title: Mercury sulfides are much less nephrotoxic than mercury chloride and methylmercury in mice.
abstract: Mercury sulfides (α-HgS, β-HgS) are frequently included in traditional medicines. Mercury is known for nephrotoxicity, their safety is of concern. To address this question, mice were orally administrated with Zuotai (54% β-HgS, 30mg/kg), α-HgS (HgS, 30mg/kg), HgCl2(33.6mg/kg), or MeHgCl (3.1mg/kg) for 7days, and nephrotoxicity was examined. Animal body weights were decreased by HgCl2and to a lesser extent by MeHg, but unaltered after Zuotai and HgS. HgCl2and MeHg produced renal tubular vacuolation, interstitial inflammation and cell degeneration with protein cysts in the tubular lumen, while these pathological lesions were mild in Zuotai and HgS-treated mice. Electron microscopy showed that HgCl2and MeHg produced spotted swelling endothelium reticulum, while these lesions were mild or absent in Zuotai and HgS-treated mice. Renal Hg contents reached 250-300ng/mg kidney in HgCl2and MeHg groups as compared to 2-3ng/mg in Zuotai and HgS groups. The expression of kidney injury biomarkers, kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (Ngal), were increased after HgCl2and MeHg, but unaltered after Zuotai and HgS. The expression of renal influx transporters Oat3 and Oatp4c1 was decreased, while the expression of renal efflux transporter such as Mrp2, Mrp4, and Mate2 was increased following HgCl2and MeHg. These gene expressions were unchanged after Zuotai and HgS. In summary, both α-HgS and β-HgS are less nephrotoxic than HgCl2and MeHg, indicating that chemical forms of mercury are a major determinant of mercury disposition and toxicity.
authors.affiliation: Zunyi Medical College, Zunyi, China. Electronic address: Jieliu@zmc.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Zunyi Medical College, Zunyi, China.
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Zunyi Medical College, Zunyi, China.
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Li
authors.affiliation: Zunyi Medical College, Zunyi, China.
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Zhou
authors.affiliation: Zunyi Medical College, Zunyi, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Li
authors.affiliation: Zunyi Medical College, Zunyi, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Northwest Plateau Institute of biology of Chinese Academy of Sciences, Xining, China.
authors.forename: Cen
authors.initials: C
authors.lastname: Li
authors.affiliation: Northwest Plateau Institute of biology of Chinese Academy of Sciences, Xining, China.
authors.forename: Yu-Zhi
authors.initials: YZ
authors.lastname: Du
authors.affiliation: Northwest Plateau Institute of biology of Chinese Academy of Sciences, Xining, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wei
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology; D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D000071068:Lipocalin-2 / Q000378:metabolism; D008627:Mercuric Chloride / Q000633:toxicity*; D008628:Mercury / Q000378:metabolism; D017669:Mercury Compounds / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D009929:Organ Size / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D000071068:Lipocalin-2; D017669:Mercury Compounds; D008767:Methylmercury Compounds; C071332:Lcn2 protein, mouse; D008627:Mercuric Chloride; D008628:Mercury; C034211:cinnabar
keywords: Electromicrospy; Kim-1; Mercury chloride; Mercury sulfides; Methylmercury; Mrp2; Nephrotoxicity; Oatp4c1; Renal Hg; Renal transporter