Smith P F, Fisher R, Shubat P J, Gandolfi A J, Krumdieck C L, Brendel K
Toxicol Appl Pharmacol. 1987 Mar 15;87(3):509-22. doi: 10.1016/0041-008x(87)90257-2.
Two well-known hepatotoxicants, allyl alcohol (AA) and bromobenzene (BB), were studied using an in vitro system of cultured liver slices from control and phenobarbital-treated rats, respectively. Dose- and time-dependent increases in media lactate dehydrogenase (LDH), and decreases in slice K+ content and in protein synthesis were observed in rat liver slices incubated with either compound at concentrations between 0.1 and 1 mM over a period of 6 hr. The histopathological changes which occurred in the intoxicated slices appeared to parallel these biochemical changes. Additionally, the toxicity of either BB or AA, evaluated at 4 hr, was inhibited when slices were preincubated for 30 min with beta-ethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) (0.1 mM) or pyrazole (1.0 mM), respectively. In this in vitro incubation system the cytotoxicity of xenobiotics can be studied under conditions where the multicellular hepatic lobular architecture is partially maintained, and alterations in biochemical and functional processes may be correlated to pathological changes.
分别使用来自对照大鼠和苯巴比妥处理大鼠的培养肝切片体外系统，对两种著名的肝毒性物质烯丙醇（AA）和溴苯（BB）进行了研究。在0.1至1 mM浓度下，将两种化合物与大鼠肝切片孵育6小时，观察到培养基乳酸脱氢酶（LDH）呈剂量和时间依赖性增加，切片钾离子（K+）含量和蛋白质合成减少。中毒切片中出现的组织病理学变化似乎与这些生化变化平行。此外，当切片分别与盐酸β-乙基-2,2-二苯基戊酸酯（SKF 525-A）（0.1 mM）或吡唑（1.0 mM）预孵育30分钟时，在4小时评估的BB或AA的毒性受到抑制。在这个体外孵育系统中，可以在部分维持多细胞肝小叶结构的条件下研究外源性物质的细胞毒性，并且生化和功能过程的改变可能与病理变化相关。
