[Study on gamma-GTP activity in urine and renal tissue of drug-induced nephrotoxicity in rats].
We investigated changes of urinary and renal gamma-glutamyl transpeptidase (gamma-GPT) activities in rat with renal damages caused by nephrotoxic agents in order to clarify the onset and the course of these nephrotoxicities. Cisplatin (CDDP) which is an antitumor agent, cephaloridine (CER) which is the first-generation cephem, and gentamicin (GM) which is an aminoglycoside were employed as tested nephrotoxic agents. We administered three fourth of LD50 of each agent to male Fischer 344 rats, intra-peritoneally. And the time-course changes of serum creatinine (s-Cr) value, creatinine clearance (Ccr) and urinary gamma-GTP activity were observed after administration of each agent. Finally, we measured renal gamma-GTP activities and observed pathological changes of the kidneys. The elevation of s-cr values and the reduction of Ccr appeared 3 days and 12 hours after the administration of CDDP and CER, respectively. And the peak appeared 7 days and 3 days after the administration of CDDP and CER, respectively. Increase of urinary gamma-GTP activities occurred earlier than the peak of s-cr value and Ccr in each group and as early 12 hours after the administration. In CER groups, the peak of urinary gamma-GTP activities was observed within 12 hours after the administration. And the peak of urinary gamma-GTP activities was observed at 24 hours and in 3 days after the administration of GM and CDDP, respectively. In addition, renal gamma-GTP activities reduced around 40% of those of control.(ABSTRACT TRUNCATED AT 250 WORDS)
Furuta
N
N
Department of Urology, Jikei University, School of Medicine.
Nakada
J
J
D000818:Animals; D002509:Cephaloridine / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D005839:Gentamicins / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000378:metabolism* / Q000652:urine
D005839:Gentamicins; D005723:gamma-Glutamyltransferase; D002509:Cephaloridine; D002945:Cisplatin