N-Acetylcysteine Reduces miR-146a and NF-κB p65 Inflammatory Signaling Following Cadmium Hepatotoxicity in Rats.

We performed a thorough screening and analysis of the impact of cadmium chloride (CdCl2) 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 CdCl2-treated group (3 mg/kg, orally), and a CdCl2 + NAC-treated group (200 mg/kg of NAC, 1 h after CdCl2 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 CdCl2 treatment. Decreased miR146a and NF-κB p65 were also found after treatment with NAC and CdCl2 compared with CdCl2 treatment alone. Collectively, our findings demonstrate that CdCl2 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 CdCl2 resulted in a decreased signaling of the NF-κB p65 signaling pathway.