Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells

The effects of triterpene compounds on cadmium toxicity were investigated in HepG2 cells. Ten triterpene compounds were examined, namely, betulin, soyasapogenol A, soyasapogenol B, ursolic acid, uvaol, oleanolic acid, friedelin, glycyrrhizin, 18 alpha-glycyrrhetinic acid, and 18 beta-glycyrrhetinic acid, and betulin, soyasapogenol A, and uvaol were found to reduce the toxicity of CdCl2. In particular, betulin almost completely abolished the cytotoxicity of CdCl2 at concentrations as low as 0.1 mg/ml. The effects of betulin were particularly apparent when added to the culture medium before the addition of CdCl2. Moreover, when HepG2 cells were incubated with betulin and then incubated in fresh betulin-free medium before the addition of CdCl2, the toxic effects of cadmium were reduced. Betulin had no significant effect on the intracellular accumulation of cadmium, nor did it bind to cadmium, at least not in a test tube. When HepG2 cells were treated first with cycloheximide or actinomycin D, the subsequent protective effect of betulin against cadmium toxicity was significantly reduced, suggesting that betulin might protect cells against cadmium toxicity by inducing the synthesis of a certain protein or proteins. The synthesis of metallothionein, a protein that is known to reduce the toxicity of heavy metals, was not induced by betulin. However, using the differential display method, we confirmed that betulin promoted the expression of several genes. Our findings suggest that betulin might reduce cadmium toxicity by promoting the synthesis of certain proteins that protect cells against the toxic effects of cadmium.