A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha‐Amanitin‐Induced Hepatotoxicity |
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Authors: | Aynur Sahin Mualla Aylin Arici Yeliz Yilmaz Sule Kalkan Nergiz Durmus Bekir Ugur Ergur Ilkay Yakut Aksu Ne?e Atabey Yesim Tuncok |
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Institution: | 1. Department of Emergency Medicine, Karadeniz Technical University School of Medicine, Trabzon, Turkey;2. Department of Medical Pharmacology, Dokuz Eylul University School of Medicine, Izmir, Turkey;3. Department of Medical Biology and Genetics, Dokuz Eylul University Institute of Health Sciences, Izmir, Turkey;4. Dokuz Eylul University Izmir Biomedicine and Genome Institute (iBG‐izmir), Izmir, Turkey;5. Division of Clinical Toxicology, Department of Medical Pharmacology, Dokuz Eylul University School of Medicine, Izmir, Turkey;6. Department of Histology and Embriology, Dokuz Eylul University School of Medicine, Izmir, Turkey;7. Department of Physiology, Dokuz Eylul University School of Medicine, Izmir, Turkey;8. Department of Medical Biology and Genetics, Dokuz Eylul University School of Medicine, Izmir, Turkey |
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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. |
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