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

As an endogenous gaseous mediator, H2 S exerts antioxidative, antiapoptotic, and cytoprotective effects in livers. This study was designed to investigate the protective role of H2 S against uranium-induced hepatotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2 S production was determined in livers. The levels of endogenous H2 S and H2 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 H2 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, H2 S synthesis capacity, and endogenous H2 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 H2 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 H2 S may be involved, at least in part, in inhibiting JNK signaling.