Comparative Study On Acute Toxicity Of Niu-Huang-Jie-Du Tablets (NHJDT), Realgar And Other Inorganic Arsenic Compounds

Objective:To compare acute toxicity of Niu-Huang-Jie-Du Tablets (NHJDT), realgar with arsenicals in mice and cultured cells.Methods:Adult KunMing mice were randomly divided into 9 groups and were given a single intragastric administration of NHJDT (60,180 and 600 mg/kg), JingZhi NHJDT (600 mg/kg),600 mg/kg of realgar and arsenic disulfide (As2S2),42 mg/kg of sodium arsenite (NaAsO2) and 100 mg/kg of sodium arsenate (Na2HAsO4). Eight hours after administration, blood biochemistry, histopathology, tissue As contents, metal toxicity biomarker Metallothionein-1 (MT-1) mRNA were determined, respectively. Cultured FaDu cells were exposed to arsenicals, and cells were collected at 30,60, and 120 min for cellular As accumulation by AFS, and LC50 were determined after 48 h by the MTS assay.Results:Accumulation of As in liver and kidneys of arsenite and arsenate-treated animals were significantly higher than NHJDT, realgar and As2S2 groups, accompanied by the higher levels of serum (ALT, AST, UREA, CREA), indicative of liver and kidney injuries. Histology showed more pathological injuries of liver and kidney in NaAsO2 and Na2HAsO4 groups, along with elevated MT-1 mRNA gene expression, but not in other groups. Similarly, the FaDu cells cytotoxicity and cellular As accumulation in NaAsO2 and Na2HAs04 groups were also far higher than the other groups.Conclusions:NHJDT and realgar are much less acute toxic than arsenite and arenate. The use of total As to evaluate the safety of realgar-containing NHJDT is inappropriate.