Induction of hepatic glutathione synthesis via alterations in sulfur amino acid metabolism in mice treated with silymarin acutely

Abstract

It has been known that silymarin exhibits protective effects against chemical‐induced liver injury, but the underlying mechanism of its beneficial action remains unclear. We examined the silymarin‐induced changes in the metabolism of sulfur‐containing amino acids in association with its effects on antioxidant capacity of liver. Male mice were treated with silymarin (100 or 200 mg/kg, po) every 12 hr for a total of 3 doses. Hepatic methionine level was increased, but the activity and protein expression of methionine adenosyltransferase were decreased dose‐dependently in liver of the mice treated with silymarin. S‐Adenosylmethionine or homocysteine was not altered whereas cystathionine, cysteine and glutathione (GSH) were increased significantly. Betaine‐homocysteine methyltransferase and cysteine dioxygenase were down‐regulated, but cystathionine β‐synthase was induced. γ‐Glutamylcysteine synthetase was unchanged by silymarin treatment. Oxygen radical scavenging capacity of liver cytosol against peroxyl radical and peroxynitrite was increased, and hepatic lipid peroxidation was diminished in the silymarin‐treated mice. It is concluded that silymarin enhances hepatic GSH biosynthesis by elevating cysteine availability via increment in cysteine synthesis and inhibition of its catabolism to taurine, which may subsequently contribute to the antioxidant defense of liver.