Fibrosis Development Linked to Alterations in Glucose and Energy Metabolism and Prooxidant–Antioxidant Balance in Experimental Models of Liver Injury

Semenovich, D.S.; Andrianova, N.V.; Zorova, L.D.; Pevzner, I.B.; Abramicheva, P.A.; Elchaninov, A.V.; Markova, O.V.; Petrukhina, A.S.; Zorov, D.B.; Plotnikov, E.Y.

Авторы: Semenovich Dmitry S., Andrianova Nadezda V., Zorova Ljubava D., Pevzner Irina B., Abramicheva Polina A., Elchaninov Andrey V., Markova Olga V., Petrukhina Aleksandra S., Zorov Dmitry B., Plotnikov Egor Y.
Журнал: ANTIOXIDANTS
Том: 12
Номер: 8
Год издания: 2023
Номер статьи: 1604
DOI: 10.3390/antiox12081604
Аннотация: The development of liver fibrosis is one of the most severe and life-threatening outcomes of chronic liver disease (CLD). For targeted therapy of CLD, it is highly needed to reveal molecular targets for normalizing metabolic processes impaired in damaged liver and associated with fibrosis. In this study, we investigated the morphological and biochemical changes in rat liver models of fibrosis induced by chronic administration of thioacetamide, carbon tetrachloride, bile duct ligation (BDL), and ischemia/reperfusion (I/R), with a specific focus on carbohydrate and energy metabolism. Changes in the levels of substrates and products, as well as enzyme activities of the major glucose metabolic pathways (glycolysis, glucuronidation, and pentose phosphate pathway) were examined in rat liver tissue after injury. We examined key markers of oxidative energy metabolism, such as the activity of the Krebs cycle enzymes, and assessed mitochondrial respiratory activity. In addition, pro- and anti-oxidative status was assessed in fibrotic liver tissue. We found that 6 weeks of exposure to thioacetamide, carbon tetrachloride, BDL or I/R resulted in a decrease in the activity of glycolytic enzymes, retardation of mitochondrial respiration, elevation of glucuronidation, and activation of pentose phosphate pathways, accompanied by a decrease in antioxidant activity and the onset of oxidative stress in rat liver. Resemblance and differences in the changes in the fibrosis models used are described, including energy metabolism alterations and antioxidant status in the used fibrosis models. The least pronounced changes in glucose metabolism and mitochondrial functions in the I/R and thioacetamide models were associated with the least advanced fibrosis. Ultimately, liver fibrosis significantly altered the metabolic profile in liver tissue and the flux of glucose metabolic pathways, which could be the basis for targeted therapy of liver fibrosis in CLD caused by toxic, cholestatic, or I/R liver injury.Keywords: liver fibrosis; bile duct ligation; hepatic ischemia; glycolysis; Krebs cycle; mitochondrial respiration; oxidative stress; glutathione; metabolism
Добавил в систему: Семенович Дмитрий Сергеевич

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Fibrosis Development Linked to Alterations in Glucose and Energy Metabolism and Prooxidant–Antioxidant Balance in Experimental Models of Liver Injuryстатья

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