SUPEROXIDE-DISMUTASE AND CATALASE PROTECT CULTURED-HEPATOCYTES FROM THE CYTO-TOXICITY OF ACETAMINOPHEN
SUPEROXIDE-DISMUTASE AND CATALASE PROTECT CULTURED-HEPATOCYTES FROM THE CYTO-TOXICITY OF ACETAMINOPHEN
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DOI：
10.1016/0006-291x(87)90491-8
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发表时间：
1987-12-31
影响因子：
3.1
通讯作者：
FARBER, JL
中科院分区：
文献类型：
--
作者：
KYLE, ME;MICCADEI, S;FARBER, JL
超氧化物歧化酶、过氧化氢酶和甘露醇在谷胱甘肽还原酶抑制剂BCNU存在下可防止对乙酰氨基酚对培养肝细胞的杀伤。在这些条件下，对乙酰氨基酚的细胞毒性取决于其代谢，因为β-萘甲酮是一种混合功能氧化抑制剂，可防止细胞杀伤。在用三价铁螯合剂去铁胺预防对乙酰氨基酚产生耐药性的肝细胞中，加入三价铁或二价铁可恢复对乙酰氨基酚的敏感性。在这种情况下，超氧化物歧化酶和过氧化氢酶在三价铁存在下防止对乙酰氨基酚的杀伤。相比之下，过氧化氢酶，而不是超氧化物歧化酶，防止细胞杀伤依赖于添加亚铁。这些结果证明了超氧阴离子和过氧化氢参与对乙酰氨基酚对培养的肝细胞的杀伤，并表明铁催化的Haber-Weiss反应产生的羟基自由基介导了细胞损伤。
Superoxide dismutase, catalase and mannitol prevent the killing of cultured hepatocytes by acetaminophen in the presence of an inhibitor of glutathione reductase, BCNU. Under these conditions, the cytotoxicity of acetaminophen depends upon its metabolism, since .beta.-naphthoflavone, an inhibitor of mixed function oxidation, prevents the cell killing. In hepatocytes made resistant to acetaminophen by pretreatent with the ferric iron chelator, deferoxamine, addition of ferric or ferrous iron restores the sensitivity to acetaminophen. In such a situation, both superoxide dismutase and catalase prevent the killing by acetaminophen in the presence of ferric iron. By contrast, catalase, but not superoxide dismutase, prevents the cell killing dependent upon addition of ferrous iron. These results document the participation of both superoxide anion and hydrogen peroxide in the killing of cultured hepatocytes by acetaminophen and suggest that hydroxyl radicals generated by an iron catalyzed Haber-Weiss reaction mediate the cell injury.