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 antiplate let and vasodilator drug, on the nephrotoxicity by an aminoglycoside, genta micin, in rats. Forty female Wistar rats were divided into six different gr oups. 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 lev els were measured. Moreover, histopathological as well as electron microsco pic 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 gentami cin to increase the levels of creatinine and urea. Furthermore, both light and electron microscopic evaluation confirmed the nephroprotective effect o f the higher dose of trapidil. The level of the stable nitric oxide (NO) me tabolite, nitrite, was also increased by trapidil. In conclusion, trapidil at a higher dose may protect against gentamicin nephrotoxicity. The mechani sm underlying trapidil nephroprotection is not known, but may result from t he antagonism of platelet-derived growth factor (PDGF), vasodilatation, inh ibition of trombosit aggregation, and/or NO release. (C) 2001 Academic Pres s.