Effects of lead administration on developing rat kidney. I. Glutathione S-transferase isoenzymes.
The effects of acute and chronic exposure to lead on glutathione S-transferase (GST) isoforms were determined in developing kidney in the rat. The ontogeny of glutathione S-transferase isoforms was characterized as were the effects of depletion of dietary calcium on glutathione S-transferase isoform profiles in control and lead-treated rats. In the acute exposure experiments, rats of 14 and 50 days of age received three daily injections of lead acetate (114 mg/kg) and in the chronic exposure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutathione S-transferase isoform (Yb3); these increases were markedly exacerbated by dietary calcium depletion. In all lead paradigms, GST subunits Yb1 and Yp showed the largest increases--greater than 25-fold in rats fed a low-calcium diet. GST subunit Yb3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not increase in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-free water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels comparable to those in control rats fed lab chow.
Moser
R
R
Department of Pediatrics, Waisman Center, University of Wisconsin, Madison 53705.
Oberley
T D
TD
Daggett
D A
DA
Friedman
A L
AL
Johnson
J A
JA
Siegel
F L
FL
D000375:Aging / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005982:Glutathione Transferase / Q000187:drug effects*; D007527:Isoenzymes / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development*; D007674:Kidney Diseases / Q000139:chemically induced / Q000201:enzymology; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D008098:Litter Size / Q000187:drug effects; D046911:Macromolecular Substances; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; D007527:Isoenzymes; D046911:Macromolecular Substances; D007854:Lead; D005982:Glutathione Transferase; D002118:Calcium