Erdosteine reduces cytotoxicity induced by alpha- and beta-amanitin, but not gamma-amanitin, in CA3 hepatocyte cultures

Amanitin poisoning still has no particular, effective antidote. Erdosteine has been shown to protect numerous tissues, particularly those in the liver. This study investigates the potential therapeutic effects of erdosteine on alpha-, beta- and gamma-amanitin-induced hepatotoxicity in in vitro models. Three hours after administering amatoxins at various concentrations (1–50 μg/mL) to the cells of the C3A human hepatocyte cell line, erdosteine was administered in different concentrations (i.e., 1, 10, 50, 100 and 250 μg/mL). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was selected to determine cell viability. When concentrations of 1, 10, 50, 100 and 250 μg/mL of erdosteine were applied to cell lines, the following cell viability rates were obtained: 106%,99%,93%,86% and 86%, respectively, at a 10 μg/mL alpha-amanitin-induced toxicity; 43%,41%,41%,37% and 35%, respectively, at a 25 μg/mL alpha-amanitin-induced toxicity; 44%,42%,41%,39% and 41%, respectively, at a 50 μg/mL alpha-amanitin-induced toxicity; 136%,142%,143%,137% and 120%, respectively, at a 10 μg/mL beta-amanitin-induced toxicity; 113%,107%,107%,106% and 86%, respectively, at a 25 μg/mL beta-amanitin-induced toxicity; 78%,77%,77%,74% and 70%, respectively, at a 10 μg/mL gamma-amanitin-induced toxicity; and 39%,40%,39%,35% and 31%, respectively, at a 25 μg/mL gamma-amanitin-induced toxicity. This study was the first to evaluate the in vitro efficacy of erdosteine in cytotoxicity induced by alpha-, beta- and gamma-amanitin. Non-high (low and medium) doses of erdosteine are capable of nearly entirely preventing toxicity at mild hepatotoxic concentrations caused by amatoxin and partially preventing toxicity at moderate and severe concentrations. The beneficial effects of erdosteine, especially on the toxicity of alpha- and beta-amanitin, are promising.