Effect of trapidil, an antiplatelet and vasodilator agent on gentamicin-induced nephrotoxicity in rats.
This study was carried out to evaluate the effect of trapidil, an antiplatelet and vasodilator drug, on the nephrotoxicity by an aminoglycoside, gentamicin, in rats. Forty female Wistar rats were divided into six different groups. One group served as a control group and the other groups were treated as follows: gentamicin (50 mg kg(-1) twice daily)-treated, gentamicin plus trapidil (4 or 20 mg kg(-1) daily)-treated and only trapidil-treated (4 or 20 mg kg(-1) daily) groups. Serum urea, creatinine and nitrite/nitrate levels were measured. Moreover, histopathological as well as electron microscopic examinations were performed. At a lower dose (4 mg kg(-1)) trapidil did not prevent the development of renal tubular damage by gentamicin. However, a higher dose of trapidil (20 mg kg(-1)) inhibited the ability of gentamicin to increase the levels of creatinine and urea. Furthermore, both light and electron microscopic evaluation confirmed the nephroprotective effect of the higher dose of trapidil. The level of the stable nitric oxide (NO) metabolite, nitrite, was also increased by trapidil. In conclusion, trapidil at a higher dose may protect against gentamicin nephrotoxicity. The mechanism underlying trapidil nephroprotection is not known, but may result from the antagonism of platelet-derived growth factor (PDGF), vasodilatation, inhibition of trombosit aggregation, and/or NO release.
Büyükafşar
K
K
Department of Pharmacology, Medical Faculty, Mersin University, Turkey. kbuyukafsar@mersin.edu.tr
Yazar
A
A
Düşmez
D
D
Oztürk
H
H
Polat
G
G
Levent
A
A
D000818:Animals; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005839:Gentamicins; D007668:Kidney / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000648:ultrastructure; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000819:agonists* / Q000097:blood; D009573:Nitrites / Q000819:agonists / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014192:Trapidil / Q000494:pharmacology*; D014508:Urea / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology*
D005839:Gentamicins; D009566:Nitrates; D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D014508:Urea; D003404:Creatinine; D014192:Trapidil