The 21-aminosteroid tirilazad mesylate can ameliorate inflammatory bowel disease in rats

Gang Yue, Frank F. Sun, Colin Dunn, Kingsley Yin, Patrick Y.K. Wong

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The 21-aminosteroid tirilazad mesylate (U74006F) is a lipophilic antioxidant and free radical scavenger that has been reported to attenuate brain or spinal cord injury caused by trauma, stroke, ischemia and reperfusion injury. In this study, we have examined the effect of U74006F in reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)- induced inflammatory bowel disease (IBD) in rats. To induce IBD, rats were given ethanolic TNBS intracolonically. Rats received either 1) TNBS and U74006F 2) TNBS and vehicle or 3) saline and vehicle. Rats were sacrificed 1, 2 and 3 weeks after IBD induction. Colon to body weight ratio (an index of tissue edema) was markedly increased in the vehicle-treated IBD rats after 1 week of administration of TNBS. The ratio was significantly lower after U74006F treatment and the trend remained even after 3 weeks of chronic inflammation. Myeloperoxidase (MPO) activity in vehicle-treated IBD rats was substantially increased compared with controls during the entire 3 weeks of the experiment. U74006F-treated animals had significantly reduced MPO activity (60% lower) when compared with vehicle-treated animals at the end of the second and third weeks. These observations were confirmed by histopathology studies showing reduced granulocyte infiltration after drug treatment. U74006F treatment decreased basal (by 70%) and fMLP stimulated (by 75%) superoxide generation from colonic tissue from IBD rats compared with vehicle treatment after 2 weeks, but there was no apparent difference in superoxide generation among all three groups after 3 weeks. The results of this study suggested that administration of U74006F effectively reduces the inflammatory parameters in this chronic rat model of IBD. As such, U74006F may be therapeutically beneficial for the treatment of IBD in humans.

Original languageEnglish (US)
Pages (from-to)265-270
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume276
Issue number1
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

Inflammatory Bowel Diseases
Trinitrobenzenes
Sulfonic Acids
Superoxides
Peroxidase
tirilazad
Free Radical Scavengers
Reperfusion Injury
Spinal Cord Injuries
Granulocytes
Edema
Colon
Antioxidants
Stroke
Body Weight
Inflammation
Wounds and Injuries
Brain
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Yue, Gang ; Sun, Frank F. ; Dunn, Colin ; Yin, Kingsley ; Wong, Patrick Y.K. / The 21-aminosteroid tirilazad mesylate can ameliorate inflammatory bowel disease in rats. In: Journal of Pharmacology and Experimental Therapeutics. 1996 ; Vol. 276, No. 1. pp. 265-270.
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abstract = "The 21-aminosteroid tirilazad mesylate (U74006F) is a lipophilic antioxidant and free radical scavenger that has been reported to attenuate brain or spinal cord injury caused by trauma, stroke, ischemia and reperfusion injury. In this study, we have examined the effect of U74006F in reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)- induced inflammatory bowel disease (IBD) in rats. To induce IBD, rats were given ethanolic TNBS intracolonically. Rats received either 1) TNBS and U74006F 2) TNBS and vehicle or 3) saline and vehicle. Rats were sacrificed 1, 2 and 3 weeks after IBD induction. Colon to body weight ratio (an index of tissue edema) was markedly increased in the vehicle-treated IBD rats after 1 week of administration of TNBS. The ratio was significantly lower after U74006F treatment and the trend remained even after 3 weeks of chronic inflammation. Myeloperoxidase (MPO) activity in vehicle-treated IBD rats was substantially increased compared with controls during the entire 3 weeks of the experiment. U74006F-treated animals had significantly reduced MPO activity (60{\%} lower) when compared with vehicle-treated animals at the end of the second and third weeks. These observations were confirmed by histopathology studies showing reduced granulocyte infiltration after drug treatment. U74006F treatment decreased basal (by 70{\%}) and fMLP stimulated (by 75{\%}) superoxide generation from colonic tissue from IBD rats compared with vehicle treatment after 2 weeks, but there was no apparent difference in superoxide generation among all three groups after 3 weeks. The results of this study suggested that administration of U74006F effectively reduces the inflammatory parameters in this chronic rat model of IBD. As such, U74006F may be therapeutically beneficial for the treatment of IBD in humans.",
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The 21-aminosteroid tirilazad mesylate can ameliorate inflammatory bowel disease in rats. / Yue, Gang; Sun, Frank F.; Dunn, Colin; Yin, Kingsley; Wong, Patrick Y.K.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 276, No. 1, 01.01.1996, p. 265-270.

Research output: Contribution to journalArticle

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