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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms ofα-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.
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참고문헌 (27)
참고문헌 신청
Vetter J. / 1998 / Toxins of Amanita phalloides / Toxicon 36:13~24
Mas A. / 2005 / Mushrooms, amatoxins and the liver / Journal of hepatology 42:166~169
Bushnell DA / 2002 / Structural basis of transcription: α-amanitin-RNA polymerase II cocrystal at 2.8 Å resolution / Proceedings of the National Academy of Sciences 99:1218~1222
Nguyen VT / 1996 / In vivo degra-dation of RNA polymerase II largest subunit triggered by α-amanitin / Nucleic acids research 24:2924~2929
김보현 / 2017 / 알파 아마니틴에 의한 간독성에 대한 갯방풍의 보호 효과 / 대한임상독성학회지 15(2):107~115
Mas A. / 2005 / Mushrooms, amatoxins and the liver / Journal of hepatology 42:166~169
Bushnell DA / 2002 / Structural basis of transcription: α-amanitin-RNA polymerase II cocrystal at 2.8 Å resolution / Proceedings of the National Academy of Sciences 99:1218~1222
Nguyen VT / 1996 / In vivo degra-dation of RNA polymerase II largest subunit triggered by α-amanitin / Nucleic acids research 24:2924~2929
김보현 / 2017 / 알파 아마니틴에 의한 간독성에 대한 갯방풍의 보호 효과 / 대한임상독성학회지 15(2):107~115
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