异烟肼和利福平合用及异烟肼代谢物对人肝细胞的毒性作用

Cellular toxicity of isoniazid used together with rifampicin and the metabolites of isoniazid on QSG-7701 hepatocytes

目的:探讨异烟肼、利福平单用和合用及异烟肼代谢物对培养人肝细胞的毒性作用。方法:将培养的QSG-7701人肝细胞培养液中分别加入异烟肼、利福平、异烟肼+利福平、异烟肼代谢物乙酰肼、肼后继续培养48h。用四甲基偶氮唑盐(MTT)法测定药物处理后肝细胞的存活率;药物处理后分别收集培养液和细胞,将细胞裂解后,用比色法分别测定培养液和细胞裂解液中的乳酸脱氢酶的活性。结果:与对照组比较,异烟肼、乙酰肼、肼、利福平及利福平和异烟肼合用均使肝细胞存活率显著降低和乳酸脱氢酶释放显著增加;利福平和异烟肼合用导致细胞存活率降低和乳酸脱氢酶释放增加的毒性剂量低于其单用的毒性剂量;异烟肼代谢物肼在低浓度即产生明显的细胞毒性。结论:利福平和异烟肼合用及异烟肼代谢物肼对人肝细胞具有细胞毒性作用,其中肼的肝细胞毒性作用最强。

OBJECTIVE To investigate the cellular toxicity of rifampicin used together with rifampicin and the metabolites of isoniazid on cultured QSG-771）1 cells lines. METHODS lsoniazid, rifampicin, rifampicin and isoniazid, acetylhydrazine, hydrazine were added in cultural media of QSG-7701 cells and cultured for 48 hours. The survival rate of cells were determined by MTT method. The cultural media and ceils were collected and the activity of lactate dehydrogenase were detected with chroma tometry. RESULTS Compared with control group, the survival rate decreased significantly and the lactate dehydrogenase released from cell increased significantly in cells treated with isoniazid, rifampicin, acetylhydrazine, hydrazine. Hydrazine, the metabolite of isoniazid produced significant damage on hepatocytes in low concentration. CONCLUSION Rifampicin used to gether with rifampicin and metabolites of isoniazid produced cellular toxic effects and hydrazine may be the most toxiferous me tabolite.