Klingensmith J S, Lockard V, Mehendale H M
Exp Mol Pathol. 1983 Aug;39(1):1-10. doi: 10.1016/0014-4800(83)90036-9.
In a subchronic dietary pretreatment protocol chlordecone (CD) is a powerful potentiator of CCl4 hepatotoxicity, as indicated by biochemical, hepatofunctional, histopathological, and lethality parameters. The purpose of this investigation is to further explore the CD + CCl4 interaction in an acute CD pretreatment protocol and to compare the two pretreatment protocols in terms of their effect upon quantitative histopathology, serum enzymes, and lethality. Groups of four male rats received one of the following four pretreatments: chlordecone (10 mg/kg; single po), mirex (10 mg/kg; single po), phenobarbital (PB) (80 mg/kg/day for 2 successive days; ip in 0.9% saline), or corn oil vehicle (1 ml/kg; single po). Twenty-four hours later, the rats were given a single ip injection of CCl4 (0.1 ml/kg). Twenty-four hours after CCl4 administration, serum enzymes (SGPT, SGOT, and ICD) were measured and the livers removed and fixed in 10% buffered formalin for histological evaluation. The LD50 were determined by the method of moving averages. CD + CCl4 was the most hepatotoxic combination, in terms of serum enzyme elevations and lethality followed by PB + CCl4. The PB + CCl4 combination caused a greater degree of hepatocyte necrosis. These findings indicate that the acute pretreatment with CD enhances hepatotoxicity and the lethality of CCl4 in a fashion qualitatively similar to the subchronic pretreatment protocol.
在亚慢性饮食预处理方案中，开蓬（CD）是四氯化碳肝毒性的强力增效剂，生化、肝功能、组织病理学和致死率参数均表明了这一点。本研究的目的是在急性CD预处理方案中进一步探究CD + 四氯化碳的相互作用，并比较这两种预处理方案在定量组织病理学、血清酶和致死率方面的影响。将四只雄性大鼠分为一组，分别接受以下四种预处理之一：开蓬（10毫克/千克；单次口服）、灭蚁灵（10毫克/千克；单次口服）、苯巴比妥（PB）（80毫克/千克/天，连续两天；腹腔注射于0.9%生理盐水中）或玉米油载体（1毫升/千克；单次口服）。24小时后，给大鼠单次腹腔注射四氯化碳（0.1毫升/千克）。在给予四氯化碳24小时后，测量血清酶（谷丙转氨酶、谷草转氨酶和异柠檬酸脱氢酶），取出肝脏并固定于10%缓冲甲醛中进行组织学评估。半数致死剂量通过移动平均法测定。就血清酶升高和致死率而言，CD + 四氯化碳是肝毒性最强的组合，其次是PB + 四氯化碳。PB + 四氯化碳组合导致肝细胞坏死的程度更大。这些发现表明，急性CD预处理增强了四氯化碳的肝毒性和致死率，其方式在质量上与亚慢性预处理方案相似。
