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In order to establish sensitive methods of detecting minor renal damage, changes of enzymes, tubular cell counts, and creatinine in the urine were investigated in rats that had been given nephrotoxic chemicals. Daily administration of mercuric chloride (HgCl2) dose-dependently increased urinary excretions of lactate dehydrogenase (LDH), aspartate aminotransferase (GOT), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), lysozyme (LZM), N-acetyl-beta-D-glucosaminidase (NAG), and acid protease together with increased counts of tubular cells in the urine. The increase in tubular cell counts and the change in urinary LDH isoenzyme profile preceded the changes in the other enzymes. Daily administration of gentamicin (GM) increased urinary excretions of LDH, GOT, LZM, NAG, acid protease and tubular cell counts in a dose-dependent manner, but did not increase gamma-glutamyl transpeptidase (gamma-GTP) and ALP excretions. The urinary isoenzyme profiles of LDH in rats treated with GM were different from those with HgCl2. The increase in acid protease excretion outlasted those in LDH and GOT in the high dose group. It was concluded that the severity of renal damage can be readily detected by periodic determinations of the following urinary parameters: tubular cell counts, LDH isoenzyme, acid protease, LZM and NAG, in addition to either LDH or GOT and one of the enzymes ALP, LAP or gamma-GTP. Furthermore, the site of renal damage can be presumed from these results.

journal of toxicological sciences

Urinalysis for detection of chemically induced renal damage. (1). Changes in urinary excretions of enzymes and various components caused by mercuric chloride and gentamicin.