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- Title
A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha‐Amanitin‐Induced Hepatotoxicity.
- Authors
Sahin, Aynur; Arici, Mualla Aylin; Yilmaz, Yeliz; Kalkan, Sule; Durmus, Nergiz; Ergur, Bekir Ugur; Yakut Aksu, Ilkay; Atabey, Neşe; Tuncok, Yesim
- Abstract
Abstract: <italic>Amanita phalloides</italic> 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 <italic>in vivo</italic> and <italic>in vitro</italic> toxicity models. In the <italic>in vivo</italic> 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 <italic>in vitro</italic> 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 <italic>in vivo</italic> conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with <italic>Amanita phalloides</italic> type mushroom poisonings.
- Subjects
AMANITA; MUSHROOMS; HEPATOTOXICOLOGY; ANTIDOTES; SILIBININ
- Publication
Basic & Clinical Pharmacology & Toxicology, 2018, Vol 122, Issue 6, p633
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/bcpt.12954