Rodríguez J A, Haun M
Instituto de Biologia Vegetal y Biotecnología, Universidad de Talca, Chile.
Planta Med. 1999 Aug;65(6):522-6. doi: 10.1055/s-1999-14008.
The cytotoxicity of trans-dehydrocrotonin (DHC), an antiulcerogenic diterpene from Croton cajucara (Euphorbiaceae), was assessed on a V79 fibroblast cell line and on rat hepatocytes. Three independent endpoints for cytotoxicity were evaluated: DNA content, MTT reduction and neutral red uptake (NRU). For the V79 cells IC50 values of 253 and 360 microM were obtained for the NRU and MTT tests. The cytotoxic effect of DHC was time exposure dependent and no ability to recover after treatment was observed. For the rat hepatocytes IC50 values of 8, 300 and 400 microM for the MTT, DNA and NRU assays were obtained. The greater toxicity observed for the MTT test was inhibited when the experiment was performed using non-fresh hepatocytes in an age-dependent fashion. The treatment of V79 cells with the conditioned medium resulting after hepatocyte incubation with DHC showed an enhancement of MTT reduction without any evident toxic effects on fibroblasts. These results suggest that DHC has basal cytotoxic effects as observed on V79 fibroblasts and expresses a selective cytotoxicity after its metabolization by the hepatocytes. The bioactivation of DHC is mediated by cytochrome P450 and could generate metabolites that have no toxicity for V79 fibroblasts.
反式脱氢巴豆素（DHC）是一种来自大戟科卡朱卡拉巴豆的具有抗溃疡作用的二萜类化合物，对V79成纤维细胞系和大鼠肝细胞的细胞毒性进行了评估。评估了细胞毒性的三个独立终点：DNA含量、MTT还原和中性红摄取（NRU）。对于V79细胞，NRU和MTT试验的IC50值分别为253和360 microM。DHC的细胞毒性作用具有时间暴露依赖性，且处理后未观察到恢复能力。对于大鼠肝细胞，MTT、DNA和NRU试验的IC50值分别为8、300和400 microM。当使用非新鲜肝细胞以年龄依赖性方式进行实验时，MTT试验中观察到的更大毒性受到抑制。用DHC孵育肝细胞后产生的条件培养基处理V79细胞，显示MTT还原增强，对成纤维细胞无明显毒性作用。这些结果表明，DHC对V79成纤维细胞具有基础细胞毒性作用，并且在被肝细胞代谢后表现出选择性细胞毒性。DHC的生物活化由细胞色素P450介导，可能产生对V79成纤维细胞无毒性的代谢产物。
