环丙沙星与氧氟沙星联用抗结核药物肝毒性比较

Comparison of hepatic toxic injury induced by combining ciproxacin or ofloxacin with Antituberculosis drugs in mice

目的 研究环丙沙星或氧氟沙星联用抗结核药的肝毒性并探讨其机制。方法 分别测定异烟肼和利福平联合用药 (IR)组及其分别联用氧氟沙星 (IRO)或环丙沙星 (IRC)组小鼠的血清谷氨酸氨基转移酶 (ALT)、肝指数、肝匀浆丙二醛 (MDA)含量、肝微粒体细胞色素P45 0和线粒体Ca2 + ATP酶活性 ,及肝病理检查 ,结果与对照组以及实验组之间进行比较。结果 与正常对照组比较 ,IR组及IRO组的血清ALT、肝细胞匀浆MDA明显增高 (P <0 .0 5 ) ,而IRC组变化不大 (P >0 .0 5 ) ;同时发现IR组和IRO组的肝微粒体细胞色素P45 0含量较高和线粒体Ca2 +ATP酶活性较低 ,而IRC组则相反 ;病理检查IRO和IRC组肝细胞坏死程度稍轻但与IR组比较无明显差异。结论 氧氟沙星、环丙沙星不增加异烟肼和利福平联用肝毒性 ,且环丙沙星有一定的拮抗作用。

Objective To compare hepatic toxic injury induced by combining ciproxacin or ofloxacin with isoniazid and rifampicin in mice. Methods The level of serum glutamic pyruvic transaminase(ALT),liver index, content of malondialdhyde (MDA) of liver homogenate, activity of hepatic microsome enzyme and mitochondrial membrane Ca 2+ ATP enzyme, and degree of liver cell injury were investigated in mice which were in control group and the experimental groups of combining isoniazid with rifampicin(IR),combining ofloxacin with isoniazid and rifampicin(IRO),combining ciproxacin with isoniazid and rifampicin(IRC). Results the groups of IR,IRO could markedly increase the level of ALT, and content of MDA of liver homogenate ( P <0.05) and decrease the activity of mitochondrial membrane Ca 2+ ATP enzyme( P >0.05), but IRC didn't induce these alterations, IR, IRO, IRC could increase the degree of liver injury, but there was no difference among the groups of IR,IRO,IRC . Conclusions Combining of loxacin or ciproxacin with isoniazid and rifampicin in mice could not increase hepatic toxic injury induced by combining isoniazid with rifampicin, but considering the level of injury, compairing with ofloxacin, ciproxacin was a little lower.