Awodele Olufunsho, Agbaje Esther O, Adesina Enitan A, Akintonwa Alade
Department of Pharmacology, College of Medicine, University of Lagos, Nigeria.
Tokai J Exp Clin Med. 2011 Jul 20;36(2):31-6.
Advent of the HIV/AIDS pandemic has led to a dramatic increase in the number of TB cases worldwide. Availability of highly active antiretroviral therapy (HAART) has significantly improved the outcome of HIV/AIDS, in terms of prevention of opportunistic infections (OIs) as well as mortality however; liver toxicity is one of the most relevant adverse effects of antiretroviral therapy (ART).
In view of the inevitable use of zidovudine (a common ART) and antituberculous fixed-dose combination therapy (FDCs) in the management of HIV-TB co-infection and the resultant hepatotoxicity, this study was aimed to investigate the hepatoprotective role of neutrosec (a combination of aminoacid and vitamins) on the hepatotoxicity induced by co-administration of zidovudine and combined fixed dose antituberculous agents.
Twenty four rats were randomly allotted to four groups, consisting of the control, zidovudine plus fixed dose combined anti TB agents treated group, zidovudine plus fixed dose combined anti TB agents plus neutrosec treated group and neutrosec alone treated group. Therapeutic doses of zidovudine (8.5 mg/kg/day), fixed dose combined anti TB agents (25 mg/kg/day) and neutrosec (0.4 ml/kg/day) were administered to the animals via oral gavage, daily over 60 days. After 60 days, rats were sacrificed for internal macroscopic and histological examination of the liver. The liver enzyme parameters (AST, ALP, Total bilirubin, Total protein, Albumin) were determined using fully automated clinical chemistry analyzer (Hitachi 912, Boehringer Mannheim, Germany). Antioxidant enzymes activity and lipid peroxidation were determined according to standard procedures.
The AST results showed a significant (p ≤ 0.05) decreased in the zidovudine plus anti-TB plus neutrosec treated group (125.50 ± 22.71) compared with zidovudine plus anti-TB treated group (399. 10 ± 0.45). It further showed non-significant decreased (p ≥ 0.05) in the ALP levels between the zidovudine plus anti TB treated group (317.10 ± 73.48) and the zidovudine plus anti TB plus neutrosec treated group (203.20 ± 35.97). There was a non-significant (p ≤ 0.05) decrease in the MDA level of the zidovudine plus anti-TB plus neutrosec treated group compared with the zidovudine plus anti-TB treated group.
The hepatotoxic effect of zidovudine plus combined anti TB drugs which may be due to free radical generation was modulated by neutrosec.
艾滋病大流行导致全球结核病病例数急剧增加。高效抗逆转录病毒疗法（HAART）的出现显著改善了艾滋病毒/艾滋病的治疗效果，在预防机会性感染（OIs）以及降低死亡率方面均有成效；然而，肝毒性是抗逆转录病毒疗法（ART）最相关的不良反应之一。
鉴于在治疗艾滋病毒与结核病合并感染时不可避免地会使用齐多夫定（一种常见的抗逆转录病毒药物）和抗结核固定剂量复方疗法（FDCs），以及由此产生的肝毒性，本研究旨在探讨中性sec（一种氨基酸和维生素的组合）对齐多夫定与抗结核固定剂量复方制剂联合使用所诱导的肝毒性的肝保护作用。
将24只大鼠随机分为四组，分别为对照组、齐多夫定加固定剂量抗结核联合制剂治疗组、齐多夫定加固定剂量抗结核联合制剂加中性sec治疗组和单独使用中性sec治疗组。通过口服灌胃法，每天给动物施用治疗剂量的齐多夫定（8.5毫克/千克/天）、固定剂量抗结核联合制剂（25毫克/千克/天）和中性sec（0.4毫升/千克/天），持续60天。60天后，处死大鼠以对肝脏进行内部大体和组织学检查。使用全自动临床化学分析仪（德国勃林格殷格翰公司的日立912）测定肝酶参数（AST、ALP、总胆红素、总蛋白、白蛋白）。根据标准程序测定抗氧化酶活性和脂质过氧化。
与齐多夫定加抗结核治疗组（399.10±0.45）相比，齐多夫定加抗结核加中性sec治疗组（125.50±22.71）的AST结果显示显著降低（p≤0.05）。齐多夫定加抗结核治疗组（317.10±73.48）和齐多夫定加抗结核加中性sec治疗组（203.20±35.97）之间的ALP水平进一步显示无显著降低（p≥0.05）。与齐多夫定加抗结核治疗组相比，齐多夫定加抗结核加中性sec治疗组的MDA水平有不显著降低（p≤0.05）。
中性sec调节了齐多夫定加抗结核联合药物可能因自由基产生而导致的肝毒性作用。
