Protective effects of S-adenosylmethionine against CCl4- and ethanol-induced experimental hepatic fibrosis

Zhang, F.; Gu, J.-X.; Zou, Xiaoping; Zhuge, Yuzheng

doi:10.1134/s0026893316020278

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…Different pathologic conditions leading to a decrease of the SAM cellular content are antagonized by the administration of exogenous SAM. Thus, SAM antagonizes rat liver damage induced by galactosamine [58] or acetaminophen [59] prevents the steatosis induced by ethanol in rats and mice [18][19][20]60,61]. These effects largely depend on the capacity of SAM to preserve an adequate GSH content and the transport of GSH into mitochondria [62,63].…”

Section: Sam Inhibitory Effectsmentioning

confidence: 99%

“…MATI/III downregulation, consequent to the oxidation of cysteine residue in the ATP binding site, and GSH fall occur in cirrhotic liver [17,18]. SAM administration reconstitutes the GSH pool, protects MATI/III [17,18], and inhibits liver fibrosis in rats and humans [2,[17][18][19][20][21]. Due to its inhibition by the reaction product, MATII upregulation does not compensate for MATI/III fall.…”

Section: The Methionine Adenosyltransferase Switchmentioning

confidence: 99%

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S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent

Pascale

Simile

Calvisi

et al. 2022

Cells

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Alterations of methionine cycle in steatohepatitis, cirrhosis, and hepatocellular carcinoma induce MAT1A decrease and MAT2A increase expressions with the consequent decrease of S-adenosyl-L-methionine (SAM). This causes non-alcoholic fatty liver disease (NAFLD). SAM administration antagonizes pathological conditions, including galactosamine, acetaminophen, and ethanol intoxications, characterized by decreased intracellular SAM. Positive therapeutic effects of SAM/vitamin E or SAM/ursodeoxycholic acid in animal models with NAFLD and intrahepatic cholestasis were not confirmed in humans. In in vitro experiments, SAM and betaine potentiate PegIFN-alpha-2a/2b plus ribavirin antiviral effects. SAM plus betaine improves early viral kinetics and increases interferon-stimulated gene expression in patients with viral hepatitis non-responders to pegIFNα/ribavirin. SAM prevents hepatic cirrhosis, induced by CCl4, inhibits experimental tumors growth and is proapoptotic for hepatocellular carcinoma and MCF-7 breast cancer cells. SAM plus Decitabine arrest cancer growth and potentiate doxorubicin effects on breast, head, and neck cancers. Furthermore, SAM enhances the antitumor effect of gemcitabine against pancreatic cancer cells, inhibits growth of human prostate cancer PC-3, colorectal cancer, and osteosarcoma LM-7 and MG-63 cell lines; increases genomic stability of SW480 cells. SAM reduces colorectal cancer progression and inhibits the proliferation of preneoplastic rat liver cells in vivo. The discrepancy between positive results of SAM treatment of experimental tumors and modest effects against human disease may depend on more advanced human disease stage at moment of diagnosis.

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Section: Sam Inhibitory Effectsmentioning

confidence: 99%

Section: The Methionine Adenosyltransferase Switchmentioning

confidence: 99%

S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent

Pascale

Simile

Calvisi

et al. 2022

Cells

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Peculiarities of Metabolic Changes in Experimental Animals at Early Terms of Pharmacological Correction of Toxic Liver Diseases

Timasheva

Каримов

Khusnutdinova

et al. 2020

Toksikologičeskij vestnik

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The paper presents the results of studies on metabolic changes in experimental animals with acute tetrachloromethane poisoning and further damage correction using substances possessing hepatoprotective properties: oxymethyluracil, ademethionine and ethylmethylhydroxypyridine succinate. It has been revealed that oxymethyluracil exhibits heteroprotective properties at the earliest stages of acute toxic liver damage with chemical toxicants: it has membrane-stabilizing properties, normalizes the levels of antioxidant system parameters, thereby restoring the oxidative-antioxidant balance in hepatocytes. Oxymethyluracil has more pronounced hepatoprotective properties at the early stages of treatment in comparison with ademethionine and ethylmethylhydroxypyridine succinate. The results obtained are important in terms of the prospective use of oxymethyluracil for the relief of hepatotoxic effects in acute exposure to hepatropic chemicals under environmental and industrial poisoning.

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Evaluation of the effectiveness of the use of hepatoprotector in acute liver damage by various toxicants in the experiment

Timasheva

Бакиров

Мухаммадиева

et al. 2021

Hygiene and Sanitation

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Introduction. Acute liver damage with ethanol and its surrogates and chemicals remains an urgent problem. Therefore, studies of the use of hepatoprotector in acute liver damage by various toxicants in the experiment are relevant. The purpose of this study is an experimental evaluation of the use of ademetionine in the early stages of the toxic effects of carbon tetrachloride and ethanol. Materials and methods. The therapeutic effect of the drug “Heptor” in acute intoxication with carbon tetrachloride (subcutaneous administration at a dose of 2 g/kg) and ethanol (oral administration at a dose of 4 g/kg weight) was studied. Studies of metabolic processes in the liver were carried out based on biochemical parameters of rat blood serum. Results. The studies showed that normalization of metabolic processes was observed after introducing “Heptor” against the background of exposure to both toxicants. The therapeutic effect of ademetionine in the case of carbon tetrachloride intoxication had a positive impact after 24 hours of administration and persisted after 72 hours of the experiment. These provisions were based on the results obtained: the restoration of the activity of marker enzymes of hepatocytes (AsAT, AlAT, LDH), the concentration of uric acid and cholesterol, and the indicators of protein metabolism were revealed. The introduction of ademetionine after ethanol intoxication helped restore the function of hepatocytes, which led to the normalization of protein metabolism. The drug stopped hyperenzymemia, which confirmed its membrane-protective properties. Conclusion. “Heptor” has a regenerating, detoxifying and membrane-protective effect in acute liver lesions with carbon tetrachloride and ethanol. The obtained data confirm the universality of this drug, based on the possibility of using various mechanisms of therapeutic action, which allows us to recommend ademetionine as a hepatoprotector to prevent early liver damage when exposed to high doses of multiple toxicants.

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Protective effects of S-adenosylmethionine against CCl4- and ethanol-induced experimental hepatic fibrosis

Cited by 3 publications

References 24 publications

S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent

S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent

Peculiarities of Metabolic Changes in Experimental Animals at Early Terms of Pharmacological Correction of Toxic Liver Diseases

Evaluation of the effectiveness of the use of hepatoprotector in acute liver damage by various toxicants in the experiment

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