ALLEVIATION OF EXPERIMENTAL CYCLOSPORINE-A NEPHROTOXICITY BY LOW-DOSE ASPIRIN 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 combination of both, or the appropriate drug vehicles daily for 14 days. Penal structure and function were assessed on day 0 (pretreatment) and on days 7 and 14. Compared to pretreatment results, CsA nephrotoxicity was characterized by increased plasma urea and creatinine concentrations and by moderate to severe microcalcification (MC) at the corticomedullary junction by day 14. The development of nephrotoxicity was also 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 remained relatively constant. Although both ASP and saline (ASP vehicle) -cotreated animals demonstrated significantly fewer plasma urea and creatinine concentrations compared to treatment with CsA alone, the severity of MC observed on day 14, was reduced only in the ASP cotreatment group. Trough whole blood CsA concentrations were similar at around 2400 ng/mL in all experimental groups. In addition, although a 2-fold increase in urine TxB(2) excretion was observed on days 7 and 10 following treatment with CsA/ASP, levels were significantly reduced compared to treatment with either CsA alone or CsA/saline (both P < 0.05).