Hydrogen sulfide alleviates uranium‐induced acute hepatotoxicity in rats: Role of antioxidant and antiapoptotic signaling

Abstract

As an endogenous gaseous mediator, H S exerts antioxidative, antiapoptotic, and cytoprotective effects in livers. This study was designed to investigate the protective role of H S against uranium-induced hepatotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H S production was determined in livers. The levels of endogenous H S and H S-producing enzymes (CBS and CSE) were measured in liver homogenates from uranium -intoxicated rats. In rats injected intraperitoneally (i.p.) with uranyl acetate or NaHS (an H S donor) alone or in combination, we examined biochemical parameters to assess liver function, revealed hepatic histopathological alteration, investigated oxidative stress markers, and explored apoptotic signaling in liver homogenates. The results suggest that uranium-intoxication in rats decreased CBS and CSE protein expression, H S synthesis capacity, and endogenous H S generation. NaHS administration in uranium-intoxicated rats produced amelioration in liver biochemical indices and histopathological effects, decreased MDA content, and increased GSH level and antioxidative enzymes activities like SOD, CAT, GPx, and GST. NaHS administration in uranium-intoxicated rats attenuated uranium-activated phosphorylation state of JNK. NaHS treatment in uranium-intoxicated rats increased antiapoptotic Bcl-2 but decreased pro-apoptotic Bax, resulting in the rise of Bcl-2/Bax ratio. NaHS treatment in uranium-intoxicated rats reduced the apoptosis mediator caspase-3 and cytochrome c release and elevated ATP contents. Taken together, these data implicate that H S can afford protection to rat livers against uranium-induced adverse effects mediated by up-regulation of antioxidant and antiapoptotic signaling. The anti-apoptotic property of H S may be involved, at least in part, in inhibiting JNK signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 581-593, 2017.

Medical gases for stroke therapy: summary of progress 2015–2016

“…H 2 S is a signaling molecule and exert antioxidant, anti-inflammatory and vasodilatory actions 474849. These results lend credence to the notion that H 2 S provide neuroprotection in ischemic brain tissue.…”

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

“…H 2 S alleviated acetaminophen or carbon tetrachloride‐induced rat hepatotoxicity by anti‐inflammation and antioxidation . Recently, our work suggests that H 2 S attenuated uranium‐induced acute rat hepatotoxicity through antioxidant and antiapoptotic signaling . As a widely recognized potential antioxidant, H 2 S is demonstrated to directly scavenge ROS.…”

“…Thus, antioxidation may be one of the major targets of prevention and treatment of hepatotoxicity induced by uranium. Our recent study indicates that H 2 S protected uranium‐induced rat liver injury by increasing the activities of antioxidases and promoting the synthesis of antioxidant glutathione, which could improve the cellular antioxidant capacity . In this study, NaHS administration declined ROS and MDA contents in uranium‐induced hepatocytes, which attenuated oxidative stress and subsequently reversed uranium‐induced hepatocyte cytotoxicity.…”

“…Sodium hydrosulfide (NaHS), GKT‐136901, and 2′,7′‐dichlorofluorescein diacetate (DCFH‐DA) were purchased from Sigma (NY). Uranyl and NaHS solutions were prepared according to our recent report . GKT‐136901 was dissolved in 1% dimethyl sulfoxide, 0.5% carboxymethyl cellulose, and 0.25% polysorbate 20 according to the previously published protocols .…”

“…[10,11] Recently, our work suggests that H 2 S attenuated uranium-induced acute rat hepatotoxicity through antioxidant and antiapoptotic signaling. [12] As a widely recognized potential antioxidant, H 2 S is demonstrated to directly scavenge ROS.…”