Realgar- and cinnabar-containing An-Gong-Niu-Huang Wan (AGNH) is much less acutely toxic than sodium arsenite and mercuric chloride

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 6 g/kg. AGNH at 3 g/kg contains 2.8 mmol As/kg as realgar and 1.18 mmol 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 8 h 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.