Isoniazid- and rifampicin-induced oxidative hepatic injury -: protection by N-acetylcysteine
Isoniazid- and rifampicin-induced oxidative hepatic injury -: protection by N-acetylcysteine
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DOI：
10.1191/096032700674230830
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发表时间：
2000-09-01
影响因子：
2.8
通讯作者：
Singh, K
中科院分区：
文献类型：
--
作者：
Attri, S;Rana, SV;Singh, K
本文研究了谷胱甘肽（GSH）前体N-乙酰半胱氨酸（NAC）对异烟肼（INH）和利福平（RIF）诱导的幼年Wistar大鼠氧化性肝损伤的保护作用。INH和RIF的肝毒性剂量均为50 mg/kg·d（-1），NAC的肝保护剂量为100 mg/kg·d（-1）。所有药物均经腹膜内（i. p.）在无菌水中（4.0 ml k（-1）day（-1）），持续3周。氧化/抗氧化特征的状态是评估肝毒性和/或肝保护的机制方法。INH-RIF联合暴露动物的氧化损伤与GSH和相关硫醇的显著下降以及抗氧化酶系统受损密切相关。在这些动物中观察到的脂质过氧化增加进一步支持了氧化应激。NAC联合给药可预防INH-RIF联合暴露动物中氧化应激的诱导。NAC对氧化应激的改善如实反映为这些动物中的正常形态，除了在一只共暴露于INH-RIF和NAG的动物中存在轻度的门静脉三尖瓣炎。相比之下，单独共暴露于INH-RIF的动物显示出从小叶内炎症到斑片状坏死的组织学病变。这些结果表明，INH-RIF诱导的氧化损伤可以通过NAG支持细胞的抗氧化防御机制来预防。
The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid- (INH) and rifampicin- (RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg(-1) day(-1) each and the hepatoprotective dose of NAC was 100 mg kg(-1) day(-1). All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml k(-1) day(-1)) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAG. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAG.