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首页> 外文期刊>Journal of biochemical and molecular toxicology >Agmatine protects against sodium valproate-induced hepatic injury in mice via modulation of nuclear factor-kappa B/inducible nitric oxide synthetase pathway
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Agmatine protects against sodium valproate-induced hepatic injury in mice via modulation of nuclear factor-kappa B/inducible nitric oxide synthetase pathway

机译:通过调节核因子-Kappa B /诱导型一氧化氮合成酶途径,胍壶保护小鼠丙戊酸钠诱导的小鼠肝损伤

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摘要

Valproate is a widely used drug against epilepsy and several other neurological disorders although it has deleterious hepatotoxic side effects. The current study was designed to test if agmatine as nitric oxide modulator has protective effects against valproate-induced hepatic injury. Male Swiss albino mice were treated with sodium valproate (SVP) with or without agmatine for 7 days. Serum and liver samples were collected for analysis. Results have revealed that agmatine exerted hepatoprotective effects against SVP-associated hepatic injury. Agmatine ameliorated SVP-induced elevated serum biochemical markers of hepatic damage such as serum transaminases, alkaline phosphatase, gamma-glutamyl transferase, and lactate dehydrogenase. Histopathological examination of the liver showed improvement of hepatic lesions in case of agmatine treatment. Furthermore, agmatine attenuated oxidative stress and enhanced antioxidants in liver tissue. Agmatine inhibited the activation of nuclear factor-kappa B and ameliorated the immunoexpression of inducible nitric oxide synthetase. This was accompanied by decrease in the level of inflammatory markers as nitrite/nitrate, tumor necrosis factor-alpha, and interleukin-6. These data provide new evidence of the hepatoprotective activity of agmatine against SVP-induced hepatotoxic effects.
机译:戊甲酸是一种广泛使用的药物针对癫痫和其他几种神经系统疾病,尽管它具有有害的肝毒性副作用。目前的研究旨在测试Agmatine作为一氧化氮调节剂是否对Valproate诱导的肝损伤具有保护作用。将雄性瑞士白化小鼠用丙酸钠(SVP)用或没有杏仁酸钠处理7天。收集血清和肝脏样品进行分析。结果表明,毒素对SVP相关的肝损伤施加肝脏保护作用。 Agmatine改善SVP诱导的肝损伤的升高的血清生物化学标记,如血清转氨酶,碱性磷酸酶,γ-戊二醇转移酶和乳酸脱氢酶。肝脏的组织病理学检查表明,在龟氨酸处理的情况下,肝脏病变的改善。此外,Agmatine在肝组织中减毒氧化应激和增强的抗氧化剂。 Agmatine抑制核因子-Kappa B的激活并改善了诱导型一氧化氮合成酶的免疫表达。这伴随着炎症标志物水平的降低,作为亚硝酸盐/硝酸盐,肿瘤坏死因子-α和白细胞介素-6。这些数据提供了针对SVP诱导的肝毒性作用的抗麦木的肝脏保护活性的新证据。

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