Maleate effects on kidney peptidases and proteinuria of male and female rats. Histochemical and biochemical studies.
The effects of maleate on membrane-bound and lysosomal peptidases were studied histochemically in the kidney and biochemically in the kidney and the urine of male and female rats 6 h after the administration of two different doses of sodium maleate (150 and 300 mg/kg body weight). Additionally, the proteinuria of experimental animals was electrophoretically analysed to detect maleate-induced alterations in the urinary protein composition. The histochemistry of the brush-border peptidases (aminopeptidase A, gamma-glutamyltransferase) showed dose-dependent maleate effects in the late pars convoluta and the pars recta of the proximal tubule (blurring of the brush-border enzyme reaction pattern). The female animals were more severely affected by both maleate doses. After maleate treatment, enzyme-activity measurements in the kidney homogenate supernatant and urine indicated dose-dependent structural destruction of the proximal tubule, especially of brush-border membranes, and revealed an increase in enzyme excretion. Both the maleate-induced enzyme excretion and proteinuria were more pronouncedly increased in females than in males. Electrophoretic analysis of urinary proteins revealed alterations in the urinary-protein composition after maleate treatment, which favoured the excretion of proteins with a molecular weight higher than 20,000 daltons. Again, sex-related differences in the maleate effects were demonstrated. The results indicate that maleate causes alterations in the brush-border membranes and, especially at higher doses, results in cellular destruction selectively in the late proximal tubule of rat kidneys. Selectivity was also encountered in the maleate effects on urinary-protein composition, suggesting that the tubular alterations lead to an inhibition of the reabsorption of mainly high-molecular-weight proteins. Although the nature of the effects was independent of sex, it appears that females are less well protected against tubular damage caused by maleate.
Asan
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E
Kugler
P
P
D000626:Aminopeptidases / Q000378:metabolism*; D000818:Animals; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D043384:Glutamyl Aminopeptidase; D006651:Histocytochemistry; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007678:Kidney Glomerulus / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology; D008297:Male; D008298:Maleates / Q000008:administration & dosage / Q000494:pharmacology*; D011507:Proteinuria / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D008298:Maleates; C030272:maleic acid; D005723:gamma-Glutamyltransferase; D010450:Endopeptidases; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II