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人肝细胞和大鼠肝细胞原代培养物对黄曲霉毒素B1诱导的细胞毒性的差异反应以及肝保护剂(+)-氰定醇-3的保护作用

Differential response of primary cultures of human and rat hepatocytes to aflatoxin B1-induced cytotoxicity and protection by the hepatoprotective agent (+)-cyanidanol-3.

作者信息

Bégué J M, Baffet G, Campion J P, Guillouzo A

机构信息

Unité de Recherches Hépatologiques U 49, INSERM, Hôpital de Pontchaillou, Rennes, France.

出版信息

Biol Cell. 1988;63(3):327-33. doi: 10.1111/j.1768-322x.1988.tb00756.x.

DOI:10.1111/j.1768-322x.1988.tb00756.x
PMID:3147113
Abstract

The acute hepatotoxicity induced by aflatoxin B1 (AFB1) and the potential protective effect of (+)-cyanidanol-3 (Catergen) were evaluated in both human and rat hepatocytes in primary cultures. AFB1-induced acute toxicity was visualized by light microscope observation and quantified by measurement of lactic dehydrogenase activity in the medium. Human hepatocytes were susceptible to AFB1-induced cytotoxicity but no evident relationship between the concentration of mycotoxin and the extent of cellular damage was established. (+)-Cyanidanol-3 was not toxic at concentrations up to 2 x 10(-3)M, but no obvious protective effect from AFB1-induced injury was evidenced in human cells. By contrast, rat hepatocytes responded in a dose-related manner to AFB1. (+)-Cyanidanol was toxic at 10(-3)M, but even at this concentration exerted a strong protective effect against AFB1-induced cytotoxicity. Such species differences suggest the existence of metabolic differences in both AFB1 and (+)-cyanidanol-3 activating and deactivating mechanisms.

摘要

在原代培养的人和大鼠肝细胞中评估了黄曲霉毒素B1(AFB1)诱导的急性肝毒性以及(+)-氰定醇-3(Catergen)的潜在保护作用。通过光学显微镜观察可视化AFB1诱导的急性毒性,并通过测量培养基中的乳酸脱氢酶活性进行定量。人肝细胞对AFB1诱导的细胞毒性敏感,但未确定霉菌毒素浓度与细胞损伤程度之间的明显关系。(+)-氰定醇-3在浓度高达2×10⁻³M时无毒,但在人细胞中未证明对AFB1诱导的损伤有明显保护作用。相比之下,大鼠肝细胞对AFB1呈剂量相关反应。(+)-氰定醇在10⁻³M时有毒,但即使在此浓度下也对AFB1诱导的细胞毒性发挥了强大的保护作用。这种物种差异表明在AFB1和(+)-氰定醇-3的激活和失活机制中存在代谢差异。

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Differential response of primary cultures of human and rat hepatocytes to aflatoxin B1-induced cytotoxicity and protection by the hepatoprotective agent (+)-cyanidanol-3.人肝细胞和大鼠肝细胞原代培养物对黄曲霉毒素B1诱导的细胞毒性的差异反应以及肝保护剂(+)-氰定醇-3的保护作用
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In Vitro Cell Dev Biol. 1990 Jan;26(1):67-74. doi: 10.1007/BF02624157.