K. Buyukafsar et al., Effect of trapidil, an antiplatelet and vasodilator agent on gentamicin-induced nephrotoxicity in rats, PHARMAC RES, 44(4), 2001, pp. 321-328
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.