Glutathione Protects Against Exercise‐Induced Oxidative Stress In Mature db/db Mice Hearts

Abstract

Low‐intensity exercise improves cardiac antioxidants in young animals irrespective of metabolic changes in type 2 diabetes (T2D). As diabetes and aging synergistically can decrease antioxidants, if exercises can increase antioxidants in mature T2D hearts, is unknown. 8‐month old db/db and wild‐type (WT) mice were moderately exercised for 3 weeks, and cardiac redox regulation was evaluated. Without altering metabolic status, exercise increased cardiac antioxidants and attenuated stress in mature WT mice. In contrast, exercise in db/db mice worsened oxidative damage, which was not explained by superoxide dismutase or catalase activities. Instead, loss of the antioxidant, glutathione (GSH) was noted. Further, GSH biosynthesis [γ‐glutamylcysteine synthase] and recycling [NADPH/NADP, glutathione reductase] were impaired while GSH‐dependent stress (GPX, 4‐hydroxynonenal, TGF‐β) was increased in these hearts. To validate the causal role for GSH, exercising db/db mice were administered exogenous GSH, which attenuated cardiac damage. This study shows that unlike younger animals, short‐term exercise may induce oxidative stress in mature animals and GSH supplementation can inhibit such stress in these hearts. Therefore, recent assertions of detrimental impact of antioxidants during exercise in healthy individuals should be extrapolated with caution in mature T2D patients undergoing exercise.