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

Abstract

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.

Keywords: Cadmium chloride; NAC; NF-κB p65; Tumorigenesis; miR146-a.