Protective effect of N-acetylcysteine and defeyoxamine on carbon tetrachloride-induced acute hepatic failure in rats
Protective effect of N-acetylcysteine and defeyoxamine on carbon tetrachloride-induced acute hepatic failure in rats
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DOI：
10.1097/01.ccm.0000142699.54266.d9
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发表时间：
2004-10-01
影响因子：
8.8
通讯作者：
Dal-Pizzol, F
中科院分区：
文献类型：
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作者：
Ritter, C;Reinke, A;Dal-Pizzol, F
目的：四氯化碳（CCl4）是一种脂溶性强肝毒性物质；因此，它被广泛用作严重肝功能衰竭的动物模型。抗氧化剂治疗可能会调节CCl4对肝脏的毒性作用，通常在CCl4之前给药，这可能限制其在临床环境中的使用。我们在这里描述了n -乙酰半胱氨酸、去铁胺或两者在治疗ccl4诱导的肝衰竭中的作用。设计：前瞻性、随机、对照实验。单位：动物基础科学实验室。实验对象：雄性Wistar大鼠，体重200-250 g。干预措施：暴露于CCl4的大鼠用n -乙酰半胱氨酸和/或去铁胺或载体治疗。测量结果和主要结果：n -乙酰半胱氨酸联合去铁胺治疗显著减轻CCl4急性肝衰竭后肝脏和中枢神经系统的氧化损伤。此外，n -乙酰半胱氨酸+去铁胺组血清丙氨酸氨基转移酶、总胆红素、凝血酶原时间均显著低于n -乙酰半胱氨酸、去铁胺和生理盐水组。经n -乙酰半胱氨酸加去铁胺治疗后，肝细胞坏死和四氯化碳引起的炎症浸润明显减轻。未治疗大鼠的存活率为5%。n -乙酰半胱氨酸和去铁胺治疗的生存率分别提高到25%和35%。用n -乙酰半胱氨酸加去铁胺治疗的大鼠存活率为80%。结论：我们的数据首次提供了实验证明n -乙酰半胱氨酸加去铁胺可降低大鼠死亡率，降低氧化应激，并限制CCl4诱导的炎症浸润和肝细胞坏死。
Objective: Carbon tetrachloride (CCl4) is a lipid-soluble potent hepatotoxic; thus, it widely is used as an animal model of severe hepatic failure. Treatment with antioxidants may modulate the toxic effects of CCl4 on liver, generally with drug administration before CCl4, which can restrict its use in the clinical setting. We here describe the effects of N-acetylcysteine, deferoxamine, or both in the treatment of CCl4-induced hepatic failure.Design: Prospective, randomized, controlled experiment.Setting: Animal basic science laboratory.Subjects: Male Wistar rats, weighing 200-250 g.Interventions: Rats exposed to CCl4 were treated with N-acetylcysteine and/or deferoxamine or vehicle.Measurements and Main Results: N-acetylcysteine plus deferoxamine treatment significantly attenuated hepatic and central nervous system oxidative damage after acute hepatic failure induced by CCl4. In addition, the serum levels of alanine amino-transferase, total bilirubin, and prothrombin time in the N-acetylcysteine plus deferoxamine group were significantly lower than those in the N-acetylcysteine or deferoxamine and saline groups. After N-acetylcysteine plus deferoxamine treatment, hepatocellular necrosis and inflammatory infiltration induced by carbon tetrachloride were greatly decreased. Survival in untreated rats was 5%. Survival increased to 25% and 35%, respectively, with N-acetylcysteine and deferoxamine treatment. In rats treated with N-acetylcysteine plus deferoxamine, survival was 80%.Conclusions: Our data provide the first experimental demonstration that N-acetylcysteine plus deferoxamine reduces mortality rate, decreases oxidative stress, and limits inflammatory infiltration and hepatocyte necrosis induced by CCl4 in the rat.