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The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on sodium and water transporters, in the kidneys of aged rats. Normal, 8-month-old male Wistar rats were treated (n=6) or not (n=6) with NAC (600 mg/L in drinking water) and followed for 16 months. At the end of the follow-up period, we determined inulin clearance, serum thiobarbituric acid reactive substances (TBARS), serum cholesterol, and urinary phosphate excretion. In addition, we performed immunohistochemical staining for p53 and for ED-1-positive cells (macrophages/monocytes), together with Western blotting of kidney tissue for NKCC2, aquaporin 2 (AQP2), urea transporter A1 (UT-A1) and Klotho protein. At baseline, the two groups were similar in terms of creatinine clearance, proteinuria, cholesterol, and TBARS. At the end of the follow-up period, NAC-treated rats presented greater inulin clearance and reduced proteinuria, as well as lower serum cholesterol, serum TBARS, and urinary phosphate excretion, in comparison with untreated rats. In addition, NAC-treated rats showed upregulated expression of NKCC2, AQP2, and UT-A1; elevated Klotho protein expression, low p53 expression, and few ED-1 positive cells. In conclusion, we attribute these beneficial effects of NAC (the significant improvements in inulin clearance and in the expression of NKCC2, AQP2, and UT-A1) to its ability to decrease oxidative stress, inhibit p53 expression, minimize kidney inflammation, and stimulate Klotho expression., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The aging process causes progressive deterioration in kidney structure and function. Aberrant generation of reactive oxygen species has been implicated in both age-related and ischemia-related tissue injury. Vitamin E (VE), one of the most powerful and effective exogenous antioxidants, prevents lipid peroxidation and protects against the effects of oxidative stress. The objective of this study was to determine the influence of age and VE on post-ischemic acute renal failure (ARF). Young adult, middle-aged and aged male Wistar rats were maintained on three different 30-day diets: Normal, VE absent and VE supplemented. On day 30, urinary protein and serum cholesterol and VE were measured. On day 31, rats were subjected to 60' clamping of the left renal artery plus right nephrectomy. Inulin clearance (InCl) was performed 48 h after renal ischemia. Malondialdehyde (MDA) was measured in the cortex of normal and 48-h post-ischemic kidneys. Urinary protein and serum cholesterol were higher in aged rats than in other rats. With aging, InCl decreased progressively. Vitamin E deficiency aggravated ARF. In middle-aged and aged rats, VE supplementation protected against ARF. In the absence of VE, MDA increased with age. In conclusion, our data suggest that ARF becomes more severe with age and that ischemia/reperfusion injury is exacerbated when antioxidant-scavenging ability of the kidney is impaired by VE deficiency. Supplementation with VE is essential for protecting aging kidneys against ischemic ARF.