Ferrostatin-1 alleviates the damage of C2C12 myoblast and mouse pelvic floor muscle induced by mechanical trauma

Abstract

Abstract Ferroptosis is a special form of regulated cell death, which is reported to play an important role in a variety of traumatic diseases by promoting lipid peroxidation and devastating cell membrane structure. PFD is a kind of disease affecting the quality and health of many women’s lives, which is closely related to the injury of the pelvic floor muscles. It has been clinically discovered that there is anomalous oxidative damage in the pelvic floor muscles of female patients with PFD, but the specific mechanism is still unclear. In this study, we explored the relationship between ferroptosis and mechanical stretch-induced pelvic floor muscle injury, whether obesity would make the muscles more susceptible to ferroptosis. Our results, in vitro, showed that mechanical stretch could induce oxidative damage to myoblasts and trigger ferroptosis. In addition, GPX4 and 15LOX-1 showed significant changes coinciding with ferroptosis, which was much more obvious in PA-treated myoblasts. Furthermore, ferroptosis induced by mechanical stretch could be rescued by ferroptosis inhibitor (ferrostatin-1). More importantly, in vivo, we found that the mitochondria of pelvic floor muscle shrank, which were consistent with the mitochondrial morphology of ferroptosis, and GPX4 and 15LOX-1 showed the same change observed in cells. In conclusion, our data indicate the intimate relationship between ferroptosis and mechanical injury of pelvic floor muscle, and provide a novel insight for PFD therapy.