Sorensen E M, Acosta D
J Toxicol Environ Health. 1985;16(3-4):425-40. doi: 10.1080/15287398509530752.
Primary cultures of intact, functional heptocytes were used to compare the relative toxicity of four nonsteroid antiinflammatory agents (NSAID)--benoxaprofen, orpanoxin, aspirin, and ibuprofen--with that of indomethacin. The relative toxicity of these compounds was evaluated on the basis of the release of lactate dehydrogenase, levels of urea (an indicator of a liver specific function), viability (based on dye exclusion), and morphology after a 12-h exposure to concentrations ranging from 0 to 1000 microM. Evaluation of the data obtained from these three parameters enabled us to rank these compounds from toxic to nontoxic, in decreasing order to toxicity: indomethacin greater than benoxaprofen greater than ibuprofen greater than or equal to aspirin greater than or equal to orpanoxin. Morphological evaluations of hepatocytes exposed to these agents under the same conditions supported the order of ranking for these compounds. Ultrastructurally, cells exposed to the two highest concentrations of indomethacin were severely damaged, as evidenced by marked cellular necrosis, nuclear pleomorphism, margination, swollen mitochondria, reductions in the number of microvilli, smooth endoplasmic reticulum proliferation, and cytoplasmic vacuolation. In comparison, exposure of hepatocytes to the highest dose of orpanoxin resulted only in increased vacuolation, a slight increase in cellular debris, and increased electron density of the cytoplasm of hepatocytes.
完整、有功能的肝细胞原代培养物被用于比较四种非甾体抗炎药（NSAID）——苯恶洛芬、奥帕诺辛、阿司匹林和布洛芬——与吲哚美辛的相对毒性。基于乳酸脱氢酶的释放、尿素水平（肝脏特定功能的指标）、活力（基于染料排斥法）以及在0至1000微摩尔浓度下暴露12小时后的形态学，对这些化合物的相对毒性进行了评估。对从这三个参数获得的数据进行评估，使我们能够将这些化合物按毒性从高到低排序：吲哚美辛＞苯恶洛芬＞布洛芬≥阿司匹林≥奥帕诺辛。在相同条件下对暴露于这些药物的肝细胞进行形态学评估，支持了这些化合物的排序顺序。在超微结构上，暴露于两种最高浓度吲哚美辛的细胞受到严重损伤，表现为明显的细胞坏死、核多形性、边缘化、线粒体肿胀、微绒毛数量减少、滑面内质网增殖以及细胞质空泡化。相比之下，肝细胞暴露于最高剂量的奥帕诺辛仅导致空泡化增加、细胞碎片略有增加以及肝细胞细胞质电子密度增加。
