Methylsulfonylmethane relieves cobalt chloride-induced hypoxic toxicity in C2C12 myoblasts

In biology and medicine, hypoxia refers to reduced oxygen tension or oxygen starvation resulting from various environmental or pathological conditions. Prolonged hypoxia may lead to an imbalance in protein production and a loss of muscle mass in animals. The physiological response to hypoxia includes oxidative stress-induced activation of complex cell-signaling networks such as hypoxia-inducible factor (HIF), phosphoinositide 3-kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK-STAT). Methylsulfonylmethane (MSM) is a natural sulfur compound that regulates HIF-1α expression and provides cytoprotection from oxidative stress. In this study, we explored the anti-hypoxic activity and cytoprotective effect of MSM in cobalt chloride (CoCl₂)-induced hypoxic C2C12 mouse myoblast culture.

We used western blotting, real time PCR, flow cytometry for molecular signaling studies and we also used MTT assay and ChIP assay along with comet assay for cellular processes.

MSM prevented the CoCl₂ induced cytotoxicity. Molecular markers of hypoxia, induced by CoCl₂, were normalized or reduced by MSM, which also inhibited the effect of CoCl₂-induced JAK2/STAT5b/Cyclin D1 and PI3K/AKT signaling. CoCl₂-induced oxidative stress results in activation of the NRF2/HO-1-mediated cell survival pathway and inhibition of DNA repair, both of which were prevented by MSM.

We suggest MSM can be considered as a candidate drug for reducing the effects of hypoxia in both animals and humans.