EFFECTS OF LEAD ON RAT-KIDNEY AND LIVER - GST EXPRESSION AND OXIDATIVE STRESS

The effect of acute exposure to lead acetate on the expression of glut athione S-transferase (GST) subunits and the levels of reduced and oxi dized glutathione (GSH) and malondialdehyde (MDA) in rat kidney and li ver was determined. The purpose of this study was to determine if GSH depletion and/or oxidative stress were responsible for changes in the expression of some or all GSTs that followed lead exposure. In kidney, all GST subunits increased following injection of lead. The level of kidney GSH was not changed at either 0.5 or 1 h after lead exposure, b ut increased 3, 6, 12 and 24 h after a single injection of lead. MDA l evels (a marker of lipid peroxidation) did not change in kidney follow ing lead injection. Immunohistochemical markers of oxidative stress an d nitric oxide production were also unchanged by lead administration. Therefore, we conclude that the increases in GST levels in kidney foll owing lead exposure were not dependent on oxidative stress. In liver, lead injection caused GSH depletion (61% of control 12 h after lead tr eatment) and increased MDA production (2.5-fold increase 6 h after lea d exposure), while GSTA1, GSTA2, GSTM1 and GSTM2 did not increase. Ana lysis of the effects of lead on GST mRNA and GST cellular localization were performed by Northern blot and immunohistochemical techniques. I mmunoperoxidase light microscopy and immunogold electron microscopy re vealed that the increase in kidney GSTM1 and GSTP1 occurred in nuclei: cytoplasm and microvilli of proximal tubules, Northern blot analysis of GSTA2 and GSTP1 mRNAs showed that their increase following lead exp osure was inhibited by actinomycin D, suggesting transcriptional induc tion. This study demonstrates that acute lead exposure causes dramatic changes in the subcellular distribution and expression of rat kidney GSTs, and that these changes are not a result of oxidative stress. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.