Albeltagy Rasha S, Mumtaz Farah, Abdel Moneim Ahmed E, El-Habit Ola H
Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.
Biol Trace Elem Res. 2021 Dec;199(12):4657-4665. doi: 10.1007/s12011-021-02591-8. Epub 2021 Jan 17.
We performed a thorough screening and analysis of the impact of cadmium chloride (CdCl) and N-acetylcysteine (NAC) on the miR146a/NF-κB p65 inflammatory pathway and mitochondrial biogenesis dysfunction in male albino rats. A total of 24 male albino rats were divided into three groups: a control group, a CdCl-treated group (3 mg/kg, orally), and a CdCl + NAC-treated group (200 mg/kg of NAC, 1 h after CdCl treatment), for 60 consecutive days. Real-time quantitative PCR was used to analyze the expression of miR146a, Irak1, Traf6, Nrf1, Nfe2l2, Pparg, Prkaa, Stat3, Tfam, Tnfa, and Il1b, whereas tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 protein levels were assessed using ELISA, and NF-κB p65 was detected using western blotting. A significant restoration of homeostatic inflammatory processes as well as mitochondrial biogenesis was observed after NAC and CdCl treatment. Decreased miR146a and NF-κB p65 were also found after treatment with NAC and CdCl compared with CdCl treatment alone. Collectively, our findings demonstrate that CdCl caused mtDNA release because of Tfam loss, leading to NF-κB p65 activation. Co-treatment with NAC could alleviate Cd-induced genotoxicity in liver tissue. We concluded that adding NAC to CdCl resulted in a decreased signaling of the NF-κB p65 signaling pathway.
我们对氯化镉（CdCl）和N-乙酰半胱氨酸（NAC）对雄性白化大鼠miR146a/NF-κB p65炎症通路及线粒体生物发生功能障碍的影响进行了全面筛查和分析。总共24只雄性白化大鼠被分为三组：对照组、CdCl处理组（口服3 mg/kg）和CdCl + NAC处理组（CdCl处理1小时后给予200 mg/kg NAC），连续处理60天。采用实时定量PCR分析miR146a、Irak1、Traf6、Nrf1、Nfe2l2、Pparg、Prkaa、Stat3、Tfam、Tnfa和Il1b的表达，使用酶联免疫吸附测定（ELISA）评估肿瘤坏死因子-α、白细胞介素-1β和环氧化酶-2蛋白水平，采用蛋白质印迹法检测NF-κB p65。NAC和CdCl处理后观察到稳态炎症过程以及线粒体生物发生有显著恢复。与单独CdCl处理相比，NAC和CdCl处理后还发现miR146a和NF-κB p65降低。总体而言，我们的研究结果表明，CdCl由于Tfam缺失导致线粒体DNA释放，从而导致NF-κB p65激活。NAC联合处理可减轻Cd诱导的肝脏组织遗传毒性。我们得出结论，在CdCl中添加NAC可导致NF-κB p65信号通路的信号传导减少。
