Gene expression profiles for apoptotic and necrotic pathways during Amanita phalloides intoxication in mice
Küçük Resim Yok
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Istanbul Univ, Fac Pharmacy
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background and Aims: Amanita phalloides is the deadliest toxic mushroom in the world and causes death from acute liver failure. alpha-amanitin (alpha-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 alpha-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, alpha-AMA-2, alpha-AMA-12, alpha-AMA-72, and alpha-AMA-96 groups. A poisoning model was created by oral administration of A. phalloides mushroom extract containing 10 mg/kg of alpha-AMA to mice and they were sacrificed after 2, 12, 72, and 96 h. Then, TNF-alpha, 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-alpha mRNA expression levels increased in mouse liver tissues at 2 and 12 h afterA. phalloides administration compared among the groups. BaxmRNA expression levels increased in the 12 and 72 h afterA. 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 afterA. 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.
Açıklama
Anahtar Kelimeler
?-amanitin, TNF-?, Bax, caspase-3, Bcl-2, RT-qPCR, Alpha-Amanitin, Amatoxins, Mushroom, Diagnosis, Lethal
Kaynak
Istanbul Journal of Pharmacy
WoS Q Değeri
N/A
Scopus Q Değeri
Cilt
52
Sayı
3
