Khalaf A A, Zaki A R, Galal M K, Ogaly H A, Ibrahim M A, Hassan A
1 Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
2 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni Suef Governorate, Egypt.
Hum Exp Toxicol. 2017 Sep;36(9):881-891. doi: 10.1177/0960327116674526. Epub 2016 Nov 12.
The present research task is aimed to evaluate the role of exogenous α-lipoic acid (ALA) (100 mg/kg body weight) as hepatoprotective and potent antioxidant in amelioration of copper nanoparticle (CNP)-induced hepatotoxicity. Forty male rats were randomly assigned into four equal groups: group I (control), group II received CNPs, group III received CNPs + ALA, and finally group IV received ALA for 2 months. At the end of the experimental period, the rats were decapitated, and blood and liver tissue samples were collected for measurement of liver function tests, antioxidant status, lipid peroxidation (LPO), copper content, expression of some apoptotic genes, and histopathological analysis. CNPs induced marked hepatic damages as evident by severe alteration in hepatic biomarkers. This was accompanied by a significant elevation in hepatic LPO and induced nitric oxide, copper content, and expression level of apoptotic genes (C-myc and C-jun). In contrast, marked depletion for antioxidant parameters was detected. These findings were confirmed with severe pathological alterations. Coadministration of ALA as a powerful antioxidant attenuates the hepatotoxic effects of CNPs through improvement of liver parameters, oxidative status, genetic changes, and preservation of liver integrity through histopathological analysis. These results suggest that consumed ALA could be used as an applicable hepatoprotective agent against oxidative damage mediated by nanoparticles intoxication.
本研究任务旨在评估外源性α-硫辛酸(ALA)(100毫克/千克体重)作为肝保护剂和强效抗氧化剂在改善铜纳米颗粒(CNP)诱导的肝毒性中的作用。将40只雄性大鼠随机分为四组,每组数量相等:第一组(对照组),第二组接受CNP,第三组接受CNP + ALA,最后第四组接受ALA,持续2个月。在实验期结束时,将大鼠断头,并采集血液和肝脏组织样本,用于测量肝功能测试、抗氧化状态、脂质过氧化(LPO)、铜含量、一些凋亡基因的表达以及组织病理学分析。CNP诱导了明显的肝脏损伤,肝脏生物标志物的严重改变证明了这一点。这伴随着肝脏LPO的显著升高以及诱导型一氧化氮、铜含量和凋亡基因(C-myc和C-jun)表达水平的升高。相反,检测到抗氧化参数明显降低。这些发现通过严重的病理改变得到证实。作为强效抗氧化剂的ALA共同给药通过改善肝脏参数、氧化状态、基因变化以及通过组织病理学分析保持肝脏完整性,减轻了CNP的肝毒性作用。这些结果表明,摄入的ALA可作为一种适用的肝保护剂,用于对抗纳米颗粒中毒介导的氧化损伤。