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

Abstract

As a gasotransmitter, hydrogen sulfide (H2S) 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 2S 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 2S 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 2S can afford protection of rat hepatocytes against uranium‐induced adverse effects through attenuating oxidative stress via prohibiting Nox4/ROS/p38 MAPK signaling.

Targeting Hydrogen Sulfide Modulates Dexamethasone-Induced Muscle Atrophy and Microvascular Rarefaction, through Inhibition of NOX4 and Induction of MGF, M2 Macrophages and Endothelial Progenitors

“…This is consistent with previous findings in other organs and models; endogenous H2S was found to inhibit NOX4-provoked oxidative stress in LPS-induced macrophages [ 43 ]. H2S alleviated uranium-induced rat hepatocyte cytotoxicity via inhibiting the Nox4/ROS/p38 MAPK pathway [ 44 ]. H2S reduced ischemia and reperfusion injury in neuronal cells of the retina through the modulation of transcription factor NF-kappa B and the reduction in retinal inflammation [ 45 ].…”

Role of apigenin in high glucose-induced retinal microvascular endothelial cell dysfunction via regulating NOX4/p38 MAPK pathway in vitro

“…In addition, NOX4 overexpression as achieved by transfection with pc-NOX4 (Figure 4B). As NOX4 is a crucial upstream modulator of p38 MAPK signaling [21] , the p38 MAPK signaling was examined. As presented in Figure 4C, the protein expression of p-p38 was remarkably elevated following HG exposure, which was inhibited by Api (10 μmol/L) treatment; however, this inhibition was partially abolished when NOX4 was over-expressed.…”

“…Api exerted an inhibitory effect on NOX4 expression, and the protection of Api against HG-induced endothelial cell damages was partially reversed by NOX4 overexpression, indicating that Api might exert its functions partly through downregulating NOX4 expression. Furthermore, it is well documented that NOX4 is a crucial upstream modulator of p38 MAPK signaling [21] . p38 MAPK signaling can be activated by numerous cellular stresses, such as hypoxic and oxidative stresses, and regulate multiple extracellularly stimulated processes.…”

Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival

“…Improving cell tolerance to increased Ca 2+ /P i concentrations can lead to a broader and enhanced therapeutic window by limiting the cytotoxic effects of high concentration Ca 2+ /P i . One promising option to mitigate ion-mediated toxicity is hydrogen sulfide (H 2 S), a gasotransmitter simple signaling molecule [17] that has been found capable of suppressing oxidative stress in mitochondria [18][19][20] as well as MSC survival and proliferation under high stress conditions like hypoxia, oxidative stress, and serum deprivation [21,22]. Unfortunately, there are only a few H 2 S donors commercially available, with most research having to employ the burst release kinetics achieved by sodium hydrosulfide (NaHS) or sodium sulfide (Na 2 S) [23].…”