Abstract:
:Renal vasoconstriction has been implicated as a major contributing factor for the nephrotoxic effects of cyclosporine. In an attempt to assess the relative contribution of thromboxane (Tx), the effects of coadministering CsA with the selective Tx synthetase inhibitor, Dazmegrel (DAZ) (Pfizer, Inc.), were determined. Rats were treated orally with 50 mg/kg of DAZ plus 50 mg/kg of CsA and various indicators of nephrotoxicity and efficacy were assessed. Animals treated with CsA + DAZ had a normalization of renal TxB2 synthesis as compared with animals treated with CsA alone (160 vs. 338 pg/ml). Kidney proximal tubule damage following CsA treatment alone was also reduced in animals coadministered DAZ, as indicated by reduced urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) (9.7 vs. 14.1 U/g creatinine) and by histological examination of kidney sections. However, DAZ did not affect blood levels of CsA nor its efficacious activity in a model of experimental allergic encephalomyelitis (EAE). These studies suggest a major role of elevated thromboxane production in the acute nephrotoxic effects of CsA and demonstrate a reduction in this toxicity by DAZ without altering CsA's efficacious activity.
journal_name
Transplantationjournal_title
Transplantationauthors
Gladue RP,Newborg MFdoi
10.1097/00007890-199111000-00016subject
Has Abstractpub_date
1991-11-01 00:00:00pages
837-41issue
5eissn
0041-1337issn
1534-6080journal_volume
52pub_type
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