Long-term consumption of a methionine-supplemented diet increases iron and lipid peroxide levels in rat liver

Methionine is a protective factor against various types of liver damage, but excessive dietary methionine is hepatotoxic. Because the mechanisms of L-methionine-related hepatotoxicity are poorly understood, the effect of long-term excessive L-methionine intake on the metabolism of iron and antioxidants was studied in rat liver to determine whether oxidative stress is involved. Wistar male rats were fed either an L-methionine-supplemented (16.0 g/kg) diet or a control diet for 1, 3, 6 and 9 mo. The growth rate of L-methionine-supplemented rats was significantly slower than that of controls. Iron, ferritin and thiobarbituric acid-reactive substances (TBARS) levels in the liver were greater in supplemented rats than in controls. Serum iron and transferrin levels were significantly lower in L-methionine-treated rats compared with controls. Serum ferritin did not differ between the two groups. Hepatic glutathione peroxidase activity, catalase activity and total glutathione concentrations were higher in rats fed the L-methionine-supplemented diet at 1 and 3 mo, but not at 6 and 9 mo. These results indicate that long-term consumption of excess L-methionine by rats may affect primarily iron metabolism rather than the antioxidant defense system and, consequently, induce an accumulation of iron.