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BENEFICIAL EFFECTS OF PENTOXIFYLLINE ON CYCLOSPORINE‐ INDUCED NEPHROTOXICITY
Author(s) -
Kaputlu İrfan,
Şadan Gülay,
Karayalçin Binnur,
Boz Adil
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb01203.x
Subject(s) - pentoxifylline , renal function , nephrotoxicity , creatinine , medicine , blood pressure , transplantation , urology , endocrinology , kidney , pharmacology
SUMMARY 1. Hypertension and renal failure are the two most common and severe complications 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 studied. 2. The first group of rats (n = 11) received daily injections of CsA (15 mg/kg, i.m.) and PTX (45 mg/kg, i.p., b.i.d.), the second group of rats in = 11) was treated with CsA only and the third group of rats (n = 11) served as the control group (vehicle treatment). 3. Whole blood CsA levels were similar in CsA + PTX and CsA alone groups. Although CsA treatment significantly increased mean arterial blood pressure (110.00 ± 2.48 nunHg; P<0.01), there was no significant increase in the PTX co‐treated group (104.09 ± 2.96 mm Hg) 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). This increase was prevented by co‐treatment with PTX (serum creatinine 1.11 ± 0.10 mg/dL; P < 0.05). Total [ 99m Tcl‐DTPA percentage renal uptake, as an index of glomerular filtration rate (GFR), was markedly and significantly lower in the CsA alone group (10.01 ± 0.79%; P < 0.01) than in the control group (18.19 ± 132%). Pentoxifylline co‐treatment attenuated this decrease compared with GFR in the CsA alone group (13.00 ± 0.75%; P < 0.01). 4. These results suggest that the co‐administration of PTX with CsA may prevent the dose‐limiting toxic effects of CsA therapy.