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Background.N-Acetylcysteine has been shown to protect against contrast nephropathy, although the mechanisms underlying such an effect are unclear. Surprisingly, studies have shown that post-radiocontrast renal function actually improves in chronic renal failure patients receiving N-acetylcysteine. However, there have been no studies investigating the cause of this improvement.Methods. In a double-blind, placebo-controlled study, 24 patients (aged 65±2 years) suffering from stable mild-to-moderate renal insufficiency and undergoing elective coronary angiography were randomized to receive either placebo or N-acetylcysteine. All received similar hydration. Renal function parameters were assessed 48 h before and 48 h after radiocontrast administration. Urinary 15-isoprostane F2t, a specific marker of oxidative stress, was measured immediately before and after the procedure. Expression of urinary α-glutathione S-transferase protein, a specific proximal tubular injury marker, was assessed after the procedure.Results. Comparing creatinine clearance values before and after angiography, a significant increase was seen in N-acetylcysteine patients (44.7±4.2 vs 57.2±6.3 ml/min/1.73 m2; P = 0.02), whereas placebo patients presented no change (46.6±5.0 vs 46.9±4.3 ml/min/1.73 m2; P = 0.90). After radiocontrast, urinary 15-isoprostane F2t levels in placebo patients increased significantly over baseline values (2.9±0.7 vs 10.3±2.1 ng/mg creatinine; P = 0.007), whereas urinary 15-isoprostane F2t levels in N-acetylcysteine patients remained basically unchanged (3.5±0.5 vs 4.1±0.9 ng/mg creatinine; P = 0.63). Furthermore, N-acetylcysteine treatment led to lower levels of α-glutathione S-transferase than did placebo treatment (0.8±0.2 vs 2.4±0.7 µg/g; P = 0.046).Conclusions. In chronic renal failure patients, the improvement in renal function induced by post-radiocontrast administration of N-acetylcysteine is strongly associated with suppression of oxidant stress-mediated proximal tubular injury. [ABSTRACT FROM AUTHOR]

Background. Obstructive nephropathy decreases renal blood flow (RBF) and glomerular filtration rate (GFR), causing tubular abnormalities, such as urinary concentrating defect, as well as increasing oxidative stress. This study aimed to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on the protein expression of aquaporin 2 (AQP2) and endothelial nitric oxide synthase (eNOS), after the relief of bilateral ureteral obstruction (BUO). Methods. Adult male Wistar rats were divided into four groups: sham (sham operated); sham operated + 440 mg/kg body weight (BW) of NAC daily in drinking water, started 2 days before and maintained until 48 h after the surgery; BUO (24-h BUO only); BUO + NAC-pre (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started 2 days before BUO); and BUO + NAC-post (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started on the day of BUO relief). Experiments were conducted 48 h after BUO relief. Results. Serum levels of thiobarbituric reactive substances, which are markers of lipid peroxidation, were significantly lower in NAC-treated rats than in the BUO group rats. The administration of NAC provided significant protection against post-BUO GFR drops and reductions in RBF. Renal cortices and BUO rats presented decreased eNOS protein expression of eNOS in the renal cortex of BUO group rats, whereas it was partially recovered in BUO + NAC-pre group rats. Urine osmolality was significantly lower in BUO rats than in sham group rats or NAC-treated rats, the last also presenting less interstitial fibrosis. Post-BUO downregulation of AQP2 protein expression was averted in the BUO + NAC-pre group rats. Conclusions. This study demonstrates that NAC administration ameliorates the renal function impairment observed 48 h after the relief of 24-h BUO. Oxidative stress is important for the suppression of GFR, RBF, tissue AQP2 and eNOS in the polyuric phase after the release of BUO. [ABSTRACT FROM AUTHOR]