Abstract
The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2′-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation.
Highlights
Aging causes progressive deterioration of organs, leading to impaired tissue function, increased vulnerability to stress, and death [1,2]
We hypothesized that resveratrol would attenuate the aging process in the kidney of mice by modulating renin-angiotensin system (RAS) components, especially by the activation of the ACE2/angiotensin 1-7 (Ang 1-7)/MasR axis, and we examined pro-inflammatory and antioxidant molecular changes in kidneys of aging mice
Changes in renal function of aging mice were measured, before and after resveratrol treatment, in renal function of aging micecontrol were measured, before and after resveratrol treatment, and Changes the results were compared with mice
Summary
Aging causes progressive deterioration of organs, leading to impaired tissue function, increased vulnerability to stress, and death [1,2]. The kidney is one of the most susceptible target organs of age-associated tissue damage [3], and the high incidence of chronic kidney disease, in the elderly, is a health problem, worldwide [4,5]. Various processes are involved in the deterioration seen in aging kidneys, including oxidative stress, mitochondrial dysfunction, inflammation, altered calcium regulation, and activation of the renin-angiotensin system (RAS) [6,7]. Nutrients 2018, 10, 1741 the classic RAS axis—angiotensin converting enzyme (ACE)/Ang II/AT1R. This axis suppresses pro-survival genes and enhances reactive oxygen species (ROS) and pro-inflammatory cytokines production, resulting in chronic inflammation and cell senescence [8,9].
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