N-acetylcysteine attenuates the progression of chronic kidney disease / A N-acetilcisteína atenua a progressão da doença renal crônica

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

Oxidative stress biomarkers are increased in urine and plasma from renal chronic patients. Aldosterone (ALD) contributes to the kidney lesion in the remnant kidney model. Objectives: This studies was carried out to: 1- Determine the effect of antioxidant N-acetylcysteine (NAC) on kidney function and plasma aldosterone on animals with chronic renal failure (CRF); 2- Evaluate the effect of NAC on the CRF evolution, even when administered at a later stage; 3- Evaluate the effects of NAC associated with spironolactone (SPI). Material and Methods: Adult male Wistar rats were submitted to 5/6 nephrectomy (Nx). In study 1: Animals were treated or not with NAC (600 mg/l in drinking water), started 7 days after Nx. Clearance studies were performed on all rats at 21, 60 and 120 days after Nx. In study 2: 6 rats were treated with NAC initiated 60 days after Nx and studied 120 days after Nx. In study 3: rats were treated with Spi (1.5 g/Kg diet) associated or not to NAC, both initiated 7 days after Nx-treated rats and studied 60 days after Nx. In all experiments the following were measured: inulin clearance (GRF, ml/min/100g body weight); proteinuria (Uvpr, mg/24h); plasma aldosterone (ng/dl); urinary potassium/sodium ratio (UK/UNa); blood pressure (mmHg); urinary TBARS (nmoles/24h) and glomerulosclerosis index (%). Results: Mean daily NAC ingestion was similar in respective treated groups. A significant decrease in urinary TBARS (an index of lipid peroxidation) was observed in the NAC treated rats even when administered at a later stage. The main new finding of this study is that NAC administration to 5/6-Nx rats protects the glomerular filtration rate (GFR) significantly, with a mean inulin clearance of 0.45 (50% of the normal values), remaining stable 120 days following nephrectomy (0.51±0.03). Conversely, GFR fell progressively in untreated rats (0.16±0.03). In Nx+NAC rats, proteinuria, glomerulosclerosis index and blood pressure all decreased by day 120, and heart and adrenal hypertrophy were attenuated. These beneficial effects were associated with a significant reduction in plasma aldosterone and urinary sodium/potassium (UK/UNa) ratio (indirect marker of aldosterone tubular action) and were observed even when NAC was administered later (60 days after Nx). Mortality was 33% in the Nx 120 group, 25% in the Nx120+NAC group and 14.3% in the Nx120 (Nx60+60NAC). In study 3: Spironolactone isolatedly decreased proteinuria in the Nx animals, however when associated with NAC it caused more protection of GFR (Nx60+NAC+Spi = 0.59±0.04 vs Nx60+NAC = 0.47 ± 0.05, p <0.001) and lower blood pressure (136±2 mmHg) than in the animals treated only with NAC (154±2 mmHg). The combination of Spi and NAC lowered blood pressure and improve GFR protection. Conclusion: 1. In the remnant kidney model, NAC has a protective effect attributable to decreased plasma aldosterone and lower of lipid peroxidation indicative of thiobarbituric acid reactive substances (TBARS) lower levels, even in the later stages. 2. Combination of NAC and Spi showed an extra beneficial effect over glomerular filtration, and a higher decrease of blood pressure.

ASSUNTO(S)

aldosterona wistar rats inulina spironolactone acetylcysteine thiobarbituric acid reactive inulin ratos wistar testes de função renal chronic kidney failure lipid peroxidation substâncias reativas com ácido tiobarbitúrico aldosterone insuficiência renal crônica peroxidação de lipídeos acetilcisteína kidney function renal espironolactona.

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