A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha-Amanitin-Induced Hepatotoxicity.

Abstract

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 hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α-AMA (α-AMA + SR) or 12 (α-AMA + 12R) or 24 (α-AMA + 24R) hr after α-AMA administration. Silibinin (5 mg/kg) (α-AMA + Sil) and normal saline (α-AMA + NS) were given simultaneously with α-AMA. We found that 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 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α-AMA in THLE-2 and THLE-3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α-AMA + NS. As a conclusion, resveratrol was found to be effective in α-AMA-induced hepatotoxicity with its anti-inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings.

• Authors: Aynur Sahin, Mualla Aylin Arici, Yeliz Yilmaz, Sule Kalkan, Nergiz Durmus, Bekir Ugur Ergur, Ilkay Yakut Aksu, Neşe Atabey, Yesim Tuncok
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 122 Issue 6 Pg. 633-642 (Jun 2018) ISSN: 1742-7843 [Electronic] England
• PMID: 29285878 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Chemical References

• Alpha-Amanitin
• Antioxidants
• Nucleic Acid Synthesis Inhibitors
• Protective Agents
• Silymarin
• Stilbenes
• Silybin
• Aspartate Aminotransferases
• Alanine Transaminase
• CASP3 protein, human
• Caspase 3
• Resveratrol

Topics

• Alanine Transaminase (blood)
• Alpha-Amanitin (antagonists & inhibitors, toxicity)
• Antioxidants (therapeutic use)
• Aspartate Aminotransferases (blood)
• Caspase 3 (metabolism)
• Cell Line
• Cell Survival (drug effects)
• Chemical and Drug Induced Liver Injury (pathology, prevention & control)
• Humans
• Liver (enzymology, pathology)
• Mushroom Poisoning (drug therapy)
• Nucleic Acid Synthesis Inhibitors (toxicity)
• Protective Agents (therapeutic use)
• Resveratrol
• Silybin
• Silymarin (therapeutic use)
• Stilbenes (therapeutic use)