title: Hydrogen sulfide alleviates uranium-induced acute hepatotoxicity in rats: Role of antioxidant and antiapoptotic signaling.
abstract: As an endogenous gaseous mediator, H2S exerts antioxidative, antiapoptotic, and cytoprotective effects in livers. This study was designed to investigate the protective role of H2S against uranium-induced hepatotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2S production was determined in livers. The levels of endogenous H2S and H2S-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 H2S 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, H2S synthesis capacity, and endogenous H2S 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 H2S 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 H2S may be involved, at least in part, in inhibiting JNK signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 581-593, 2017.
authors.affiliation: Department of Biology, Institute of Biology, School of Pharmaceutical and Biological Science, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province, 421001, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Biology, Institute of Biology, School of Pharmaceutical and Biological Science, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province, 421001, People's Republic of China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Biology, Institute of Biology, School of Pharmaceutical and Biological Science, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province, 421001, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Institute of Neuroscience, Medical College, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province, 421001, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province, 421001, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013440:Sulfides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D013440:Sulfides; D051028:bcl-2-Associated X Protein; C005460:uranyl acetate; D045304:Cytochromes c; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; C025451:sodium bisulfide
keywords: apoptosis; hepatotoxicity; hydrogen sulfide; oxidative stress; uranium