Progressive losses of renal mass and the renal and hepatic disposition of administered inorganic mercury.

Abstract

The present study was designed to evaluate, in rats, the effect of progressive losses of renal mass, from a state where renal function is not compromised significantly to a state where the early stages of renal failure are detectable, on the disposition of administered inorganic mercury. As part of this evaluation, the intrarenal, hepatic, and hematological disposition of mercury and the urinary and fecal excretion of mercury were studied and characterized in control, uninephrectomized (NPX), and 75% nephrectomized (75% NPX) rats 1, 2, and 7 days after the intravenous injection of a nontoxic 0.5 mumol/kg dose of mercuric chloride. Clearance data showed that concentration of creatinine in the plasma was increased, whole animal glomerular filtration rate (GFR) was decreased, and the fractional excretion of sodium and potassium was increased in 75% NPX rats but not in NPX rats by the 12th day after surgery. These findings confirm that 75% nephrectomy in the rat causes changes that begin to compromise renal function significantly. Renal accumulation of mercury and the intrarenal distribution of mercury were significantly different between 75% NPX rats and NPX rats, presumably because of the differences in GFR and the renal clearance of mercury between the two groups of rats. Interestingly, the contents of mercury in the blood and liver were significantly greater in 75% NPX rats than in NPX or control rats. In addition, 75% NPX rats excreted significantly more mercury in the feces over the 7 days of study than did the other two groups of rats, indicating the hepato-biliary clearance of mercury was significantly greater in 75% NPX rats. Urinary excretion of mercury was also significantly greater in 75% NPX rats than in control rats or NPX rats. This enhanced urinary excretion of mercury may be related to polyuria that occurs in 75% NPX rats. In summary, the findings from the present study clearly indicate that the renal and hepatic handling of administered inorganic mercury in rats changes significantly when renal mass is reduced from about 50% to only about 25% of the original, total renal mass. Further studies are needed to better characterize the effects of 75% nephrectomy on both the disposition and the toxicity of inorganic mercury in renal and hepatic tissues and to determine the mechanisms responsible for the effects seen in this study.