title: Realgar, cinnabar and An-Gong-Niu-Huang Wan are much less chronically nephrotoxic than common arsenicals and mercurials.
abstract: Realgar (As(4)S(4)) 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), HgCl(2) (0.118 mmol/kg, 1/10 of cinnabar), MeHg (0.012 mmol/kg, 1/100 of cinnabar), NaAsO(2) (As(3+) 0.028 mmol/kg, 1/100 of realgar) or Na(2)HAsO(4) (As(5+) 0.056 mmol/kg, 1/50 of realgar), daily for six weeks, and nephrotoxicity was examined. Animal body weights were decreased by MeHg and HgCl(2). Blood urea nitrogen and creatinine levels were elevated by MeHg. Renal pathology was severe in the MeHg and HgCl(2) groups, moderate in the arsenite, arsenate and realgar groups and mild in the cinnabar and AGNH groups. Renal Hg accumulation in the MeHg and HgCl(2) 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 HgCl(2). Expressions of cell adhesion gene S100a9 and E-cadherin were altered by HgCl(2), arsenite and realgar. Taken together, chemical forms of mercury and arsenic are major determinants in their disposition and toxicity.
authors.affiliation: Department of Pharmacology and Key Lab of Basic Pharmacology of Guizhou, Zunyi Medical College, Zunyi 563003.
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.forename: Jun-Wen
authors.initials: JW
authors.lastname: Yan
authors.forename: Jing-Zhen
authors.initials: JZ
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Shi
mesh_terms: D000818:Animals; D020261:Arsenic Poisoning / Q000473:pathology*; D001152:Arsenicals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D004032:Diet; D006651:Histocytochemistry; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology*; D017669:Mercury Compounds / Q000633:toxicity*; D008630:Mercury Poisoning / Q000473:pathology*; D051379:Mice; D008853:Microscopy; D010936:Plant Extracts / Q000633:toxicity*; D010946:Plants, Medicinal / Q000633:toxicity; D013440:Sulfides / Q000633:toxicity*
chemical_list: D001152:Arsenicals; D017669:Mercury Compounds; D010936:Plant Extracts; D013440:Sulfides; C058317:arsenic disulfide; D003404:Creatinine; C034211:cinnabar