title: The Tibetan medicine Zuotai differs from HgCl2 and MeHg in producing liver injury in mice.
abstract: Zuotai is composed mainly of β-HgS, while cinnabar mainly contains α-HgS. Both forms of HgS are used in traditional medicines and their safety is of concern. This study aimed to compare the hepatotoxicity potential of Zuotai and α-HgS with mercury chloride (HgCl2) and methylmercury (MeHg) in mice. Mice were orally administrated with Zuotai (30 mg/kg), α-HgS (HgS, 30 mg/kg), HgCl2 (33.6 mg/kg), or CH3HgCl (3.1 mg/kg) for 7 days, and liver injury and gene expressions related to toxicity, inflammation and Nrf2 were examined. Animal body weights were decreased by HgCl2 and to a less extent by MeHg. HgCl2 and MeHg produced spotted hepatocyte swelling and inflammation, while such lesions are mild in Zuotai and HgS-treated mice. Liver Hg contents reached 45-70 ng/mg in HgCl2 and MeHg groups; but only 1-2 ng/mg in Zuotai and HgS groups. HgCl2 and MeHg increased the expression of liver injury biomarker genes metallothionein-1 (MT-1) and heme oxygenase-1 (HO-1); the inflammation biomarkers early growth response gene (Egr1), glutathione S-transferase (Gst-mu), chemokine (mKC) and microphage inflammatory protein (MIP-2), while these changes were insignificant in Zuotai and HgS groups. However, all mercury compounds were able to increase the Nrf2 pathway genes
  quinone oxidoreductase 1 (Nqo1) and Glutamate-cysteine ligase, catalytic subunit (Gclc). In conclusion, the Tibetan medicine Zuotai and HgS are less hepatotoxic than HgCl2 and MeHg, and differ from HgCl2 and MeHg in hepatic Hg accumulation and toxicological responses.
authors.affiliation: Key Laboratory for Basic Pharmacology of Ministry of Health, Zunyi Medical College, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Key Laboratory for Basic Pharmacology of Ministry of Health, Zunyi Medical College, China.
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Li
authors.affiliation: Medical Research Center, Zunyi Medical College, Zunyi, China.
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Basic Pharmacology of Ministry of Health, Zunyi Medical College, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Li
authors.affiliation: Key Laboratory for Basic Pharmacology of Ministry of Health, Zunyi Medical College, China.
authors.forename: Ting-Wan
authors.initials: TW
authors.lastname: Xiong
authors.affiliation: Northwest Plateau Institute of Biology of Chinese Academy of Sciences, Xining, China.
authors.forename: Yi-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
authors.affiliation: Key Laboratory for Basic Pharmacology of Ministry of Health, Zunyi Medical College, China. Electronic address: JieLiu@zmc.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D038861:Medicine, Tibetan Traditional; D008627:Mercuric Chloride / Q000378:metabolism / Q000633:toxicity*; D017669:Mercury Compounds / Q000378:metabolism / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D017669:Mercury Compounds; D008767:Methylmercury Compounds; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C000615591:zuotai; D008627:Mercuric Chloride; C034211:cinnabar
keywords: Cinnabar; Electronmicrospy; Gene expression; Hepatotoxicity; Mercury chloride; MethylMercury; Nrf2; Zuotai