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Lu Y.-F.,Zunyi Medical College | Lu Y.-F.,Shanghai University of Traditional Chinese Medicine | Wu Q.,Zunyi Medical College | Yan J.-W.,Zunyi Medical College | And 5 more authors.
Experimental Biology and Medicine

Realgar (As4S4) and cinnabar (HgS) are frequently included in traditional Chinese medicines and Indian Ayurvedic medicines. Both As and Hg are well known for toxic effects, and their safety is of concern. The aim of this study was to compare chronic nephrotoxicity of An-Gong-Niu-Huang Wan (AGNH), realgar and cinnabar with common arsenicals and mercurials. Mice were orally administrated with AGNH (3 g/kg, 6-fold of clinical dose), cinnabar (0.3 g/kg, amount in AGNH) and realgar (0.3 g/kg, amount in AGNH), HgCl2 (0.118 mmol/kg, 1/10 of cinnabar), MeHg (0.012 mmol/kg, 1/100 of cinnabar), NaAsO2 (As3+ 0.028 mmol/kg, 1/100 of realgar) or Na 2HAsO4 (As5+ 0.056 mmol/kg, 1/50 of realgar), daily for six weeks, and nephrotoxicity was examined. Animal body weights were decreased by MeHg and HgCl2. Blood urea nitrogen and creatinine levels were elevated by MeHg. Renal pathology was severe in the MeHg and HgCl2 groups, moderate in the arsenite, arsenate and realgar groups and mild in the cinnabar and AGNH groups. Renal Hg accumulation in the MeHg and HgCl2 groups was 50-200 folds higher than the cinnabar group. Expressions of metallothionein-1 and heme oxygenase-1, biomarkers for metal toxicity, were increased 2-5 folds by arsenite, arsenate, MeHg and HgCl 2, but not by realgar, cinnabar and AGNH. The chemokine and glutathione-S transferase-α4, markers for inflammation, were also increased by MeHg and HgCl2. Expressions of cell adhesion gene S100a9 and E-cadherin were altered by HgCl2, arsenite and realgar. Taken together, chemical forms of mercury and arsenic are major determinants in their disposition and toxicity. Copyright © 2011 by the Society for Experimental Biology and Medicine. Source

Yang H.,Expertmental Center Basic Medical Laboratory | Peng F.,Guiyang Traditional Medical College | Liu J.,Zunyi Medical College | Wu Q.,Zunyi Medical College | Shi J.-Z.,Expertmental Center Basic Medical Laboratory
Chinese Journal of Pharmacology and Toxicology

OBJECTIVE: To explore effect of cinnabar and cinnabar-containing Zhusha Anshenwan on cytochrome P450 (CYP) mRNA in liver of rats. METHODS: Adult Sprague-Dawley rats were gavaged with Zhusha Anshenwan 1.4 g·kg -1, cinnabar 0.15 g·kg-1, HgS 0.15 g·kg -1, HgCl20.02 g·kg-1, once daily, for 21 d, and liver toxicity was determined by measuring body mass gain. Liver index, alanine transaminase (ALT) ativity, mercury accumulation in liver and mRNA levels of metalloehionein-2 ( MT-2), CYP1A, CYP3A2, CYP4A10, CYP2B1 and constitute androstane receptor (CAR) genes were detected with RT-PCR. RESULTS: Compared with normal control group, body mass gain retarded in HgCl2 group with a reduced food intake and activities. A significant accumulation of Hg in livers in HgCl2 group was evident, however these changes were not evident in cinnabar, Zhusha Anshenwan and HgS groups. Compared with normal control group, mRNA expressions of MT-2, CYP1A1, CYP1A2 were evidently higher and CAR were apparently lower in HgCl2 group. Compared with nromal control group, accumulation of Hg, liver index, ALT, MT-2, CYP1A1, CYP1A2 and CYP4A10 CAR, CYP2B1 mRNA in cinnabar, Zhusha Anshenwan and HgS groups were unaltered, except that CYP3A2 mRNA expression obviously increased in cinnabar group. CONCLUSION: Zhusha Anshenwan, cinnabar, and HgS accumulate much less mercury in the liver than HgCl2 at clinical dose for 3 weeks. MT-2, CAR and cytochrome P450 genes are altered in HgCl2 group, CYP3A2 mRNA increase in cinnabar group, but all of above are not changed in Zhusha Anshenwan and HgS groups. Source

Kang F.,Guiyang Traditional Medical College | Wu K.,Guiyang Traditional Medical College | He H.,Guiyang Traditional Medical College | Wu Q.,Zunyi Medical College | And 3 more authors.
Zhongguo Zhongyao Zazhi

Objective: To study the toxicity of Cinnabar and Cinnabar-containing traditional medicines (Zhusha Anshenwan) comparable to common mercurials. Method: The toxicity of methylmercury (MeHg), mercuric chloride (HgCl 2), Cinnabar and Zhusha Anshenwan was studied in cultured human liver HL-7702 cells and in mice following acute and subacute exposures. Result: The 50% lethal concentrations (LC50) of MeHg, HgCl2, Cinnabar and Zhusha Anshenwan in human liver HL-7702 cells were 4.4, 9.2, 2 460, 4 050 mg · L-1, respectively. Oral cinnabar at a dose of 20 g · kg-1 (clinical dosage 250 times) did not kill mouse, but no mouse could survive MeHg at a dose of 0.1 g · kg-1 or HgCl 2 at a dose of 0.15 g · kg-1. Subacute toxicity experiment indicated that HgCl2 retarded body weight gain with significant accumulation of Hg in the liver and kidney. In comparison, mercury accumulation after Cinnabar and Zhusha Anshenwan was insignificant. No apparent hepatic and renal dysfunctions were evident under the experimental conditions, but the metallothionein-2 mRNA levels were much higher in HgCl2 group than in other groups. Conclusion: Cinnabar and Zhusha Anshenwan are much less toxic than MeHg and HgCl2. Source

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