N-Acetylcysteine ameliorates lithium-induced renal failure in rats.
BACKGROUND
Prolonged lithium treatment may induce progressive deterioration of renal function in humans and experimental animals. N-Acetylcysteine (NAC) has been shown to be effective in the prevention of hypoperfusion and toxin-induced renal failure, but its effect on lithium nephrotoxicity has not been evaluated yet. The purpose of this study was to examine a possible renoprotective effect of NAC against lithium-induced renal failure in a rat model.


METHODS
Moderate renal failure was induced in 40 Sprague-Dawley rats using a 5 week protocol including 3 weeks of lithium chloride administration in the drinking water. The animals were divided randomly into two equal groups receiving either 10 mg/kg NAC or saline by two daily intraperitoneal injections. In week 6, the glomerular filtration rate (GFR) was assessed by 99mTechnetium diethylene triaminepentaacetic acid, and serum creatinine, blood urea nitrogen (BUN) and 24 h urinary protein and osmolarity were measured. Kidneys were excised for pathological evaluation.


RESULTS
At the end of the lithium protocol, the GFR was significantly higher in the NAC-treated group compared with the control group, 0.92+/-0.35 vs 0.56+/-0.25 ml/min/100 g, respectively, P = 0.002. Serum creatinine and BUN were also significantly lower in the NAC-treated group 1.009+/-0.107 vs 1.143+/-0.118 mg/dl, P = 0.001, and 83.9+/-6.8 vs 88.95+/-7.1 mg/dl, P = 0.28, respectively. The percentages of tubular necrosis and tubular lumen obstruction, evaluated by light microscopy, were significantly lower in the NAC-treated group, P = 0.002 and P = 0.007, respectively.


CONCLUSIONS
NAC treatment has a renoprotective effect against lithium-induced renal failure in a rat model.
Efrati
Shai
S
Department of Medicine A, Assaf Harofeh Medical Center, Zerifin, Israel. efratishai@013.net.il
Averbukh
Michael
M
Berman
Sylvia
S
Feldman
Leonid
L
Dishy
Victor
V
Kachko
Leonid
L
Weissgarten
Joshua
J
Golik
Ahuva
A
Averbukh
Zhan
Z
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007677:Kidney Function Tests; D008094:Lithium; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D051437:Renal Insufficiency / Q000473:pathology* / Q000517:prevention & control*; D012680:Sensitivity and Specificity
D008094:Lithium; D000111:Acetylcysteine