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 9 glomerular filtration rate (GFR) was assessed by ^99mTechnetium diethylene triaminepenta-acetic 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±10.25 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.