title: Realgar- and cinnabar-containing an-gong-niu-huang wan (AGNH) is much less acutely toxic than sodium arsenite and mercuric chloride.
abstract: An-gong-niu-huang wan (AGNH) is a famous traditional Chinese medicine used for brain trauma, hemorrhage, and coma. AGNH contains 10% realgar (As₄S₄) and 10% cinnabar (HgS). Both As and Hg are well-known for their toxic effects, and the safety of AGNH is of concern. To address this question, the acute toxicity of AGNH, realgar and cinnabar were compared to sodium arsenite (NaAsO₂) and mercuric chloride (HgCl₂). Mice were administrated orally AGNH at 1, 3 and 6g/kg. AGNH at 3g/kg contains 2.8mmol As/kg as realgar and 1.18mmol Hg/kg as cinnabar. Realgar, cinnabar, arsenite (0.28 mmol/kg, 10% of realgar) and HgCl₂ (0.256 mmol/kg, 20% of cinnabar) were orally given to mice for comparison. Blood and tissues were collected 8h later for toxicity evaluation. Serum alanine aminotransferase was increased by arsenite and blood urea nitrogen was increased by HgCl₂. Total As accumulation after arsenite in liver (100-fold) and kidney (13-fold) was much higher than that after realgar. The accumulation of Hg after HgCl₂ in liver was 400-fold higher and kidney 30-fold higher than after cinnabar. Histopathology showed moderate liver and kidney injuries after arsenite and HgCl₂, but injuries were mild or absent after AGNH, realgar, and cinnabar. The expression of metallothionein-1, a biomarker of metal exposure, was increased 4-10-fold by arsenite and HgCl₂, but was unchanged by AGNH, realgar and cinnabar. Thus, AGNH, realgar and cinnabar are much less toxic acutely than arsenite and HgCl₂. The chemical forms of As and Hg are extremely important factors in determining their disposition and toxicity.
authors.affiliation: Department of Pharmacology and Key Lab of Basic Pharmacology of Guizhou, Zunyi Medical College, Zunyi, China.
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.forename: Jun-Wen
authors.initials: JW
authors.lastname: Yan
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
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: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics; D001152:Arsenicals / Q000493:pharmacokinetics; D018053:Arsenites / Q000493:pharmacokinetics / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008516:Medicine, Chinese Traditional; D008627:Mercuric Chloride / Q000493:pharmacokinetics / Q000633:toxicity; D008628:Mercury / Q000493:pharmacokinetics; D017669:Mercury Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017670:Sodium Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D013440:Sulfides / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D001152:Arsenicals; D018053:Arsenites; D017669:Mercury Compounds; D012333:RNA, Messenger; D017670:Sodium Compounds; D013440:Sulfides; C017947:sodium arsenite; D008627:Mercuric Chloride; C058317:arsenic disulfide; D008668:Metallothionein; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008628:Mercury; D001151:Arsenic; C034211:cinnabar