San-Miguel B, Alvarez M, Culebras J M, González-Gallego J, Tuñón M J
Department of Physiology, University of León, 24071, León, Spain.
Apoptosis. 2006 Nov;11(11):1945-57. doi: 10.1007/s10495-006-0090-0.
This work was undertaken to investigate whether treatment with N-acetyl-cysteine (NAC) prevents oxidative stress and inhibits the apoptotic pathways in an animal model of fulminant hepatic failure.
Rabbits were experimentally infected with 2x10(4) hemagglutination units of a rabbit hemorrhagic disease virus isolate.
The spontaneous mortality rate of infected animals was 67% at 36 h post infection (pi) and 90% at 48 h pi. This percentage decreased significantly in animals receiving an i.p. injection of NAC (150 mg/kg body way/daily), for 7 days prior to infection. From 36 h pi marked increases were detected in blood levels of transaminases, lactate dehydrogenase, bilirubin and the oxidised/reduced glutathione ratio. All these effects were significantly prevented by NAC treatment. The Bax to Bcl-2 relative expression, the expression of FasL, cytochrome c and PARP-1, and the activity of caspase 3 were significantly increased at 36 and 48 h pi in infected animals. These changes were markedly reduced in animals treated with NAC, with the exception of FasL.
Our results suggest a potential hepatoprotective role of NAC in fulminant hepatic failure, mediated partially through the modulation of the intrinsic pathway of apoptosis.
本研究旨在探讨在暴发性肝衰竭动物模型中，N-乙酰半胱氨酸（NAC）治疗是否能预防氧化应激并抑制凋亡途径。
用2×10⁴血凝单位的兔出血病病毒分离株对家兔进行实验性感染。
感染动物在感染后（pi）36小时的自发死亡率为67%，48小时时为90%。在感染前7天每天腹腔注射NAC（150mg/kg体重）的动物中，这一百分比显著降低。从感染后36小时起，转氨酶、乳酸脱氢酶、胆红素水平以及氧化型/还原型谷胱甘肽比值在血液中显著升高。NAC治疗可显著预防所有这些效应。在感染动物中，感染后36小时和48小时时，Bax与Bcl-2相对表达、FasL、细胞色素c和PARP-1的表达以及caspase 3的活性显著增加。除FasL外，NAC治疗的动物中这些变化明显减少。
我们的结果表明NAC在暴发性肝衰竭中具有潜在的肝保护作用，部分是通过调节凋亡的内在途径介导的。
