Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.

• Keywords
• Antioxidant enzyme, Catalytic activity, Expression, Glutathione, Metabolic dysfunction-associated steatotic liver disease,
• MeSH
• Antioxidants * metabolism   MeSH
• Liver metabolism   pathology   MeSH
• Humans MeSH
• Oxidative Stress drug effects   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Fatty Liver * metabolism   drug therapy   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antioxidants * MeSH
• Reactive Oxygen Species MeSH

Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance of therapeutic drugs, respectively. In the MASLD pathogenesis, dysregulated epigenetic mechanisms (e.g., histone modifications, DNA methylation, microRNAs) play a substantial role. In this study, the development of MASLD was investigated in mice fed a high-fat, high-fructose, and high-cholesterol (FFC) diet from 2 months of age, mice treated neonatally with monosodium glutamate (MSG) on a standard diet (STD), and mice treated with MSG on an FFC diet at 7 months of age and compared to control mice (C) on STD. Changes in liver histology, detoxification enzymes, epigenetic regulation, and genes involved in lipid metabolism were characterized and compared. The strong liver steatosis was observed in MSG STD, C FFC, and MSG FFC, with significant fibrosis in the latter one. Moreover, substantial alterations in hepatic lipid metabolism, epigenetic regulatory factors, and expressions and activities of various detoxification enzymes (namely superoxide dismutase, catalase, and carbonyl reductase 1) were observed in MASLD mice compared to control mice. miR-200b-3p, highly significantly upregulated in both FFC groups, could be considered as a potential diagnostic marker of MASLD. The MSG mice fed FFC seem to be a suitable model of MASLD characterized by both liver steatosis and fibrosis and substantial metabolic dysregulation.

• Keywords
• detoxification enzymes, high fat, fructose, and cholesterol (FFC) diet, metabolic dysfunction-associated steatotic liver disease (MASLD), miRNAs, mice, monosodium glutamate (MSG),
• Publication type
• Journal Article MeSH

PURPOSE: Consumption of dietary supplements with green tea extract (GTE) is popular for weight management, but it may be accompanied by various side effects, including interactions with drugs. The aim of the present in vivo study was to evaluate the effect of defined GTE (Polyphenon 60) in three dosage schemes on insulin, leptin and drug-metabolizing enzymes in obese mice. METHODS: Experimental obesity was induced by repeated s.c. application of monosodium glutamate to newborn mice. Green tea extract was administered in three dosage schemes in chow diet. The plasmatic levels of insulin and leptin were assayed using enzyme-linked immunosorbent assay. Enzyme activities and mRNA expressions of drug-metabolizing enzymes (totally 13) were analyzed in liver and small intestine using spectrophotometric and HPLC assays and RT-PCR, respectively. RESULTS: GTE-treatment decreased insulin and leptin levels. Eleven enzymes were significantly affected by GTE-treatment. Long-term administration of 0.01% GTE caused increase in the activity and mRNA level of cytochrome P450 3A4 (CYP3A4) ortholog in the liver as well as in the small intestine. Interestingly, short-term overdose by GTE (0.1%) had more pronounced effects on enzyme activities and mRNA expressions than long-term overdose. CONCLUSIONS: GTE-mediated induction of CYP3A4 ortholog, the main drug-metabolizing enzyme, could result in decreased efficacy of simultaneously or subsequently administered drug in obese individuals.

• Keywords
• Catechins, Drug-metabolizing enzymes, Green tea extract, Metabolic syndrome, Obesity,
• MeSH
• Antioxidants pharmacology   MeSH
• Aryl Hydrocarbon Hydroxylases genetics   metabolism   MeSH
• Tea chemistry   MeSH
• Cytochrome P-450 CYP2E1 genetics   metabolism   MeSH
• Cytochrome P-450 CYP3A genetics   metabolism   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Sodium Glutamate adverse effects   MeSH
• Insulin blood   MeSH
• Liver drug effects   metabolism   MeSH
• Leptin blood   MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Disease Models, Animal MeSH
• Mice, Obese MeSH
• Mice MeSH
• Obesity chemically induced   drug therapy   MeSH
• Dietary Supplements * MeSH
• Cytochrome P450 Family 2 MeSH
• Plant Extracts pharmacology   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antioxidants MeSH
• Aryl Hydrocarbon Hydroxylases MeSH
• Tea MeSH
• Cyp2a5 protein, mouse MeSH Browser
• Cytochrome P-450 CYP2E1 MeSH
• Cytochrome P-450 CYP3A MeSH
• cytochrome P450 3A4, mouse MeSH Browser
• Sodium Glutamate MeSH
• Insulin MeSH
• Leptin MeSH
• RNA, Messenger MeSH
• Cytochrome P450 Family 2 MeSH
• Plant Extracts MeSH