title: Hydrogen sulfide (H2S) attenuates uranium-induced acute nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways.
abstract: As an endogenous gaseous mediator, H2S exerts anti-oxidative, anti-inflammatory and cytoprotective effects in kidneys. This study was designed to investigate the protective effect of H2S against uranium-induced nephrotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2S formation was explored in kidneys. The levels of endogenous H2S and H2S-producing enzymes (CBS and CSE) were measured in renal homogenates from rats intoxicated by an intraperitoneally (i.p.) injection of uranyl acetate at a single dose of 2.5, 5 or 10 mg/kg. In rats injected i.p. with uranyl acetate (5 mg/kg) or NaHS (an H2S donor, 28 or 56 μmol/kg) alone or in combination, we determined biochemical parameters and histopathological alteration to assess kidney function, examined oxidative stress markers, and investigated Nrf2 and NF-κB pathways in kidney homogenates. The results suggest that uranium intoxication in rats decreased endogenous H2S generation as well as CBS and CSE protein expression. NaHS administration in uranium-intoxicated rats ameliorated the renal biochemical indices and histopathological effects, lowered MDA accumulation, and restored GSH level and anti-oxidative enzymes activities like SOD, CAT, GPx and GST. NaHS treatment in uranium-intoxicated rats activated uranium-inhibited protein expression and nuclear translocation of transcription factor Nrf2, which increased protein expression of downstream target-Nrf2 genes HO-1, NQO-1, GCLC, and TXNRD-1. NaHS administration in uranium-intoxicated rats inhibited uranium-induced nuclear translocation and phosphorylation of transcription factor κB/p65, which decreased protein expression of target-p65 inflammatory genes TNF-α, iNOS, and COX-2. Taken together, these data implicate that H2S can afford protection to rat kidneys against uranium-induced adverse effects through induction of antioxidant defense by activating Nrf2 pathway and reduction of inflammatory response by suppressing NF-κB pathway.
authors.affiliation: Institute of Biology, Pharmacy and Life College, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province 421001, PR China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Institute of Biology, Pharmacy and Life College, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province 421001, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Institute of Biology, Pharmacy and Life College, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province 421001, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
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, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Changsheng West Road 28, Hengyang City, Hunan Province 421001, PR China. Electronic address: xiaoqingtang@outlook.com.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014501:Uranium / Q000633:toxicity*
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D014501:Uranium; D006862:Hydrogen Sulfide
keywords: Hydrogen sulfide (H(2)S); NF-κB; Nephrotoxicity; Nrf2; Oxidative stress; Uranium