Semaglutide attenuates excessive exercise-induced myocardial injury through inhibiting oxidative stress and inflammation in rats.

AIMS: To investigate the protective effects and mechanism of semaglutide on exercise-induced myocardial injury. MAIN METHODS: Effects of semaglutide on lipopolysaccharide (LPS)-induced oxidative stress injuries and inflammatory response were assessed in H9c2 cell via MTT assay and Western blot. Quiet control group, over training group and three doses of semaglutide treated overtraining groups were subjected to the swimming training with increasing load for consecutive 10 weeks. Immediately after the last training, the body weight, myocardial morphological changes, injury markers and inflammatory response related proteins of the model rats were analyzed. KEY FINDINGS: Semaglutide at three concentrations in LPS treated H9c2 cells significantly increased the survival rate and inhibited the apoptosis of cardiomyocytes. Moreover, semaglutide activated AMPK pathway, improve autophagy and inhibited reactive oxygen species production in LPS treated H9C2 cells. In vivo results further revealed that chronic treatment of semaglutide induced significant increase in myocardial injury markers. The pathological histology analysis results showed that semaglutide ameliorated myocardial morphological changes, reduced area of lipid accumulation and significantly decreased the expression levels of NF-κB, TNF-α and IL-1β. SIGNIFICANCE: Semaglutide exert the protective effects on exercise-induced cardiomyopathy by activating AMPK pathway, increasing autophagy, reducing the production of ROS and inflammation-related proteins.