Chemical form of metals in traditional medicines underlines potential toxicity in cell cultures

Ethnopharmacological relevance: Mercury (Hg) and arsenic (As) are frequently found in traditional medicines as sulfides, such as cinnabar (HgS) and realgar (As4S4). There is a general perception that any medicinal use of such metal-containing remedies is unacceptable. An opposing opinion is that different chemical forms of arsenic and mercury have different toxic potentials. Aim of the study: To clarify this question, cinnabar, realgar, and cinnabar- and realgar-containing traditional medicine An-Gong-Niu-HuangWan (AGNH), were compared to well-known mercurials (HgS, HgCl2 and MeHg) and arsenicals (As2S2, As2O3, NaAsO2, and Na2HAsO4) for their cytotoxicity in human and rodent cell lines. Materials and method: Cultured cells derived from target organs such as brain (HAPI) and liver (Hep3B, HepG2 and TRL1215) were treated with chemicals for 48 h and cytotoxicity was determined by the MTS assay. Results: MeHg was most toxic with LC50 of 4-20 mu M, followed by NaAsO2 (LC50, 25-250 mu M) and HgCl2 (LC50, 50-100 mu M), Na2HAsO4(LC50, 60-400 mu M), As2O3(LC50, 30-900 mu M), and As2S2 (LC50, 100-500 mu M). In comparison, the LC50 of realgar ranged from 250 to 1500 mu M; whereas cinnabar or HgS were approximately 20,000 mu M and the toxicity of AGNH was in the range of 1500-8000 mu M. Approximately 5000-fold differences exist between MeHg and HgS, and over 10-fold differences exist between NaAsO2 and As4S4. Conclusions: Chemical forms of metals are important factor in determining their toxicity in traditional medicines, both cinnabar and realgar are much less toxic than well-known mercurial and arsenicals. (C) 2011 Elsevier Ireland Ltd. All rights reserved.