EFFECTS OF LEAD ADMINISTRATION ON DEVELOPING RAT-KIDNEY .2. FUNCTIONAL, MORPHOLOGIC, AND IMMUNOHISTOCHEMICAL STUDIES

The effects of chronic lead administration on renal function and cytoa rchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were gi ven 250 ppm lead acetate in drinking water from conception until weani ng and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age, Light and electron mi croscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, afte r 7 weeks of treatment, interstitial fibrosis, characteristic intranuc lear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed si gnificantly lower body weights and creatinine clearances than age-matc hed control animals, Immunohistochemical studies of glutathione transf erase subunits in control rats showed unique isoform localization in e ach segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb-1, and Yp GST subunits in pro ximal tubules, No increases in the antioxidant enzymes copper-zinc sup eroxide dismutase, catalase, and glutathione peroxidase were found in lead-treated rats, but there was a diffuse lead-related increase in im munoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cel l types and show that these increases preceded irreversible renal dama ge. (C) 1995 Academic Press, Inc.