Toxicity of mercuric chloride to the developing rat kidney. III. Distribution and elimination of mercury during postnatal maturation.
Mercuric chloride is a potent nephrotoxicant in the adult rat, but has little effect on newborns. Nephrotoxicity increases with postnatal maturation. This study assesses the changes in tissue distribution and excretion of Hg during postnatal development. Sprague-Dawley rats were injected sc with 5 mg/kg 203HgCl2 on postnatal Day 1, 8, 15, 22, or 29. Hg concentration was measured in the whole body, renal cortex, medulla and papilla, liver, and subcellular fractions of liver and kidney. Binding to cytosolic metallothionein was assessed. Whole-body elimination of Hg was slow at the three younger age groups, as only 20% of the initial load was eliminated by 5 days after injection. Excretion was much more rapid in the two older groups, which eliminated about half of the initial load within 5 days. Concentration of Hg was highest in renal cortex (the principal site of Hg toxicity), and there was an age-related increase in cortical Hg concentration. This may explain the increased toxicity of Hg with age. There was an age-related decrease in hepatic Hg concentration. The high levels of metallothionein present in perinatal rat liver may protect the renal cortex from receiving a toxic dose of Hg; however, the increased concentration of hepatic Hg in newborns is insufficient to account for all of the cortical decrease. It is probable that Hg was distributed to other tissues. In liver and kidney cells of neonates, Hg concentration was highest in the cytosol, decreasing in an age-related manner. This was accompanied by an age-related increase of Hg in the nuclear/mitochondrial fraction. Hg in the cytosol was largely bound to metallothionein, although there were substantial amounts associated with very low-molecular-weight molecules and high-molecular-weight proteins. There are significant maturational changes in the organ, cellular and subcellular distribution of Hg in the rat during the first 4 weeks after birth. These probably explain the increasing sensitivity with maturity to Hg nephrotoxicity.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001822:Body Burden; D003600:Cytosol / Q000032:analysis; D005260:Female; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D008627:Mercuric Chloride