N-acetylcysteine alleviates angiotensin II-mediated renal fibrosis in mouse obstructed kidneys

• Published in: Acta pharmacologica Sinica Vol. 37; no. 5; pp. 637 - 644
• Main Authors: Shen, Yang, Miao, Nai-jun, Xu, Jin-lan, Gan, Xin-xin, Xu, Dan, Zhou, Li, Xue, Hong, Zhang, Wei, Lu, Li-min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2016; Nature Publishing Group
• Subjects: Acetylcysteine - pharmacology; Acetylcysteine - therapeutic use; Angiotensin II - metabolism; Angiotensin II - pharmacology; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cell Line; Fibroblasts - drug effects; Fibroblasts - pathology; Fibrosis - drug therapy; Fibrosis - etiology; Fibrosis - pathology; Immunology; Internal Medicine; Kidney - drug effects; Kidney - pathology; Kidney Diseases - drug therapy; Kidney Diseases - etiology; Kidney Diseases - pathology; Male; Medical Microbiology; Mice, Inbred C57BL; N-乙酰半胱氨酸; Original; original-article; Oxidative Stress; Pharmacology/Toxicology; Reactive Oxygen Species - metabolism; Renin-Angiotensin System - drug effects; Ureteral Obstruction - complications; Ureteral Obstruction - drug therapy; Ureteral Obstruction - pathology; Vaccine; 介导; 小鼠; 成纤维细胞; 梗阻; 纤维化; 肾脏; 血管紧张素II; acetylcysteine; chronic kidney disease; angiotensin II; rat renal fibroblast NRK-49F cells; ROS; unilateral ureteral obstruction; renal fibrosis; oxidative stress
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/aps.2016.12

Aim： To investigate the effects of ROS scavenger N-acetylcysteine （NAC） on angiotensin II （Ang II）-mediated renal fibrosis in vivo and in vitro. Methods： Mice were subjected to unilateral ureteral obstruction （UUO）, and then treated with vehicle or NAC （250 mg/kg, ip） for 7 days. Histological changes of the obstructed kidneys were observed with Masson＇s trichrome staining. ROS levels were detected with DHE staining. The expression of relevant proteins in the obstructed kidneys was assessed using Western blotting assays. Cultured rat renal fibroblast NRK-49F cells were used for in vitro experiments. Results： In the obstructed kidneys, Ang II levels were significantly elevated, and collagen I was accumulated in the interstitial spaces. Furthermore, ROS production and the expression of p47 （a key subunit of NADPH oxidase complexes） were increased in a time- dependent manner; the expression of fibronectin, α-SMA and TGF-β were upregulated. Administration of NAC significantly alleviated the fibrotic responses in the obstructed kidneys. In cultured NRK-49F cells, treatment with Ang II （0.001-10 pmol/L） increased the expression of fibronectin, collagen I, α-SMA and TGF-β in dose-dependent and time-dependent manners. Ang II also increased ROS production and the phosphorylation of Smad3. Pretreatment with NAC （5 pmol/L） blocked Ang II-induced oxidative stress and ECM production in the cells. Conclusion＂ In mouse obstructed kidneys, the fibrotic responses result from Ang II upregulation can be alleviated by the ROS scavenger N-acetylcysteine.