Relevance of enzyme evaluations in 24h urine to rat kidney injury caused by i.v. cephaloridine injection.

Abstract

Male rats were housed singly in metabolic cages, injected i.v. with cephaloridine, 24 h urine samples collected successively; then the rats were killed for obtaining the kidneys of corresponding animals. The concentrations of protein, aminopeptidase (AP), alkaline phosphatase (aPP), lactic dehydrogenase (LDH), and aldolase (ALD) were determined in urine and the percentages of injured proximal tubules counted in sections stained for aPP. The results from individual animals were: (1) After placing animals singly in metabolic cages large but not systematic changes of urinary enzyme concentrations occurred. After 6-10 days the enzymes reached steady state levels. (2) After a single injection of cephaloridine a dose dependent injury of proximal tubules was observed, the urinary LDH content correlating best with the tubular injury (r greater than 0.93) and giving up to 1,000 fold increases above normal values. (3) A circadian rhythm of the susceptibility of rat kidney for cephaloridine was observed, the smallest response was seen when the animals were injected at 7 a.m. and the largest after injection at 7 p.m. (4) In subacute toxicity studies urinary LDH was increased on day 2 above the extent after a single dose, but declined on day 3 to reach normal levels after 8 to 10 days (time of sacrifice). The kidneys revealed practically normal histology. The other enzymes studied had also returned to normal values. This indicates some adaptation mechanism.