The protective effects of the thromboxane synthetase inhibitor Dazmegrel on nephrotoxicity in cyclosporine-treated rats.

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

Transplantation

journal_title

Transplantation

authors

Gladue RP,Newborg MF

doi

10.1097/00007890-199111000-00016

subject

Has Abstract

pub_date

1991-11-01 00:00:00

pages

837-41

issue

5

eissn

0041-1337

issn

1534-6080

journal_volume

52

pub_type

杂志文章
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    authors: Hannani D,Merlin E,Gabert F,Laurin D,Deméocq F,Chaperot L,Kanold J,Plumas J

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  • Identification of kidneys subjected to preretrieval warm ischemic injury by simultaneous monitoring of glomerular filtration and perfusate flow during hypothermic perfusion preservation.

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  • Immunoregulatory abnormalities in patients with Epstein-Barr virus-associated B cell lymphoproliferative disorders.

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    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

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  • Pharmacokinetics of methylprednisolone and rejection episodes in kidney transplant patients.

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    更新日期:1995-08-27 00:00:00

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    doi:10.1097/00007890-199402150-00022

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    authors: Tydén G,Brattström C,Lundgren G,Ostman J,Gunnarsson R,Groth CG

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  • Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection.

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  • CORM-401 Reduces Ischemia Reperfusion Injury in an Ex Vivo Renal Porcine Model of the Donation After Circulatory Death.

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  • Reversal of hyperglycemia in mice after subcutaneous transplantation of macroencapsulated islets.

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    authors: Tatarkiewicz K,Hollister-Lock J,Quickel RR,Colton CK,Bonner-Weir S,Weir GC

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    abstract::The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced...

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    authors: Dafoe DC,Campbell DA Jr,Rosenberg L,Merion RM,Ucros I,Vinik AI,Klandorf H,Turcotte JG

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  • Liver Transplantation for NASH-Related Hepatocellular Carcinoma Versus Non-NASH Etiologies of Hepatocellular Carcinoma.

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    pub_type: 杂志文章,多中心研究

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    更新日期:2018-04-01 00:00:00

  • Sirolimus delays recovery of rat kidney transplants after ischemia-reperfusion injury.

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    authors: Fuller TF,Freise CE,Serkova N,Niemann CU,Olson JL,Feng S

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    abstract:BACKGROUND:The authors studied the relationship between the dynamics of Epstein-Barr virus (EBV) load, CD8 T-cell activation and differentiation, and EBV-associated symptoms in 25 children after kidney transplantation (Tx). METHODS:Twenty-two patients were enrolled at the time of Tx and three at diagnosis of EBV-induc...

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    authors: Baudouin V,Dehée A,Pédron-Grossetete B,Ansart-Pirenne H,Haddad E,Maisin A,Loirat C,Sterkers G

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  • Intraoperative Hemodynamic Parameters and Acute Kidney Injury After Living Donor Liver Transplantation.

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    authors: Kim WH,Oh HW,Yang SM,Yu JH,Lee HC,Jung CW,Suh KS,Lee KH

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    pub_type: 杂志文章,随机对照试验

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  • Prolongation of cardiac xenograft survival in rats receiving cyclosporin A.

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  • Comparative long-term evaluation of tacrolimus and cyclosporine in pediatric liver transplantation.

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    doi:10.1097/00007890-199309000-00025

    authors: Zanker B,Jooss-Rüdiger J,Franz HE,Wagner H,Kabelitz D

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    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31816de49e

    authors: Jiang J,Salido EC,Guha C,Wang X,Moitra R,Liu L,Roy-Chowdhury J,Roy-Chowdhury N

    更新日期:2008-05-15 00:00:00

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