Effects of creatine monohydrate supplementation on liver mineral antioxidant protection in rats submitted to high-intensity interval training (HIIT)

Abstract

Abstract Creatine monohydrate supplementation is commonly combined with exercise training to promote muscle hypertrophy and enhance performance. This study investigated the effects of creatine monohydrate supplementation on hepatic markers of tissue damage, lipoperoxidation intensity, and enzymatic antioxidant cofactor levels in healthy rats submitted to high-intensity interval training (HIIT). Male Wistar rats were assigned to four groups: sedentary control (C), sedentary creatine supplementation (Cr), HIIT (HT), and HIIT combined with creatine supplementation (HTC). The C and HT groups received standard commercial chow, whereas the Cr and HTC groups received a diet supplemented with 2% creatine. The HT and HTC groups also completed a 12-week treadmill HIIT protocol. After the intervention, biochemical profile, serum liver function markers, and hepatic morphology were analyzed. Malondialdehyde (MDA) levels were assessed as a marker of lipoperoxidation, while hepatic Cu, Mn, Zn, and Se levels were measured as antioxidant cofactors using spectrophotometry. Results were analyzed using two-way ANOVA followed by appropriate post hoc tests. HIIT was associated with greater running distance and maximal speed than the sedentary condition. Creatine supplementation increased alkaline phosphatase levels, whereas HIIT increased serum creatinine and reduced serum triacylglycerol levels. In the liver, HIIT increased MDA and decreased selenium levels independently of creatine supplementation. These changes were not accompanied by histopathological evidence of hepatic damage. In conclusion, HIIT induced lipoperoxidation that was not counterbalanced by enzymatic antioxidant processes related to Cu, Mn, Zn, and Se cofactors, resulting in relative hepatic antioxidant imbalance without tissue damage. Creatine supplementation did not modify the effects of exercise training on the liver.