This study examined the effect of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) inhibitor, on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) in mice. UUO led to a significant increase in the fibrotic area of obstructed kidneys, which was attenuated by NAC (84.8 mg/kg/d) in the drinking water. Renal expression of type III collagen and tumor necrosis factor (TNF)-α mRNAs was elevated in UUO mice and inhibited by NAC. Extracellular signal-regulated kinase (ERK1/2) phosphorylation was significantly elevated by UUO, and NAC significantly attenuated the elevation. UUO inhibited the activity of glutathione peroxidase, while NAC restored its activity. Together, the results of this study suggest that renal interstitial fibrosis induced by UUO was ameliorated by NAC via several mechanisms including increased glutathione peroxidase activity, reduced phosphorylation of ERK1/2, and reduced expression of TNF-α and type III collagen mRNAs.
Keywords: N-acetyl cysteine; extracellular signal-regulated kinase; fibrosis; glutathione peroxidase; tumor necrosis factor (TNF)-α; type III collagen.