Lupo S, Hewitt W R, Rush G F
Toxicol Lett. 1986 Nov;34(1):5-11. doi: 10.1016/0378-4274(86)90139-6.
Isolated perfused livers from male and female Sprague-Dawley rats were exposed to cadmium chloride (50 and 200 microM). Acute hepatotoxicity was investigated by measuring cadmium-induced changes in bile flow, urea synthesis and alanine aminotransferase (ALT) leakage. Cadmium-induced lipid peroxidation was estimated by formation of conjugated dieners and thiobarbituric acid (TBA) reactants. Cadmium, at both concentrations, caused a rapid decrease in bile flow (within 40 min) and complete cholestasis within 70 min exposure in livers perfused from both male and female rats. Cadmium exposure (50 and 200 microM) also resulted in the leakage of ALT into the perfusate within 60 min. In contrast, exposure of isolated rat hepatocytes to as high as 500 microM cadmium did not result in enzyme leakage until 180 min exposure. Sex differences in cadmium-induced cholestasis and ALT leakage were not observed at these concentrations. Malondialdehyde was not detected in the perfusate nor were conjugated dienes detected in liver tissue following 90 min cadmium exposure. These data demonstrate that the isolated perfused rat liver (IPRL) is a sensitive system in which to study chemically induced hepatotoxicity. Cadmium rapidly causes functional alterations and cellular damage in perfused livers from both male and female rats. Cadmium-induced liver injury was apparently not related to lipid peroxidation.
将雄性和雌性斯普拉格-道利大鼠的离体灌注肝脏暴露于氯化镉（50和200微摩尔）。通过测量镉诱导的胆汁流量、尿素合成和丙氨酸转氨酶（ALT）泄漏的变化来研究急性肝毒性。通过共轭二烯和硫代巴比妥酸（TBA）反应物的形成来估计镉诱导的脂质过氧化。在两种浓度下，镉都会导致胆汁流量迅速下降（40分钟内），并且在雄性和雌性大鼠灌注的肝脏中，暴露70分钟内会出现完全胆汁淤积。镉暴露（50和200微摩尔）还会导致ALT在60分钟内泄漏到灌注液中。相比之下，离体大鼠肝细胞暴露于高达500微摩尔的镉中，直到暴露180分钟才会导致酶泄漏。在这些浓度下未观察到镉诱导的胆汁淤积和ALT泄漏的性别差异。镉暴露90分钟后，在灌注液中未检测到丙二醛，在肝脏组织中也未检测到共轭二烯。这些数据表明，离体灌注大鼠肝脏（IPRL）是研究化学诱导肝毒性的敏感系统。镉会迅速导致雄性和雌性大鼠灌注肝脏的功能改变和细胞损伤。镉诱导的肝损伤显然与脂质过氧化无关。
