Perrissoud D, Testa B
Arzneimittelforschung. 1986 Aug;36(8):1249-53.
Carbon tetrachloride (CCl4) added to isolated rat hepatocytes produces toxic effects which were assessed by monitoring the release of aspartate aminotransferase (ASAT). CBrCl3 was equitoxic with CCl4, while CHCl3 was inactive, suggesting solvent properties not to be involved. The CCl4-mediated toxicity was markedly decreased by carbon monoxide, indicating possible activation by cytochrome P 450. 55 flavonoid compounds were tested for their ability to interfere with CCl4-induced release of ASAT. The compounds are cianidanol, 3-ethers and 3-esters thereof, flavanones, flavanolols, flavones and flavanols. The more hydrophilic compounds inhibit the CCl4-induced toxicity, while the lipophilic derivatives are potentiators. No other structure-activity relationships are apparent. The results are discussed in terms of the mechanisms of action of the compounds and of the validity of the technique as a screening test for hepatotropic agents.
将四氯化碳（CCl4）添加到分离出的大鼠肝细胞中会产生毒性作用，这通过监测天冬氨酸转氨酶（ASAT）的释放来评估。三氯一溴甲烷与四氯化碳具有同等毒性，而三氯甲烷则无活性，这表明毒性作用与溶剂性质无关。一氧化碳可显著降低四氯化碳介导的毒性，这表明可能是细胞色素P 450激活所致。测试了55种黄酮类化合物干扰四氯化碳诱导的ASAT释放的能力。这些化合物包括花青定醇、其3-醚和3-酯、黄烷酮、黄烷醇、黄酮和黄烷醇。亲水性更强的化合物可抑制四氯化碳诱导的毒性，而亲脂性衍生物则具有增强毒性的作用。未发现其他明显的构效关系。从这些化合物的作用机制以及该技术作为肝靶向药物筛选试验的有效性方面对结果进行了讨论。
