IBS008738, a TAZ activator, facilitates muscle repair and inhibits muscle injury in a mouse model of sport-induced injury.

High-intensity exercise can cause excessive generation of ROS and induce oxidative stress injury in the body, which is a major reason accounting for muscle damage following exercise. The previous study demonstrated that IBS008738, the activator of TZA, was able to enhance myogenesis in mouse myogenic C2C12 cells, prevent dexamethasone-induced muscle atrophy, and facilitate muscle repair in cardiotoxin-induced muscle injury. Accordingly, our study was designed to probe into the potential role of IBS008738 in muscle damage in mouse models induced by high-intensity exercise. Mice were first administrated with IBS008738, and then subjected to high-intensity eccentric exercise to induce muscle damage after 24 h. During the experiment, mouse weight change and food take were recorded. At the end of the experiment, blood samples were collected through cardiac puncture and centrifugated. Serum levels of blood urea nitrogen (BUN), creatinine, glucose, lactate dehydrogenase (LDH), creatinine kinase (CK), and C-related protein were evaluated using an autoanalyzer. After mice were sacrificed, the gastrocnemius muscles were dissected for DCFH-DA assay of ROS generation, thiobarbituric acid-reactive substances (TBARS) assay of MDA content, hematoxylin-eosin (H&E) staining of histological examination, and western blotting analysis of Akt/mTOR/S6K1 signaling expression. IBS008738 and/or exercise exert significant effects on mouse weight and food take. High-intensity exercise markedly increased ROS generation and lipid peroxidation, upregulated serum levels of CK, LDH, and C-related protein, ameliorated muscle histological damage, and reduced TAZ, phosphorylated (p)-Akt, p-mTOR, and p-S6K1 protein levels in mice. However, IBS008738 administration reversed the above changes induced by high-intensity exercise in mice. IBS008738 alleviates oxidative stress and muscle damage in mice after high-intensity exercise by activating TAZ and the Akt/mTOR/S6K1 signaling pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-024-00667-6.