The renin-angiotensin system plays an important role in the aging process of kidney through increased tissue reactive oxygen species production and progressively increased oxidative stress. In the present study, we aimed to evaluate the effect of resveratrol, a naturally found polyphenol with variety of bioactivities, including antioxidant, anti-inflammatory, anti-senescent activity, in modulation of renin-angiotensin system in aging kidney of mice.Design and Method:
18-month-old male C57BL/6 mice were divided into two groups and received either normal chow (Cont.) or underwent resveratrol (RSV) treatment for 6 months. Intrarenal expression of angiotensin II (ANGII), angiotensin II type 1 receptors (AT1R), angiotensin II type 2 receptors (AT2R), angiotensin converting enzyme (ACE) and ACE2, as well as pro- and antioxidant enzymes (endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosin, superoxide dismutase 1 and 2 (SOD1 and SOD2), fibronectin, collagen IV, and transforming growth factor-β) were measured, and mice kidney was isolated for histological assays.Results:
Resveratrol-treated group showed significant improvement in serum creatinine (Cont.: 0.67 ± 0.34 mg/dL vs. RSV: 0.25 ± 0.05 mg/dL, p = 0.03), creatinine clearance (Cont.: 0.10 ± 0.04 ml/min vs. RSV: 0.28 ± 0.07 ml/min, p = 0.001), albuminuria (Cont.: 67.69 ± 22.79 μg/24hr vs. RSV: 29.47 ± 14.32 μg/24hr, p = 0.008), glomerulosclerosis and tubular interstitial fibrosis compared with control group. The expressions of AngII, ACE and AT1R significantly decreased in resveratrol-treated group, whereas those of ACE2, AT2R and MasR increased. Resveratrol increased the expression of phosphorylated eNOS significantly and SOD1 and SOD2 were also increased but there was no statistical meaning. The expressions of fibronectin and collagen IV significantly decreased and while the expression of Nox4 significantly decreased, that of Nox2 did not change. Immunohistochemistry revealed that the 8-OHdG-positive area and the 3-nitrotyrosin-positive area decreased in resveratrol-treated group.Conclusions:
Resveratrol exerts renoprotective effects on aging kidney, associated with reduction of oxidative stress, inflammation and fibrosis through AT2R and MasR activation.