BENEFICIAL-EFFECTS OF PENTOXIFYLLINE ON CYCLOSPORINE-INDUCED NEPHROTOXICITY

1. Hypertension and renal failure are the two most common and severe c omplications due to cyclosporine A (CsA) therapy after transplantation . To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the toxic effects of CsA, three groups of rats were studie d. 2. The first group of rats (n = 11) received daily injections of Cs A (15 mg/kg, i.m.) and PTX (45 mg/kg, i.p., b.i.d.), the second group of rats (n = 11) was treated with CsA only and the third group of rats (n = 11) served as the control group (vehicle treatment). 3. Whole bl ood CsA levels were similar in CsA + PTX and CsA alone groups, Althoug h CsA treatment significantly increased mean arterial blood pressure ( 110.00 +/- 2.48 mmHg; P < 0.01), there was no significant increase in the PTX co-treated group (104.09 +/- 2.96 mmHg) compared with initial values. In both the CsA alone and CsA + PTX groups the heart rate (365 .45 +/- 6.62 and 357.27 +/- 7.23 b.p.m., respectively; P < 0.05) were found to be significantly higher than initial values, Serum creatinine levels increased significantly in the CsA alone group (1.40 +/- 0.11 mg/dL; P < 0.01) compared with control values (0.81 +/- 0.04 mg/dL). T his increase was prevented by co-treatment with PTX (serum creatinine 1.11 +/- 0.10 mg/dL; P < 0.05). Total [Tc-99m]-DTPA percentage renal u ptake, as an index of glomerular filtration rate (GFR), was markedly a nd significantly lower in the CsA alone group (10.01 +/- 0.79%; P < 0. 01) than in the control group (18.19 +/- 1.32%). Pentoxifylline co-tre atment attenuated this decrease compared with GFR in the CsA alone gro up (13.00 +/- 0.75%; P < 0.01).