Toxicity of mercuric chloride to the developing rat kidney I. Postnatal ontogeny of renal sensitivity

Abstract

Although the sensitivity of the adult rat kidney to mercuric chloride has been widely reported, the degree to which this toxicant affects the developing kidney is unknown. Therefore, this study examined the effects of HgCl 2 on renal function during postnatal maturation. Sprague-Dawley rats were treated with a single sc injection of 5 mg/kg HgCl 2 on Day 1, 8, 15, 22, or 29 after birth. The effects on renal function, histology, and morphology were assessed 24, 48, and 120 hr after each treatment. Measurements of renal function included urine volume, osmolality, the ability to concentrate urine during water deprivation, urinary pH, chloride and protein content, tests for glucosuria, hematuria, and various serum chemistry parameters. Rats were killed and their kidneys processed and examined by light microscopy. The renal sensitivity to HgCl 2 increased throughout maturation for every parameter measured. No pups treated with HgCl 2 on Day 1 died, but mortality increased to almost 20% in rats treated 22 and 29 days after birth. Body weight was unaffected in Day 1 animals, but was decreased at 120 hr post-treatment in three of the other four age groups. Kidney weights were unaffected in 1- and 8-day olds, but were increased by 10 to 55% in rats that were 15, 22, and 29 days old. Urine volume was increased 48 to 72 hr following treatment at all ages. The ability to concentrate urine in response to water deprivation was compromised in all animals with the exception of those treated on Day 1, and was decreased to the greatest extent in 29-day-olds. Urinary chloride concentration was decreased in Day-22 animals at 24 and 48 hr, and in Day-29 rats at all times observed after injection. Urinary pH was more acidic in treated suckling pups, and more basic in treated pups after weaning on Day 22. Urinary protein content was increased after exposure in all but the pups treated on Day 1. Serum creatinine was increased at 120 hr after injection in Day-8 rats, and 24 and 48 hr after injection in older rats. Glucosuria and hematuria occurred with increasing frequency as the pups matured. Histological evaluation revealed some cortical tubular dilatation in rats treated on Day 1 or Day 8; there was tubular necrosis in older rats. For all parameters observed, the neonatal kidney was largely insensitive to HgCl 2 toxicity; however, a trend toward increased sensitivity with increasing age was demonstrated.