Methionine supplementation accelerates oxidative stress and nuclear factor kappaB activation in livers of C57BL/6...

The present study was designed to investigate whether hyperhomocysteinemia (HHcy) induced by methionine supplementation promotes oxidative stress and nuclear factor kappaB (NFkappaB) activation in livers of C57BL/6 mice when fed a 2% methionine and low folate (1 mg/kg) diet for 12 weeks. Plasma homocysteine concentrations of mice fed methionine were found to be 49 micromol/L by 12 weeks of feeding, which was five times higher than that of controls. HHcy induced by methionine feeding significantly increased oxidative stress, as measured by thiobarbituric acid-reactive substances (P < .05) in livers. This was further confirmed by lower levels of hepatic glutathione (P < .05) and elevated mRNA expressions of hepatic antioxidative enzymes, such as Cu,Zn-superoxide dismutase, catalase, glutathione reductase, and L-gulonolactone oxidase in methionine-fed animals (P < .05). Hepatic function of mice fed methionine seems to be normal, while hepatic triglyceride concentration was lowered by methionine feeding. NFkappaB nuclear binding activities of livers were higher in the methionine group than in the control group. The above results suggest that HHcy induced by methionine may promote disturbances in lipid peroxidation and antioxidant processes and be a pro-inflammatory mediator in livers of C57BL/6 mice.