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In order to establish sensitive methods of detecting minor renal damage, changes of enzymes, protein, tubular cell counts, and creatinine in the urine were investigated in rats to which nephrotoxic chemicals had been administered. Daily administration of p-aminophenol (PAP) dose-dependently increased urinary excretions of lactate dehydrogenase (LDH) and its isoenzymes (LDH5 = LDH4 greater than LDH3 greater than LDH2 = LDH1), aspartate aminotransferase (GOT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP), leucine aminopeptidase (LAP), lysozyme (LZM), N-acetyl-beta-D-glucosaminidase (NAG) and acid protease together with increased counts of tubular cells in the urine. Tubular cell counts, LDH and GOT were more sensitive indicators in the PAP tubulonephritis. Single i.v. injection of puromycin aminonucleoside (PM) dose-dependently increased urinary excretions of LDH and its isoenzymes (LDH1 = LDH5 greater than LDH2 = LDH4 greater than LDH3), GOT, NAG, acid protease and protein but degree of the increases in these enzymes was lower than those in the rats treated with PAP. PM increased excretions of high molecular weight proteins but did not increase ALP, gamma-GTP, LAP, LZM and tubular cells excretions. Single i.v. injection of hexadimethrine increased urinary excretion of LDH and its isoenzymes (LDH1 = LDH5 greater than LDH2 greater than LDH3 = LDH4), GOT, LZM, NAG and acid protease together with increased counts of tubular cells in the urine but did not increase ALP, gamma-GTP and LAP excretions. It is concluded that tubular cell counts, LDH isoenzymes and battery of these enzymes in urine are useful markers for detecting the severity and the site of renal damage in addition that urinary protein is a useful marker for detecting glomerular damage.

journal of toxicological sciences

Urinalysis for detection of chemically induced renal damage. (2). Changes in urinary excretions of enzymes and various components caused by p-aminophenol, puromycin aminonucleoside and hexadimethrine.