metallothionein and Oliguria

It has been demonstrated that the sensitivity to HgCl2 nephrotoxicity increases with maturity in the rat, and that neonates are largely unaffected by a dose of 5 mg/kg. In the present study, immature rat pups were exposed to higher doses of HgCl2 to determine whether this effect was attributable to a quantitative or qualitative difference in the renal sensitivity to HgCl2. Sprague-Dawley rats were injected with a single dose of 5, 7.5, 10, 12.5, 20, or 30 mg/kg on Postnatal Day 1; 5, 7.5, 10, 12.5, 15, or 20 mg/kg on Day 8; or 6.25, 7.5, 10, or 12.5 mg/kg on Day 15. Renal function was evaluated at 24, 48, and 120 hr after treatment by measuring urine volume, osmolality, urinary pH, and chloride content, the ability to concentrate urine during water deprivation, and the presence of protein, glucose, or hemoglobin in urine. Animals were then killed and their kidneys weighed. A dose of 20 mg/kg was needed to induce mortality in pups treated at 1 day of age, and 15 mg/kg was needed in pups treated at 8 days of age. In contrast, the 6.25-mg/kg dose given to 15-day-old pups produced some mortality, and all rats given higher doses at 15 days of age died within 2 days. There was marked oliguria or anuria in the rats that died. Kidney weight was increased in a dose-related fashion at all ages. In those animals not rendered oliguric by the treatment, urine volume increased and the ability to secrete a more concentrated urine during water deprivation decreased. Urinary pH was decreased in a dose-related manner. Urinary chloride excretion was temporarily decreased after HgCl2 treatment on Day 1 , but was increased thereafter. Proteinuria, glucosuria, and hematuria were detected in the treated rats, again increasing in frequency and severity with age and dose.

Topics: Age Factors; Animals; Animals, Newborn; Chlorides; Dose-Response Relationship, Drug; Female; Kidney; Liver; Mercuric Chloride; Mercury; Metallothionein; Oliguria; Osmolar Concentration; Pregnancy; Rats; Rats, Inbred Strains