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由肝毒素烯丙醇和溴苯在未成熟和成年Fischer 344大鼠中所确定的功能性肝细胞异质性。

Functional hepatocellular heterogeneity determined by the hepatotoxins allyl alcohol and bromobenzene in immature and adult Fischer 344 rats.

作者信息

Klinger W, Devereux T, Maronpot R, Fouts J

出版信息

Toxicol Appl Pharmacol. 1986 Mar 30;83(1):108-14. doi: 10.1016/0041-008x(86)90328-5.

DOI:10.1016/0041-008x(86)90328-5
PMID:3006282
Abstract

Adult (male, 75-90 days old) and immature rats (both sexes, 11-12 days old) were treated with allyl alcohol or bromobenzene to induce periportal or centrilobular hepatic injury, respectively. Histologically confirmed liver lesions were produced in adult rats with both treatments. In adult rats, allyl alcohol decreased hepatic cytochrome P-450, benzphetamine N-demethylation, and ethoxyresorufin O-deethylation activities all by about 30%, whereas bromobenzene influenced these parameters differently: cytochrome P-450 was lowered by 55%, benzphetamine N-demethylation by 80%, and ethoxyresorufin O-deethylation by 90%. Cytochrome c reductase, 5'-nucleotidase, glucose-6-phosphatase, and glutamate-pyruvate transaminase activities were not significantly influenced. In immature rats, allyl alcohol did not produce histopathological alterations in liver, but did lower both cytochrome P-450 concentration (30%) and ethoxyresorufin O-deethylation (75%). Benzphetamine N-demethylation was not significantly affected. Bromobenzene produced typical centrilobular liver damage and a decrease of both cytochrome P-450 (20%) and ethoxyresorufin O-deethylation (50%). Benzphetamine N-demethylation was increased slightly, but not significantly. The differences in effects of the two hepatotoxins in adult vs immature rats seem to indicate that the hepatocellular heterogeneity of xenobiotic metabolism which is seen in adult liver (perivenous vs periportal areas) is not well developed in the immature animal.

摘要

成年大鼠(雄性,75 - 90日龄)和未成年大鼠(雌雄均有,11 - 12日龄)分别用烯丙醇或溴苯处理,以分别诱导门周或小叶中心性肝损伤。两种处理均在成年大鼠中产生了组织学证实的肝脏病变。在成年大鼠中,烯丙醇使肝细胞色素P - 450、苄非他明N - 去甲基化和乙氧异唑磷O - 去乙基化活性均降低约30%,而溴苯对这些参数的影响不同:细胞色素P - 450降低55%,苄非他明N - 去甲基化降低80%,乙氧异唑磷O - 去乙基化降低90%。细胞色素c还原酶、5'-核苷酸酶、葡萄糖-6-磷酸酶和谷丙转氨酶活性未受到显著影响。在未成年大鼠中,烯丙醇未在肝脏产生组织病理学改变,但降低了细胞色素P - 450浓度(30%)和乙氧异唑磷O - 去乙基化(75%)。苄非他明N - 去甲基化未受到显著影响。溴苯产生了典型的小叶中心性肝损伤,细胞色素P - 450(20%)和乙氧异唑磷O - 去乙基化(50%)均降低。苄非他明N - 去甲基化略有增加,但不显著。两种肝毒素在成年大鼠和未成年大鼠中作用的差异似乎表明,成年肝脏中所见的异生物质代谢的肝细胞异质性(肝静脉周围与门周区域)在未成年动物中发育不完善。

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引用本文的文献

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Increased turnover of intrahepatic bile ducts induced by bromobenzene.溴苯诱导的肝内胆管周转率增加。
Dig Dis Sci. 1995 Apr;40(4):730-3. doi: 10.1007/BF02064969.
2
Methods for the study of liver cell heterogeneity.肝细胞异质性的研究方法。
Histochem J. 1989 Sep-Oct;21(9-10):517-29. doi: 10.1007/BF01753352.