Gene expression profiles for apoptotic and necrotic pathways during Amanita phalloides intoxication in mice

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dc.contributor.authorKarahan, Selim
dc.contributor.authorAtli, Zehra
dc.contributor.authorKaya, Ertugrul
dc.contributor.authorOzdemir, Feride
dc.contributor.authorBoga, Mehmet
dc.contributor.authorIzgi, Sevcan
dc.date.accessioned2024-04-24T17:20:22Z
dc.date.available2024-04-24T17:20:22Z
dc.date.issued2022
dc.departmentDicle Üniversitesien_US
dc.description.abstractBackground 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.en_US
dc.description.sponsorshipSci-entific Research Projects Coordinator of Dicle University [DUBAP:DUSAM.21.002]en_US
dc.description.sponsorshipAcknowledgement: The authors are thankful to the Sci-entific Research Projects Coordinator of Dicle University (DUBAP:DUSAM.21.002) for providing financial support.en_US
dc.identifier.doi10.26650/IstanbulJPharm.2022.1136288
dc.identifier.endpage288en_US
dc.identifier.issn2587-2087
dc.identifier.issue3en_US
dc.identifier.startpage281en_US
dc.identifier.trdizinid1168019
dc.identifier.urihttps://doi.org/10.26650/IstanbulJPharm.2022.1136288
dc.identifier.urihttps://search.trdizin.gov.tr/yayin/detay/1168019
dc.identifier.urihttps://hdl.handle.net/11468/18995
dc.identifier.volume52en_US
dc.identifier.wosWOS:000954321500005
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakTR-Dizin
dc.language.isoenen_US
dc.publisherIstanbul Univ, Fac Pharmacyen_US
dc.relation.ispartofIstanbul Journal of Pharmacy
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subject?-Amanitinen_US
dc.subjectTnf-?en_US
dc.subjectBaxen_US
dc.subjectCaspase-3en_US
dc.subjectBcl-2en_US
dc.subjectRt-Qpcren_US
dc.titleGene expression profiles for apoptotic and necrotic pathways during Amanita phalloides intoxication in miceen_US
dc.titleGene expression profiles for apoptotic and necrotic pathways during Amanita phalloides intoxication in mice
dc.typeArticleen_US

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