The Preclinical Study Exploring the Effects of Creatine Supplementation on Renal Antioxidant Enzymes Following Doxorubicin Treatment

Introduction: Doxorubicin is an effective chemotherapy drug, but its use is limited by its cytotoxicity. One of doxorubicin’s anticancer mechanisms is generation of reactive oxygen species which may lead to oxidative stress. The kidney, however, is very vulnerable to oxidative stress, and one way to manage oxidative stress is to scavenge reactive oxygen species via antioxidant enzymes. Although doxorubicin-induced oxidative stress has been extensively studied, a viable treatment to attenuate doxorubcin side effects has yet to be found. This study investigated the effect of creatine feeding on catalase, glutathione peroxide, and superoxide dismutase-1 expression in the kidney following doxorubicin treatment. Methods: Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups, control saline (C+SAL, n=7), control doxorubicin (C+DOX, n=7), creatine saline (Cr+SAL, n=6) and creatine doxorubicin (Cr+DOX, n=8). Control groups were fed normal chow, and creatine groups were fed chow supplemented with 3% creatine. After two weeks of feeding, doxorubicin groups received15 mg/kg doxorubicin whereas saline groups received saline as a placebo. Western blotting was used to access antioxidant enzyme expression in renal tissue. Results: A significant between group difference was observed with catalase expression, but post hoc testing did not reveal where differences existed. A trend existed toward doxorubicin treatment increasing catalase expression and creatine attenuated this trend. Glutathione peroxidase and superoxide dismutase-1 presented a similar profile as catalase; however, no significant between group differences were observed. There was a trend, however, toward increased expression of glutathione peroxidase and superoxide dismutase-1 in doxorubicin-treated animals that seemed to be attenuated with creatine supplementation. Conclusion: To our knowledge there are no studies exploring the antioxidant properties of creatine supplementation in the kidney with doxorubicin, and it is possible that creatine may enhance antioxidant properties that can attenuate the negative effects doxorubicin in the kidney. A trend towards antioxidant enzyme normalization promoted by creatine with doxorubicin suggests that creatine might have similar effect to that observed in previous studies using antioxidant drugs.