Karahan, SelimAtlı, ZehraKaya, ErtuğrulÖzdemir, FerideBoğa, Mehmetİzgi, Sevcan2024-08-232024-08-2320222548-0731https://search.trdizin.gov.tr/tr/yayin/detay/1168019https://hdl.handle.net/20.500.12684/15228Background and Aims: Amanita phalloides is the deadliest toxic mushroom in the world and causes death from acute liver failure. ?-amanitin (?-AMA), the most potent toxin, inhibits RNA polymerase II in hepatocytes, stops protein synthesis, and causes hepatotoxicity. However, the information about the mechanisms underlying hepatotoxicity caused by ?-AMA is quite inadequate. This study aims to reveal the complex necrotic and apoptotic mechanisms occurring in mouse hepatocytes de- pending on A. phalloides exposure time in vivo. Methods: BALB-c male mice were divided into 5 groups (n=7): control, ?-AMA-2, ?-AMA-12, ?-AMA-72, and ?-AMA-96 groups. A poisoning model was created by oral administration of A. phalloides mushroom extract containing 10 mg/kg of ?-AMA to mice and they were sacrificed after 2, 12, 72, and 96 h. Then, TNF-?, Bax, caspase-3, and Bcl-2 gene expression levels in liver tissues were examined by the RT-qPCR method. Time-dependent damage to liver tissues was also evaluated histopathologically. Results: RT-qPCR results showed that proinflammatory cytokine TNF-? mRNA expression levels increased in mouse liver tissues at 2 and 12 h after A. phalloides administration compared among the groups. Bax mRNA expression levels increased in the 12 and 72 h after A. phalloides ingestion. It was observed that caspase-3 mRNA expression levels increased in the 72 and 96 h groups compared among the groups, while Bcl-2 mRNA expression levels decreased in the 72 and 96 h groups. Conclusion: Our findings showed that necrotic mechanisms develop in the early period after A. phalloides mushroom poison- ing, and then apoptotic mechanisms are effective. In conclusion, understanding the mechanisms of A. phalloides-induced hepatotoxicity will provide important information for new treatment strategies to be developed.en10.26650/IstanbulJPharm.2022.1136288info:eu-repo/semantics/openAccessArticle3522812881168019