Topiroxostat confers protections against lipopolysaccharide-induced myocardial Injury

Previous studies have validated the organ protective effects of topiroxostat, a selective xanthine oxidase inhibitor indicated for the management of hyperuricemia and gout. Now, a recent study published in the Journal of Surgical Research has reported that the treatment helps in attenuating lipopolysaccharide (LPS)-induced myocardial injury via suppression of apoptosis and oxidative stress.

The study carried out by a team of Chinese researchers measured the hemodynamic parameters, myocardial injury marker enzymes, oxidative stress, myocardial injury, and apoptosis in endotoxemic shock model rats treated with topiroxostat. The in vitro experiments also evaluated the effect of topiroxostat on cell vitality, oxidative stress, inflammatory factors, and apoptosis-related markers.

The study findings showed that the topiroxostat treatment contributed to significant improvement in myocardial dysfunction and superoxide dismutase activity. However, the levels of lactate dehydrogenase, creatine kinase and malondialdehyde were found to be suppressed in endotoxemic shock rat models. The treatment also improved the dry-wet weight ratios of the hearts in rats. The topiroxostat treatment also helped to reduce interstitial edema and apoptosis in myocardial tissues. The drug pretreatment contributed to increased lipopolysaccharide (LPS)-induced H9c2 cell vitality and reduce oxidative stress and inflammation. Down-regulation of apoptosis-related markers, p-p65, and p-p65/p65 levels in LPS-induced H9c2 cells was also observed following treatment.

The present study provides the first evidence on the potential use of topiroxostat to prevent myocardial injury induced by LPS. The mechanism associated with the protective effect is conferred via inhibition of mitochondrial oxidative stress, inflammation, and antiapoptosis.

Reference: Liu J, Zhang X, Lao Y, et al. Protective Effect of Topiroxostat on Myocardial Injury Induced by Lipopolysaccharide. J Surg Res. 2022;271:171-179.