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

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. 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. 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. MeHg was most toxic with LC50 of 4–20 μM, followed by NaAsO2 (LC50, 25–250 μM) and HgCl2 (LC50, 50–100 μM), Na2HAsO4(LC50, 60–400 μM), As2O3(LC50, 30–900 μM), and As2S2 (LC50, 100–500 μM). In comparison, the LC50 of realgar ranged from 250 to1500 μM; whereas cinnabar or HgS were approximately 20,000 μM and the toxicity of AGNH was in the range of 1500–8000 μM. Approximately 5000-fold differences exist between MeHg and HgS, and over 10-fold differences exist between NaAsO2 and As4S4. 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.