Higaki J, Harada H, Tonda K, Hirata M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Pharmacol Toxicol. 1989 Jul;65(1):21-4. doi: 10.1111/j.1600-0773.1989.tb01120.x.
The effects of several diuretics, including tienilic acid and indacrinone, on isolated rat heaptocytes were examined. Addition of tienilic acid and indacrinone at 1 mM to a suspension of freshly isolated cells caused dose-dependent loss of cell viability as judged by the LDH-latency test. Survey of 19 structurally related compounds revealed that the extent of cell injury and chemical structure were correlated, and an intense adverse effect was attributed to the 2-thienylcarbonyl moiety. Several other factors influencing cell viability are also disclosed. Further study revealed that tienilic acid and indacrinone were toxic to the primary culture of hepatocytes at a lower dose than that a freshly isolated hepatocytes. Thus, an isolated hepatocyte system can be used to select compounds displaying low hepatotoxicity, as for example is needed when screening diuretics.
研究了包括替尼酸和茚达立酮在内的几种利尿剂对离体大鼠肝细胞的影响。通过乳酸脱氢酶（LDH）潜伏期试验判断，向新鲜分离细胞的悬浮液中添加1 mM的替尼酸和茚达立酮会导致细胞活力呈剂量依赖性丧失。对19种结构相关化合物的研究表明，细胞损伤程度与化学结构相关，强烈的不良反应归因于2-噻吩羰基部分。还揭示了其他几个影响细胞活力的因素。进一步研究表明，替尼酸和茚达立酮对原代培养肝细胞的毒性剂量低于对新鲜分离肝细胞的毒性剂量。因此，离体肝细胞系统可用于筛选低肝毒性的化合物，例如在筛选利尿剂时就需要这样做。
