RAT MODEL OF PERCHLOROETHYLENE-INDUCED RENAL DYSFUNCTIONS

To investigate whether perchloroethylene (PCE) can induce renal disturbances and to compare morphological alterations with functional data, two groups of 12 male and female Fischer-344 mature rats were treated daily with PCE (500 mg/kg body wt in corn oil, p.o.) for 4 weeks. Sex- and age-matched control groups received corn oil only. Weekly, the urinary excretion of albumin (Alb), α2μ-globulin (α2μ) and retinol-binding protein (RBP) was measured in 24-hr urine samples using immunoassays specific for rat proteins. N-acetylglucosaminidase (NAG) activity was measured by a colorimetric assay. Electrophoretic analysis of proteinuria included SDS-PAGE and isoelectric-focusing of Alb purified from serum and urine. Weekly histopathology comprised light and electron microscopy. In the male rat, a trend toward progressive albuminuria (up to 15 times the pair-fed controls) was oberved, together with transient increases in α2μ and NAG; RBP showed a twofold increase at the end of treatment. Histopathology failed to demonstrate glomerular changes, whereas it displayed α2μ accumulation and mild lesions in the S2 segment of proximal tubules. Thus, in the male rat, the selective damage to S2 was associated with "glomerular" proteinuria, the α2μ cortical content being closely correlated with albuminuria (n = 9, r = 0.92, P < 0.001). In the female rat, only minor, although statistically significant (P < 0.05), increases were recorded for Alb, whereas urinary α2μ reached up to four times the control values. As a whole, these findings suggest that PCE, like other hydrocarbons, selectively affects the tubular segment S2 in the rat. A competition with α2μ for tubular uptake could explain enhanced albuminuria. Owing to the species specificity of α2μ, caution should be exercised in extrapolating these findings to man. © 1992 Academic Press, Inc.