N-acetylcysteine attenuates the progression of chronic renal failure.
BACKGROUND
Lipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure.


METHODS
Adult male Wistar rats were submitted to 5/6 nephrectomy or laparotomy (sham-operated) and received NAC (600 mg/L in drinking water, initiated on postoperative day 7 or 60), spironolactone (1.5 g/kg of diet initiated on postoperative day 7), the NAC-spironolactone combination or no treatment. Clearance studies were performed on postoperative days 21, 60, and 120.


RESULTS
Mean daily NAC and spironolactone ingestion was comparable among the treated groups. Mean weight gain was higher in NAC-treated rats than in untreated rats. A significant decrease in urinary thiobarbituric acid reactive substances (TBARS) concentrations, a lipid peroxidation marker, was observed in NAC-treated rats. By day 120, glomerular filtration rate (GFR), which dropped dramatically in untreated rats, was stable (albeit below normal) in NAC-treated rats, which also presented lower proteinuria, glomerulosclerosis index, and blood pressure, together with attenuated cardiac and adrenal hypertrophy. These beneficial effects, observed even when NAC was initiated on postnephrectomy day 60, were accompanied by a significant reduction in plasma aldosterone and urinary potassium sodium [corrected] ratio. The NAC-spironolactone combination lowered blood pressure and improved GFR protection.


CONCLUSIONS
The NAC-spironolactone combination improves renal function more than does NAC alone. In the remnant kidney model, early or late NAC administration has a protective effect attributable to decreased plasma aldosterone and lower levels of lipid peroxidation.
Shimizu
Maria Heloisa Massola
MH
Nephrology Department, University of São Paulo School of Medicine, Brazil.
Coimbra
Terezila Machado
TM
de Araujo
Magali
M
Menezes
Luis Fernando
LF
Seguro
Antonio Carlos
AC
D000111:Acetylcysteine / Q000494:pharmacology*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology
D000975:Antioxidants; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D000111:Acetylcysteine