文章基本信息

标题：Potentiation of Acetaminophen Hepatotoxicity by Doxapram in Mouse Primary Cultured Hepatocytes
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作者：Shuuichi KANNO ; Masaaki ISHIKAWA ; Motoaki TAKAYANAGI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2000
卷号：23
期号：4
页码：446-450
DOI：10.1248/bpb.23.446
出版社：The Pharmaceutical Society of Japan
摘要：The augmentation by doxapram (DOP) of the reduction in viability and of the apoptosis of cells induced by acetaminophen (AA) was examined in mouse primary cultured hepatocytes. Loss of viability on exposure to AA and/or DOP in cultured hepatocytes was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and the apoptosis of cultured hepatocytes was detected by nuclear morphologic observation and from a ladder-like DNA fragmentation pattern. The combination of AA (5 mM) and DOP (10, 20, 50 or 100 μM) potentiated the reduction in cell viability and increased the oxidative stress. Hepatocytes exposed for 24 h to AA (5 mM) plus DOP (100 μM), showed atrophy of nuclei, including chromatin condensation and a ladder-like DNA fragmentation pattern, characteristic of apoptosis. Benzyl-oxycarbonyl-Asp-CH₂OC (O)-2, 6-dichlorobenzene (Z-Asp-CH₂-DCB, 50 μM), an inhibitor for caspases, improved the viability and ladder-like DNA fragmentation in cells exposed to DOP (200 or 500 μM) alone or AA (5 mM) plus DOP (100 μM). However, loss of viability on exposuer to a high concentration of AA (10 mM) and ladder-like DNA fragmentation were not affected by Z-Asp-CH₂-DCB. These results indicated that the synergistic increase in oxidative stress, activation of caspases and DNA fragmentation induced by DOP potentiated the hepatotoxicity of AA.
关键词：doxapram;acetaminophen;mouse primary cultured hepatocyte;apoptosis;caspase