Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and cytochrome P450 2E1-induced liver injury

Abstract

S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.

Figure 1

Structure of S-adenosyl-L-methionine (SAM), S-adenosylhomocysteine (SAH), and methionine and hepatic methionine metabolism. BHMT: Betaine homocysteine methyltransferase; CBS: Cystathionine β-synthase; GSH: Glutathione; MAT: Methionine adenosyltransferase; MS: Methionine synthase; MT: Methyltransferase; SAHH: SAH hydrolase; SAMDC: SAM decarboxylase.

Figure 2

Proposed mechanism by which SAM protects against CYP2e1-hepatotoxicity. ROS: Reactive oxygen species; CYP: Cytochrome P450; NF-κB: Nuclear factor κB; Nrf2: Nuclear factor erythroid 2-related factor 2.