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Published on: June 28, 2024
Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat
Sreenivasa Maddineni1, Sailendra Nichenametla, Raghu Sinha
1Department of Comparative Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Abstract:
Lifelong dietary methionine restriction (MR) is associated with increased longevity and decreased incidence of age-related disorders and diseases in rats and mice. A reduction in the levels of oxidative stress may be a contributing mechanistic factor for the beneficial effects of MR. To examine this, we determined the effects of an 80% dietary restriction of Met on different biomarkers of oxidative stress and antioxidant pathways in blood, liver, kidney and brain in the rat. Male F-344 rats were fed control (0.86% methionine) or MR (0.17% methionine) diets for up to six months. Blood and tissues were analyzed for glutathione (GSH) concentrations, related enzyme activities and biomarkers of oxidative stress. MR was associated with reductions in oxidative stress biomarkers including plasma 8-hydoxydeoxyguanosine (8-OHdG) and 8-isoprostane and erythrocyte protein-bound glutathione after one month with levels remaining low for at least six months (P < 0.05). Levels of free GSH in blood were increased after 1-6 months of MR feeding whereas liver GSH levels were reduced over this time (P < 0.05). In MR rats, GSH peroxidase activity was decreased in liver and increased in kidney compared with controls. No changes in the activities of GSH reductase in liver and kidney and superoxide dismutase in liver were observed as a result of MR feeding. Altogether, these findings indicate that oxidative stress is reduced by MR feeding in rats, but this effect cannot be explained by changes in the activity of antioxidant enzymes.
Insights
Dietary methionine restriction (MR) in rats significantly reduces oxidative stress biomarkers, potentially contributing to longevity. However, these benefits are not solely explained by changes in antioxidant enzyme activity.
Area of Science:
- Gerontology
- Nutritional Biochemistry
- Oxidative Stress Research
Background:
- Lifelong dietary methionine restriction (MR) is linked to increased longevity and reduced age-related diseases in rodents.
- Reduced oxidative stress is a proposed mechanism underlying the health benefits of MR.
Purpose of the Study:
- To investigate the impact of an 80% dietary methionine restriction (MR) on oxidative stress biomarkers and antioxidant pathways in rats.
- To determine if reduced oxidative stress mediates the beneficial effects of MR.
Main Methods:
- Male F-344 rats were fed control (0.86% methionine) or MR (0.17% methionine) diets for up to six months.
- Blood and tissue samples (liver, kidney, brain) were analyzed for glutathione (GSH) levels, related enzyme activities, and oxidative stress markers like 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane.
Main Results:
- MR significantly reduced plasma 8-OHdG and 8-isoprostane, and erythrocyte protein-bound glutathione levels within one month, sustained for six months.
- Free blood GSH increased, while liver GSH decreased in MR rats.
- Glutathione peroxidase activity showed differential changes: decreased in the liver and increased in the kidney of MR rats.
Conclusions:
- Dietary methionine restriction effectively reduces oxidative stress in rats.
- The observed reduction in oxidative stress is not fully explained by alterations in the activity of key antioxidant enzymes like glutathione peroxidase, reductase, or superoxide dismutase.
