Reduced levels of oxidative stress in methionine restricted F344 rats

Abstract

Dietary methionine restriction (MR) extends life span by 40‐50% in both rats and mice. Previous studies suggest that the anti‐aging properties of MR may be mediated, in part, by reduced oxidative stress. Our current objective was to determine the effect of MR on biomarkers of oxidative stress and endogenous antioxidants and related enzymes in the rat liver. Male F344 rats (6‐week old) were fed diets containing either 0.87% (control) or 0.17% (MR) methionine for up to 6 weeks. Five animals per group were sacrificed weekly and blood and liver were processed for analysis of glutathione (GSH), antioxidant enzymes and biomarkers of oxidative stress. In blood, levels of 8‐OHdG were 31% lower, 8‐isoporstane were 39% lower, and the levels of protein bound GSH were 24% lower in MR rats compared to controls indicating a reduction in levels of oxidative stress (p < 0.05). MR was also associated with 3‐ to 5‐fold reductions in glutathione peroxidase activity and a 2‐fold reduction in GSH levels in liver, where as, blood GSH levels were increased > 2‐fold (p < 0.01). Activity levels of glutathione reductase and superoxide dismutase were unchanged by MR. These results indicate that reductions in the levels of oxidative stress by MR are not mediated by increases in antioxidants and antioxidant related enzymes in liver but rather by decreased ROS production.