ALLEVIATION OF EXPERIMENTAL CYCLOSPORINE-A NEPHROTOXICITY BY LOW-DOSEASPIRIN IN THE RAT

Groups of male Sprague-Dawley rats received either cyclosporin A (CsA; 25 mg/kg by gavage), low dose aspirin (ASP; 20 mg/kg by gavage), a co mbination of both, or the appropriate drug vehicles daily for 14 days. Penal structure and function were assessed on day 0 (pretreatment) an d on days 7 and 14. Compared to pretreatment results, CsA nephrotoxici ty was characterized by increased plasma urea and creatinine concentra tions and by moderate to severe microcalcification (MC) at the cortico medullary junction by day 14. The development of nephrotoxicity was al so associated with a 5-fold increase in urine thromboxane B-2 (TxB(2)) excretion by day 10, while that of 6-ketoprostaglandin F-1 alpha rema ined relatively constant. Although both ASP and saline (ASP vehicle) - cotreated animals demonstrated significantly fewer plasma urea and cre atinine concentrations compared to treatment with CsA alone, the sever ity of MC observed on day 14, was reduced only in the ASP cotreatment group. Trough whole blood CsA concentrations were similar at around 24 00 ng/mL in all experimental groups. In addition, although a 2-fold in crease in urine TxB(2) excretion was observed on days 7 and 10 followi ng treatment with CsA/ASP, levels were significantly reduced compared to treatment with either CsA alone or CsA/saline (both P < 0.05).