Hydrogen sulfide alleviates uranium-induced rat hepatocyte cytotoxicity via inhibiting Nox4/ROS/p38 MAPK pathway.

As a gasotransmitter, hydrogen sulfide (H S) plays a crucial role in regulating the signaling pathway mediated by oxidative stress. The purpose of this study was to investigate the protective effects of H S on uranium-induced rat hepatocyte cytotoxicity. Primary hepatocytes were isolated and cultured from Sprague Dawley rat liver tissues. After pretreating with sodium hydrosulfide (an H S donor) for 1 hour (or GKT-136901 for 30 minutes), hepatocytes were treated by uranyl acetate for 24 hours. Cell viability, reactive oxygen species (ROS), malondialdehyde (MDA), NADPH oxidase 4 (Nox4), and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation were respectively determined. The effects of direct inhibition of Nox4 expression by GKT-136901 (a Nox4 inhibitor) on ROS and phospho-p38 MAPK levels were examined in uranium-treated hepatocytes. The results implicate that H S can afford protection of rat hepatocytes against uranium-induced adverse effects through attenuating oxidative stress via prohibiting Nox4/ROS/p38 MAPK signaling.