PYRIDINE INDUCTION OF SPRAGUE-DAWLEY RAT RENAL CYTOCHROME P4502E1 - IMMUNOHISTOCHEMICAL LOCALIZATION AND QUANTITATION

Previous research has shown that i.p. injection of rats with pyridine results in a significant increase in immunoreactive renal cytochrome P 4502E1 (alcohol-inducible form) in a dose- and time-dependent manner. However, the cellular location of renal P4502E1 in rats was not report ed. Thus, it was not known whether the pyridine-induced increase in re nal P4502E1 resulted from increased production of the enzyme in cells which normally express P4502E1 or from de novo expression in cells nor mally devoid of the protein. To address these questions, rats were inj ected i.p. with either 200 mg pyridine/kg body wt./dy for 1, 2, 3, or 4 days (n = 2/group) or injected once with an equal volume of sterile, pyrogen-free saline (control group; n = 2). Kidney tissue samples fro m saline- and pyridine-exposed rats were processed by light microscopy and were immunochemically stained to detect rat cytochrome P4502E1. M ost of the immunoreactive P4502E1 was located within renal cortical ep ithelial cells lining proximal and distal tubules pf the cortex with l esser - but consistent - amounts present in tubular epithelial cells w ithin the inner and outer medulla. Pyridine exposure resulted in a 2-3 -fold increase in P4502E1 immunoreactivity in proximal cortical tubule s surrounding glomeruli and cortical blood vessels. The results of thi s study demonstrate a cell-specific distribution of cytochrome P4502E1 within the rat kidney and indicate that pyridine exposure results in a selective induction of immunoreactive P4502E1 in tubule epithelial c ells which constitutively express this enzyme. The results of this stu dy provide a morphologic basis for interpreting cell-specific nephroto xicity due to xenobiotics that are biotransformed to toxic metabolites by renal P4502E1.