Angiotensin-(1-7) attenuates collagen-induced arthritis via inhibiting oxidative stress in rats

The present study was designed to investigate the anti-rheumatic effects and the mechanism of angiotensin (Ang)-(1-7) in rat models with collagen-induced arthritis (CIA). The CIA model was established using male Wistar rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of the tail. The levels of angiotensin converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor (MasR) were reduced in CIA rats. The attenuation of paw swelling and arthritis scores and improvement of indexes of spleen and thymus were done by Ang-(1-7) injection in CIA rats. The increased levels of inflammatory cytokines, such as interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma in the serum and hind paw were blocked by Ang-(1-7) administration. In addition, enhanced NADPH oxidase (Nox) activity, increased levels of superoxide anions and malondialdehyde (MDA), and weakened superoxide dismutase (SOD) activity, were all reversed by treatment with Ang-(1-7). Nox1 overexpression reversed the suppressing effects of Ang-(1-7) on paw swelling and arthritis scores in CIA rats. The Ang-(1-7)-induced improvement in spleen and thymus indexes in CIA rats was abolished by Nox1 overexpression. Nox1 overexpression reversed the inhibitory effects of Ang-(1-7) by increasing IL-1 beta, IL-6, TNF-alpha, and IFN-gamma levels in the serum and hind paw of CIA rats. These results demonstrated that Nox1 increased the oxidative stress in arthritis, and Ang-(1-7) improved rheumatism in arthritis via inhibiting oxidative stress.