PENTOXIFYLLINE REDUCES NEPHROTOXICITY ASSOCIATED WITH CYCLOSPORINE INTHE RAT BY ITS RHEOLOGICAL PROPERTIES

Background. The goals of this study were to evaluate whether administr ation of pentoxifylline (POF) reduces the nephrotoxicity associated wi th cyclosporine (CsA) in the rat, and whether the effect of POF is rel ated to its rheological properties. Methods. Mean arterial pressure wa s measured by an intrarterial catheter. Glomerular filtration rate and renal plasma flow were determined by measuring inulin and para-aminoh ippurate clearances, after double-blind coadministration for 10 days o f CsA (25 mg/kg/day) with either vehicle or POF (45 mg/kg every 12 hr) . These results were compared with those obtained in control rats. Blo od viscosity and erythrocyte deformability were also evaluated after t reatment using a cone plate viscometer and a filtration method, respec tively. Results No changes were observed in mean arterial pressure in both groups compared with controls, Glomerular filtration rate was sig nificantly lower in CsA-treated rats (0.3+/-0.1 ml/min/100 g) than in control animals (0.6+/-0.1 ml/min/100 g, P<0.02). The coadministration of CsA with POF normalized the glomerular filtration rate (0.6+/-0.1 ml/min/100 g). A parallel decrease in renal plasma flow was observed i n CsA-treated rats compared with controls (CsA+vehicle: 1.5+/-0.2 vs. control: 2.2+/-0.1 ml/min/100 g, P<0.02), this effect completely rever sed by cotreatment with POF (3.1+/-0.2 ml/min/100 g). Blood viscosity was significantly higher in CsA-treated rats than in the control group (CsA+vehicle: 5.6+/-0.7 vs. control: 5.0+/-0.4 m.Pa.s, P<0.05). This effect was associated with a lower erythrocyte deformability (CsA+vehi cle: 1.2+/-0.2 vs. control: 1.5+/-0.3 ml/min, P<0.05). These rheologic al abnormalities were normalized by coadministration with POF (blood v iscosity: 4.9+/-0.7 m.Pa.s and erythrocyte deformability: 1.9+/-0.4 ml /min, P<0.05). Conclusions. Our results show that administration of PO F prevents the nephrotoxicity associated with CsA. This beneficial eff ect could be related to its rheological properties.