Grant Roberta L
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas, Austin, TX 78712, United States of America.
Toxicol In Vitro. 2020 Apr;64:104634. doi: 10.1016/j.tiv.2019.104634. Epub 2019 Oct 15.
In vivo and in vitro animal models are used to investigate the toxicological modes of action of a substance as surrogates for humans since it is not ethical to conduct certain experiments in humans. The toxic actions of many compounds are manifested in specific organs, known as target organs of toxicity. Thus, in vitro systems that use cells derived from that target organ are best used to understand toxicological mechanisms. This article reviews the development of primary cultures of rabbit corneal epithelial cells which retain tissue specific and functional properties of in vivo cells as an experimental in vitro model to study ocular toxicity. This model system was used to evaluate initial ocular toxicity and mode of action of cocaine, tetracaine, and proparacaine, widely used local anesthetics. Initial toxicity and toxicity rankings of eight surfactants were determined using four different cytotoxicity endpoints. In addition, modes of action of delayed and prolonged cell injury after CE cells were treated with benzalkonium chloride, a cationic surfactant, and sodium dodecyl sulfate, an anionic surfactant, were investigated at multiple postexposure times after a 1-h treatment. The two surfactants produced distinctly different prolonged effects on cultured corneal epithelial cells, which may suggest these surfactants differentially affect cellular recovery.
体内和体外动物模型被用作研究物质毒理学作用模式的替代物，以替代人体实验，因为在人体上进行某些实验不符合伦理道德。许多化合物的毒性作用表现在特定器官，即所谓的毒性靶器官。因此，使用源自该靶器官的细胞的体外系统最适合用于了解毒理学机制。本文综述了兔角膜上皮细胞原代培养物的发展，这些细胞保留了体内细胞的组织特异性和功能特性，作为研究眼毒性的体外实验模型。该模型系统用于评估可卡因、丁卡因和丙美卡因这三种广泛使用的局部麻醉剂的初始眼毒性和作用模式。使用四种不同的细胞毒性终点来确定八种表面活性剂的初始毒性和毒性排名。此外，在用阳离子表面活性剂苯扎氯铵和阴离子表面活性剂十二烷基硫酸钠处理角膜上皮细胞1小时后，在多个暴露后时间点研究了延迟和延长的细胞损伤作用模式。这两种表面活性剂对培养的角膜上皮细胞产生了明显不同的延长作用，这可能表明这些表面活性剂对细胞恢复的影响不同。
