Nephrotoxic effects on offspring of rats chronically treated with mercuric chloride

Repeated subcutaneous injections of HgCl₂ at a dose of either 4.0 or 2.0 mg/kg produced toxic effects in rats when administered during the last 9 days of gestation. Females exhibited diarrhea, anorexia and weight loss of varying severity. Maternal renal function was monitored by urinalysis and was shown to be impaired during the early days of treatment but returned to normal later. Histological evaluation of adult kidneys after 2 days of treatment demonstrated the nephrotoxic effects of HgCl₂; however, after 9 or 19 HgCl₂ injections, kidneys showed little evidence of damage. The adult kidneys were apparently capable of repair and regeneration in spite of continued administration of the nephrotoxic agent. Evidence of the regenerative process was found in tubules lined with densely packed, flattened cuboidal epithelial cells. These cells did not stain for mitochondria, and were probably not functionally mature. As indicated by the normal urinalysis results, these immature tubular cells did not result in a functional deficit, demonstrating the great functional reserve of the kidney.

Administration of HgCl₂ to pregnant rats was not overtly toxic to their developing offspring, perhaps because of the time of administration. Pup birth weight among HgCl₂-exposed litters, however, was significantly lower than that of control litters. Nephrotoxic effects were not identifiable in pups at birth or 12 days later, though the presence of mercury was confirmed in fetal kidneys after 2 days of exposure. Effects could have been too subtle to detect by light microscopy, or nephrotoxic injury may have occurred but been masked by subsequent renal development. If the latter is true, it would appear that the perinatal rat kidney, by the very nature of its development, is resistent to HgCl₂-induced injury and thus may not be as sensitive to mercury intoxication as its adult counterpart or as other developing tissues.