Hyperammonemia is a serious metabolic disorder associating with hepatic encephalopathy (HE) which occurs secondary to several forms of liver injury ranging from simple acute liver failure (ALF) to its most serious form; cirrhosis. The resent study highlights the possible ameliorative effect of oral nifuroxazide (25 mg/kg) against experimentally induced ALF and the subsequent HE in a well-standardized rat model. ALF and HE were induced in a rat model by I.P. injection of thioacetamide (TAA) (200 mg/kg) for 1 week at alternative days. Nifuroxazide administration for 14 days prior to and for further 7 days alongside TAA injection successfully attenuated TAA-induced ALF and HE; as demonstrated by the significant retraction in both brain and serum hyperammonemia with significant improvement in liver function biomarkers; ALT, AST, ALP, GGT, albumin, and serum total protein. This was associated with a significant restoration of both hepatic and brain oxidative stress incidences; MDA, SOD and catalase activities and GSH concentration. The observed improvement was associated with a significant reduction in liver and brain contents of c-Jun N-terminal kinase (cJNK); as an anti-inflammatory biomarker and a modulator of various pro- and anti-apoptotic proteins, caspase-8, and tumor necrosis factor-related apoptosis ligand (TRAIL); as biomarkers of apoptosis. In conclusion; the modulatory effect of nifuroxazide on cJNK/caspase-8/TRAIL signaling appears to underly its hepatoprotective effect and its ameliorative effect on HE progression.

中文翻译：

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尼呋拉嗪可减轻大鼠实验性肝性脑病及其相关的高氨血症和cJNK / caspase-8 / TRAIL的活化。

高氨血症是一种严重的代谢紊乱，与肝性脑病（HE）相关，继发于多种形式的肝损伤，从简单的急性肝衰竭（ALF）到最严重的肝损伤。肝硬化。最近的研究强调了在标准大鼠模型中口服尼呋沙嗪（25 mg / kg）对实验诱导的ALF和随后的HE可能具有改善作用。在大鼠模型中，在隔日注射IP硫代乙酰胺（TAA）（200 mg / kg）1周，从而诱导了ALF和HE。尼呋拉嗪在注射TAA之前的14天和另外7天与TAA注射一起成功地减弱了TAA诱导的ALF和HE。如脑和血清高氨血症的显着降低以及肝功能生物标志物的显着改善所证明；ALT，AST，ALP，GGT，白蛋白，和血清总蛋白。这与肝和脑氧化应激事件的显着恢复有关。MDA，SOD和过氧化氢酶活性以及GSH浓度。观察到的改善与c-Jun N端激酶（cJNK）的肝和脑内容物显着减少有关。作为抗炎生物标志物和多种促凋亡和抗凋亡蛋白，caspase-8和肿瘤坏死因子相关的凋亡配体（TRAIL）的调节剂；作为细胞凋亡的生物标志物。结论; 呋喃嗪对cJNK / caspase-8 / TRAIL信号传导的调节作用似乎是其肝保护作用及其对HE进程的改善作用。SOD和过氧化氢酶活性以及GSH浓度。观察到的改善与c-Jun N端激酶（cJNK）的肝和脑内容物显着减少有关。作为抗炎生物标志物和多种促凋亡和抗凋亡蛋白，caspase-8和肿瘤坏死因子相关的凋亡配体（TRAIL）的调节剂；作为细胞凋亡的生物标志物。结论; 呋喃嗪对cJNK / caspase-8 / TRAIL信号传导的调节作用似乎是其肝保护作用及其对HE进程的改善作用。SOD和过氧化氢酶活性以及GSH浓度。观察到的改善与c-Jun N端激酶（cJNK）的肝和脑内容物显着减少有关。作为抗炎生物标志物和多种促凋亡和抗凋亡蛋白，caspase-8和肿瘤坏死因子相关的凋亡配体（TRAIL）的调节剂；作为细胞凋亡的生物标志物。结论; 呋喃嗪对cJNK / caspase-8 / TRAIL信号传导的调节作用似乎是其肝保护作用及其对HE进程的改善作用。和肿瘤坏死因子相关的凋亡配体（TRAIL）；作为细胞凋亡的生物标志物。结论; 呋喃嗪对cJNK / caspase-8 / TRAIL信号传导的调节作用似乎是其肝保护作用及其对HE进程的改善作用。和肿瘤坏死因子相关的凋亡配体（TRAIL）；作为细胞凋亡的生物标志物。结论; 呋喃嗪对cJNK / caspase-8 / TRAIL信号传导的调节作用似乎是其肝保护作用及其对HE进程的改善作用。