TY - JOUR
T1 - Alleviation of experimental cyclosporin A nephrotoxicity by low dose aspirin in the rat
AU - Adams, K. E.
AU - Brown, P. A.J.
AU - Heys, S. D.
AU - Whiting, P. H.
PY - 1993/12/3
Y1 - 1993/12/3
N2 - Groups of male Sprague-Dawley rats recieved 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. Renal 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 B2 (TxB2) excretion by day 10, while that of 6-ketoprostaglandin F1α remained relatively constant. Although both ASP and saline (ASP vehicle) -cotreated animals demonstrated significantly lower 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 TxB2 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).
AB - Groups of male Sprague-Dawley rats recieved 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. Renal 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 B2 (TxB2) excretion by day 10, while that of 6-ketoprostaglandin F1α remained relatively constant. Although both ASP and saline (ASP vehicle) -cotreated animals demonstrated significantly lower 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 TxB2 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).
UR - http://www.scopus.com/inward/record.url?scp=0027442714&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(93)90655-G
DO - 10.1016/0006-2952(93)90655-G
M3 - Article
C2 - 8267661
AN - SCOPUS:0027442714
SN - 0006-2952
VL - 46
SP - 2104
EP - 2108
JO - BIOCHEMICAL PHARMACOLOGY
JF - BIOCHEMICAL PHARMACOLOGY
IS - 11
ER -