Low-intensity pulsed ultrasound alleviates exhaustive exercise-induced oxidative skeletal muscle damage through GsMTx4-sensitive mechanosensitive channel-associated Nrf2/HO-1 signaling

Low-intensity pulsed ultrasound (LIPUS) is a non-invasive mechanical stimulation modality with potential effects on tissue repair and mechanotransduction. However, whether LIPUS protects against exhaustive exercise-induced oxidative skeletal muscle damage through mechanosensitive channel-associated antioxidant signaling remains unclear. In this study, male Sprague-Dawley rats were subjected to an exhaustive swimming exercise protocol and treated with LIPUS, with or without GsMTx4, a broad inhibitor of mechanosensitive ion channels. Exercise performance, serum biochemical indicators, tissue oxidative stress, glycogen storage, skeletal muscle histology, and molecular markers related to mechanosensitive channel-associated Nrf2/HO-1 signaling were evaluated. LIPUS improved swimming exhaustion time, reduced serum markers of tissue injury, attenuated lipid peroxidation, increased SOD activity, preserved hepatic and skeletal muscle glycogen content, and improved skeletal muscle histological integrity. These protective effects were accompanied by increased Piezo1 and HO-1 expression and enhanced Nrf2 nuclear accumulation. GsMTx4 partially attenuated the LIPUS-associated improvements in exercise endurance, oxidative stress, glycogen preservation, histological injury, and Nrf2/HO-1 signaling. These findings suggest that LIPUS alleviates exhaustive exercise-induced oxidative muscle damage, at least in part, through GsMTx4-sensitive mechanosensitive channel-associated Nrf2/HO-1 antioxidant signaling. Because GsMTx4 is not Piezo1-specific, further genetic and electrophysiological studies are required to confirm the precise mechanosensitive channel subtype involved.