Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats
Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats
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DOI：
10.3109/01480549709003881
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发表时间：
1997-01-01
影响因子：
2.6
通讯作者：
Mehta, S
中科院分区：
文献类型：
--
作者：
Sodhi, CP;Rana, SV;Mehta, S
本文研究了氧化应激在异烟肼（INH）和利福平（RMP）合用引起幼鼠肝毒性中的作用。通过在两周内给予INH和RMP各50 mg/kg/天来产生成功的肝毒性模型。肝脏显示II型肝细胞变化（微泡脂肪沉积），伴轻度门静脉三尖瓣炎。INH和RMP联合治疗可显著降低血液和肝组织中谷胱甘肽和相关硫醇的含量。超氧化物歧化酶，谷胱甘肽过氧化物酶，过氧化氢酶和谷胱甘肽-S-转移酶与CDNB和DCNB作为底物，减少，联合治疗组。谷胱甘肽还原酶、以依他尼酸为底物的谷胱甘肽-S-转移酶和脂质过氧化反应均随处理的进行而显著增加。抗氧化酶谱的改变与脂质过氧化作用的增加表明INH和RMP处理的组合增强了氧化应激。除超氧化物歧化酶在血液组织中显示显著增强外，所有结果均如实反映在血液组织中。因此，INH和RMP肝毒性似乎是通过氧化应激介导的。
The role of oxidative-stress as a mechanism of hepatotoxicity caused by combination of isoniazid (INH) and Rifampicin (RMP) was investigated in young growing rats. A successful model of hepatotoxicity was produced by giving 50 mg/kg/day each of INH and RMP in two weeks. Liver showed type II hepatocellular changes (microvesicular fat deposition) with mild portal triaditis. The glutathione and related thiols were significantly decreased in both blood and fiver tissues with combination of INH and RMP treatment. Superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferases with CDNB and DCNB as substrates were decreased in the, combination treated group. Glutathione reductase, glutathione-S-transferase with ethacrynic acid as substrate and lipid peroxidation exhibited a significant increase with treatment. The altered profile of antioxidant enzymes with increased lipid peroxidation indicated the enhanced oxidative-stress in combination of INH and RMP treatment. All the findings are faithfully reflected in the blood tissue except superoxide dismutase which showed significant enhancement in this tissue. INH and RMP hepatotoxicity is thus appeared to be mediated through oxidative-stress.