A comparison of the effectiveness of silibinin and resveratrol in preventing alpha-amanitin-induced hepatotoxicity

Objective: Amanita phalloides species mushrooms containing alpha amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in liver toxicity and acute hepatic failure. Existing antidotes, such as silibinin and penicillin G, are not sufficiently effective in the prevention and/or resolution of α-AMA induced liver toxicity. We investigated the effects of resveratrol on α-AMA induced liver toxicity and compared with silibinin, a known antidote in the in vivo toxicity model. Method: The in vivo toxicity model was established with 1.4 mg/kg α-AMA, which results in significant elevation in AST and ALT values in Balb/c mice and also causes histomorphological damage in the liver. α-AMA+0.9% sodium chloride (NaCl) was administered in the control group, and -AMA+dimethyl sulfoxide (DMSO) in the DMSO group, while 30 mg/kg resveratrol was administered in the resveratrol groups, in three different treatment protocols, simultaneously with α-AMA (α-AMA +ER), after 12 h (α-AMA +12R) and after 24 h (α-AMA +24R). Silibinin at 5 mg/kg (α-AMA +Sil) was administered at 6-h intervals simultaneously with α-AMA. Mice were sacrificed at the end of the 48-h experimental protocol. AST, ALT, total bilirubin, and direct bilirubin levels were investigated from serum specimens collected, while antioxidant enzymes and histomorphological examinations were performed from liver tissue. TUNEL and active caspase-3 were examined and apoptosis was evaluated. Results: The liver transaminase levels in α-AMA+SR and α-AMA+12R groups and histomorphologic injury score in the α-AMA+SR, α-AMA+12R, α-AMA+24R and α-AMA+Sil groups were significantly lower than that of the α-AMA+NS group. Resveratrol, decreased mononuclear cell infiltration, necrosis and active caspase-3 immunopsitivity in liver. Conclusion: Resveratrol was found to be effective in α-AMA induced liver toxicity with its anti-inflamatory properties. It is a promising antidote with the potential for use in the treatment of liver toxicity associated with Amanita phalloides type mushroom poisonings.