomarker for Evaluating Hepatic Fibrosis: A Pilot Study
by Jing-Hua Wang, Sung-Bae Lee, Dong-Soo Lee and Chang-Gue Son
Antioxidants 2021, 10(1), 77; https://doi.org/10.3390/antiox10010077 - 8 Jan 2021
Cited by 10 | Viewed by 2930
Abstract
Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity [...] Read more.
Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity and the extent of hepatic fibrosis, fifty-four subjects with liver fibrosis (5.5 ≤ liver stiffness measurement (LSM) score ≤ 16.0 kPa) by chronic hepatitis B virus (HBV) were analyzed. From the analysis of eight kinds of serum oxidative stress/antioxidant profiles and liver fibrosis degrees, the level of total antioxidant capacity (TAC) reflected a negative correlation with the severity of hepatic fibrosis (Pearson correlation, r = −0.35, p = 0.01). Moreover, TAC showed higher sensitivity (73.91%) than the aspartate transaminase (AST) to platelet ratio index (APRI, 56.52%) in the receiver operating characteristic (ROC) curves. Interestingly, the TAC level finely reflected the fibrosis degree in inactive carriers (HBV DNA < 2000 IU/mL), while the APRI did in active carriers (HBV DNA > 2000 IU/mL). In conclusion, TAC is a promising biomarker for evaluating the progression of liver fibrosis in patients with HBV, and this finding may indicate the involvement of TAC-composing factors in the pathogenesis of hepatic fibrosis in chronic HBV carriers. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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16 pages, 3960 KiB  
Article
Genistein Modulated Lipid Metabolism, Hepatic PPARγ, and Adiponectin Expression in Bilateral Ovariectomized Rats with Nonalcoholic Steatohepatitis (NASH)
by Sudaporn Pummoung, Duangporn Werawatganon, Maneerat Chayanupatkul, Naruemon Klaikeaw and Prasong Siriviriyakul
Antioxidants 2021, 10(1), 24; https://doi.org/10.3390/antiox10010024 - 29 Dec 2020
Cited by 15 | Viewed by 3214
Abstract
The aim of this study was to evaluate the protective effects of genistein on lipid accumulation and apoptosis in estrogen deficient rats with NASH. Female Sprague–Dawley rats (n = 48) were divided into ovariectomized (OVX) and non-OVX groups. Each group was then sub-divided [...] Read more.
The aim of this study was to evaluate the protective effects of genistein on lipid accumulation and apoptosis in estrogen deficient rats with NASH. Female Sprague–Dawley rats (n = 48) were divided into ovariectomized (OVX) and non-OVX groups. Each group was then sub-divided into 3 subgroups; control, NASH (rats fed with a high-fat, high-fructose (HFHF) diet), and NASH+Gen (rats fed with HFHF diet plus daily genistein at 16 mg/kg BW). Results showed that HFHF diet induced liver fat accumulation in both non-OVX and OVX rats, which was evidenced by hepatic steatosis on liver pathology and increased hepatic free fatty acid (FFA) and triglyceride levels. Hepatic fat accumulation was significantly more severe in NASH rats with OVX than non-OVX. Hepatocyte apoptosis was more severe in NASH groups compared with that in control groups. Genistein administration significantly improved histopathology of NASH in both non-OVX and OVX rats and attenuated hepatic lipid accumulation, oxidative stress, and hepatocyte apoptosis. Genistein also down-regulated PPARγ and up-regulated adiponectin expression. In summary, NASH could be worsened by estrogen deficiency, indicating the protective action of estrogen on NASH. Genistein administration alleviated hepatic steatosis and apoptosis through the down-regulation of PPARγ and up-regulation of adiponectin expression. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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14 pages, 5489 KiB  
Article
Oral Bisphenol A Worsens Liver Immune-Metabolic and Mitochondrial Dysfunction Induced by High-Fat Diet in Adult Mice: Cross-Talk between Oxidative Stress and Inflammasome Pathway
by Claudio Pirozzi, Adriano Lama, Chiara Annunziata, Gina Cavaliere, Clara Ruiz-Fernandez, Anna Monnolo, Federica Comella, Oreste Gualillo, Mariano Stornaiuolo, Maria Pina Mollica, Giuseppina Mattace Raso, Maria Carmela Ferrante and Rosaria Meli
Antioxidants 2020, 9(12), 1201; https://doi.org/10.3390/antiox9121201 - 30 Nov 2020
Cited by 22 | Viewed by 3704
Abstract
Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA’s worsening effect on several [...] Read more.
Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA’s worsening effect on several hepatic maladaptive processes associated to high-fat diet (HFD)-induced obesity in mice. After 12 weeks HFD feeding, C57Bl/6J male mice were exposed daily to BPA (50 μg/kg per os) along with HFD for 3 weeks. Glucose tolerance and lipid metabolism were examined in serum and/or liver. Hepatic oxidative damage (reactive oxygen species, malondialdehyde, antioxidant enzymes), and mitochondrial respiratory capacity were evaluated. Moreover, liver damage progression and inflammatory/immune response were determined by histological and molecular analysis. BPA amplified HFD-induced alteration of key factors involved in glucose and lipid metabolism, liver triglycerides accumulation, and worsened mitochondrial dysfunction by increasing oxidative stress and reducing antioxidant defense. The exacerbation by BPA of hepatic immune-metabolic dysfunction induced by HFD was shown by increased toll-like receptor-4 and its downstream pathways (i.e., NF-kB and NLRP3 inflammasome) amplifying inflammatory cytokine transcription and promoting fibrosis progression. This study evidences that BPA exposure represents an additional risk factor for the progression of fatty liver diseases strictly related to the cross-talk between oxidative stress and immune-metabolic impairment due to obesity. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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Review

Jump to: Research

36 pages, 1174 KiB  
Review
NADPH Oxidases Connecting Fatty Liver Disease, Insulin Resistance and Type 2 Diabetes: Current Knowledge and Therapeutic Outlook
by Alberto Nascè, Karim Gariani, François R. Jornayvaz and Ildiko Szanto
Antioxidants 2022, 11(6), 1131; https://doi.org/10.3390/antiox11061131 - 9 Jun 2022
Cited by 21 | Viewed by 3885
Abstract
Nonalcoholic fatty liver disease (NAFLD), characterized by ectopic fat accumulation in hepatocytes, is closely linked to insulin resistance and is the most frequent complication of type 2 diabetes mellitus (T2DM). One of the features connecting NAFLD, insulin resistance and T2DM is cellular oxidative [...] Read more.
Nonalcoholic fatty liver disease (NAFLD), characterized by ectopic fat accumulation in hepatocytes, is closely linked to insulin resistance and is the most frequent complication of type 2 diabetes mellitus (T2DM). One of the features connecting NAFLD, insulin resistance and T2DM is cellular oxidative stress. Oxidative stress refers to a redox imbalance due to an inequity between the capacity of production and the elimination of reactive oxygen species (ROS). One of the major cellular ROS sources is NADPH oxidase enzymes (NOX-es). In physiological conditions, NOX-es produce ROS purposefully in a timely and spatially regulated manner and are crucial regulators of various cellular events linked to metabolism, receptor signal transmission, proliferation and apoptosis. In contrast, dysregulated NOX-derived ROS production is related to the onset of diverse pathologies. This review provides a synopsis of current knowledge concerning NOX enzymes as connective elements between NAFLD, insulin resistance and T2DM and weighs their potential relevance as pharmacological targets to alleviate fatty liver disease. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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26 pages, 12614 KiB  
Review
TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species
by Eunus S. Ali, Grigori Y. Rychkov and Greg J. Barritt
Antioxidants 2021, 10(8), 1243; https://doi.org/10.3390/antiox10081243 - 3 Aug 2021
Cited by 17 | Viewed by 5031
Abstract
TRPM2 channels admit Ca2+ and Na+ across the plasma membrane and release Ca2+ and Zn2+ from lysosomes. Channel activation is initiated by reactive oxygen species (ROS), leading to a subsequent increase in ADP-ribose and the binding of ADP-ribose to [...] Read more.
TRPM2 channels admit Ca2+ and Na+ across the plasma membrane and release Ca2+ and Zn2+ from lysosomes. Channel activation is initiated by reactive oxygen species (ROS), leading to a subsequent increase in ADP-ribose and the binding of ADP-ribose to an allosteric site in the cytosolic NUDT9 homology domain. In many animal cell types, Ca2+ entry via TRPM2 channels mediates ROS-initiated cell injury and death. The aim of this review is to summarise the current knowledge of the roles of TRPM2 and Ca2+ in the initiation and progression of chronic liver diseases and acute liver injury. Studies to date provide evidence that TRPM2-mediated Ca2+ entry contributes to drug-induced liver toxicity, ischemia–reperfusion injury, and the progression of non-alcoholic fatty liver disease to cirrhosis, fibrosis, and hepatocellular carcinoma. Of particular current interest are the steps involved in the activation of TRPM2 in hepatocytes following an increase in ROS, the downstream pathways activated by the resultant increase in intracellular Ca2+, and the chronology of these events. An apparent contradiction exists between these roles of TRPM2 and the role identified for ROS-activated TRPM2 in heart muscle and in some other cell types in promoting Ca2+-activated mitochondrial ATP synthesis and cell survival. Inhibition of TRPM2 by curcumin and other “natural” compounds offers an attractive strategy for inhibiting ROS-induced liver cell injury. In conclusion, while it has been established that ROS-initiated activation of TRPM2 contributes to both acute and chronic liver injury, considerable further research is needed to elucidate the mechanisms involved, and the conditions under which pharmacological inhibition of TRPM2 can be an effective clinical strategy to reduce ROS-initiated liver injury. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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23 pages, 1421 KiB  
Review
Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism
by Guoyi Tang, Yu Xu, Cheng Zhang, Ning Wang, Huabin Li and Yibin Feng
Antioxidants 2021, 10(7), 1076; https://doi.org/10.3390/antiox10071076 - 5 Jul 2021
Cited by 61 | Viewed by 7325
Abstract
Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, [...] Read more.
Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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34 pages, 1028 KiB  
Review
Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice
by Marina Villanueva-Paz, Laura Morán, Nuria López-Alcántara, Cristiana Freixo, Raúl J. Andrade, M Isabel Lucena and Francisco Javier Cubero
Antioxidants 2021, 10(3), 390; https://doi.org/10.3390/antiox10030390 - 5 Mar 2021
Cited by 70 | Viewed by 9316
Abstract
Idiosyncratic drug-induced liver injury (DILI) is a type of hepatic injury caused by an uncommon drug adverse reaction that can develop to conditions spanning from asymptomatic liver laboratory abnormalities to acute liver failure (ALF) and death. The cellular and molecular mechanisms involved in [...] Read more.
Idiosyncratic drug-induced liver injury (DILI) is a type of hepatic injury caused by an uncommon drug adverse reaction that can develop to conditions spanning from asymptomatic liver laboratory abnormalities to acute liver failure (ALF) and death. The cellular and molecular mechanisms involved in DILI are poorly understood. Hepatocyte damage can be caused by the metabolic activation of chemically active intermediate metabolites that covalently bind to macromolecules (e.g., proteins, DNA), forming protein adducts—neoantigens—that lead to the generation of oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress, which can eventually lead to cell death. In parallel, damage-associated molecular patterns (DAMPs) stimulate the immune response, whereby inflammasomes play a pivotal role, and neoantigen presentation on specific human leukocyte antigen (HLA) molecules trigger the adaptive immune response. A wide array of antioxidant mechanisms exists to counterbalance the effect of oxidants, including glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), which are pivotal in detoxification. These get compromised during DILI, triggering an imbalance between oxidants and antioxidants defense systems, generating oxidative stress. As a result of exacerbated oxidative stress, several danger signals, including mitochondrial damage, cell death, and inflammatory markers, and microRNAs (miRNAs) related to extracellular vesicles (EVs) have already been reported as mechanistic biomarkers. Here, the status quo and the future directions in DILI are thoroughly discussed, with a special focus on the role of oxidative stress and the development of new biomarkers. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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39 pages, 3616 KiB  
Review
Changes in Glutathione Content in Liver Diseases: An Update
by Mariapia Vairetti, Laura Giuseppina Di Pasqua, Marta Cagna, Plinio Richelmi, Andrea Ferrigno and Clarissa Berardo
Antioxidants 2021, 10(3), 364; https://doi.org/10.3390/antiox10030364 - 28 Feb 2021
Cited by 106 | Viewed by 15155
Abstract
Glutathione (GSH), a tripeptide particularly concentrated in the liver, is the most important thiol reducing agent involved in the modulation of redox processes. It has also been demonstrated that GSH cannot be considered only as a mere free radical scavenger but that it [...] Read more.
Glutathione (GSH), a tripeptide particularly concentrated in the liver, is the most important thiol reducing agent involved in the modulation of redox processes. It has also been demonstrated that GSH cannot be considered only as a mere free radical scavenger but that it takes part in the network governing the choice between survival, necrosis and apoptosis as well as in altering the function of signal transduction and transcription factor molecules. The purpose of the present review is to provide an overview on the molecular biology of the GSH system; therefore, GSH synthesis, metabolism and regulation will be reviewed. The multiple GSH functions will be described, as well as the importance of GSH compartmentalization into distinct subcellular pools and inter-organ transfer. Furthermore, we will highlight the close relationship existing between GSH content and the pathogenesis of liver disease, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic cholestatic injury, ischemia/reperfusion damage, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatocellular carcinoma. Finally, the potential therapeutic benefits of GSH and GSH-related medications, will be described for each liver disorder taken into account. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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24 pages, 3048 KiB  
Review
Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy
by Johanna C. Arroyave-Ospina, Zongmei Wu, Yana Geng and Han Moshage
Antioxidants 2021, 10(2), 174; https://doi.org/10.3390/antiox10020174 - 26 Jan 2021
Cited by 207 | Viewed by 13179
Abstract
Oxidative stress (OxS) is considered a major factor in the pathophysiology of inflammatory chronic liver diseases, including non-alcoholic liver disease (NAFLD). Chronic impairment of lipid metabolism is closely related to alterations of the oxidant/antioxidant balance, which affect metabolism-related organelles, leading to cellular lipotoxicity, [...] Read more.
Oxidative stress (OxS) is considered a major factor in the pathophysiology of inflammatory chronic liver diseases, including non-alcoholic liver disease (NAFLD). Chronic impairment of lipid metabolism is closely related to alterations of the oxidant/antioxidant balance, which affect metabolism-related organelles, leading to cellular lipotoxicity, lipid peroxidation, chronic endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Increased OxS also triggers hepatocytes stress pathways, leading to inflammation and fibrogenesis, contributing to the progression of non-alcoholic steatohepatitis (NASH). The antioxidant response, regulated by the Nrf2/ARE pathway, is a key component in this process and counteracts oxidative stress-induced damage, contributing to the restoration of normal lipid metabolism. Therefore, modulation of the antioxidant response emerges as an interesting target to prevent NAFLD development and progression. This review highlights the link between disturbed lipid metabolism and oxidative stress in the context of NAFLD. In addition, emerging potential therapies based on antioxidant effects and their likely molecular targets are discussed. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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15 pages, 710 KiB  
Review
Radical Response: Effects of Heat Stress-Induced Oxidative Stress on Lipid Metabolism in the Avian Liver
by Nima K. Emami, Usuk Jung, Brynn Voy and Sami Dridi
Antioxidants 2021, 10(1), 35; https://doi.org/10.3390/antiox10010035 - 30 Dec 2020
Cited by 91 | Viewed by 8083
Abstract
Lipid metabolism in avian species places unique demands on the liver in comparison to most mammals. The avian liver synthesizes the vast majority of fatty acids that provide energy and support cell membrane synthesis throughout the bird. Egg production intensifies demands to the [...] Read more.
Lipid metabolism in avian species places unique demands on the liver in comparison to most mammals. The avian liver synthesizes the vast majority of fatty acids that provide energy and support cell membrane synthesis throughout the bird. Egg production intensifies demands to the liver as hepatic lipids are needed to create the yolk. The enzymatic reactions that underlie de novo lipogenesis are energetically demanding and require a precise balance of vitamins and cofactors to proceed efficiently. External stressors such as overnutrition or nutrient deficiency can disrupt this balance and compromise the liver’s ability to support metabolic needs. Heat stress is an increasingly prevalent environmental factor that impairs lipid metabolism in the avian liver. The effects of heat stress-induced oxidative stress on hepatic lipid metabolism are of particular concern in modern commercial chickens due to the threat to global poultry production. Chickens are highly vulnerable to heat stress because of their limited capacity to dissipate heat, high metabolic activity, high internal body temperature, and narrow zone of thermal tolerance. Modern lines of both broiler (meat-type) and layer (egg-type) chickens are especially sensitive to heat stress because of the high rates of mitochondrial metabolism. While this oxidative metabolism supports growth and egg production, it also yields oxidative stress that can damage mitochondria, cellular membranes and proteins, making the birds more vulnerable to other stressors in the environment. Studies to date indicate that oxidative and heat stress interact to disrupt hepatic lipid metabolism and compromise performance and well-being in both broilers and layers. The purpose of this review is to summarize the impact of heat stress-induced oxidative stress on lipid metabolism in the avian liver. Recent advances that shed light on molecular mechanisms and potential nutritional/managerial strategies to counteract the negative effects of heat stress-induced oxidative stress to the avian liver are also integrated. Full article
(This article belongs to the Special Issue Oxidative Stress in Liver Diseases)
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