Partial protection by chlorpromazine in mercuric chloride-induced acute renal failure in rats

Previous studies have demonstrated that the anesthetic amine, chlorpromazine hydrochloride (CPZ), prevents cell necrosis in experimentally induced ischemic liver and heart disease and decreases the extent of galactosamine-induced cell death in the liver. The present model was designed to determine whether CPZ exerts a similar beneficial effect in kidney in a nephrotoxic model of acute renal failure in rats induced by the administration of mercuric chloride (2 mg/kg of body weight). The functional and structural changes in the kidney were evaluated and quantitated in animals pretreated with CPZ (40 mg/kg of body weight) or saline and then subjected to nephrotoxic injury. Compared to controls, the glomerular filtration rate was significantly lower (p less than 0.001) in saline- and CPZ-pretreated rats receiving mercuric chloride. Twenty-four hours after mercuric chloride administration the glomerular filtration rate was 446 +/- 38 microl/minute/gm of kidney weight, the fractional sodium excretion was 0.4 +/- 0.2%, and the urinary osmolality was 1440 +/- 193 mOsmoles/kg of H2O in the CPZ-treated animals compared to 26 +/- 18 microl/minute/gm of kidney weight (p less than 0.001), 10.1 +/- 9.8% (p less than 0.025), and 353 +/- 28 mOsmoles/kg of H2O (p less than 0.005), respectively, in the animals receiving mercuric chloride alone. The percentage of proximal tubule cell necrosis was 26.5 +/- 8.9% in the CPZ-pretreated group compared to 88.1 +/- 3.6% in the untreated group (p less than 0.001). Metabolic cage studies were performed to follow the time course of this model for 48, 72, and 96 hours after mercury injection. The serum creatinine values and fractional sodium excretions were significantly less in animals receiving CPZ compared to the untreated group at all time intervals examined. The serum urea nitrogen concentration and glomerular filtration rate were similar for the two groups after 48 hours, but the serum urea nitrogen level was significantly lower and the glomerular filtration rate higher after 72 and 96 hours in the animals pretreated with CPZ. In agreement with these findings were observations that animals pretreated with CPZ had significantly fewer necrotic cells 48 and 72 hours after mercury administration, and tubular regeneration appeared to be markedly accelerated. These results suggest that pretreatment with CPZ markedly lessens the degree of structural and functional impairment seen in mercuric chloride-induced acute renal failure in rats and increases the rate of recovery.