Effects of the lipid peroxidation inhibitor tirilazed mesylate (U-74006F) on gerbil brain eicosanoid levels following ischemia and reperfusion

Paula K. Andrus, Bruce M. Taylor, Frank F. Sun, Edward D. Hall

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The present study measured the production of eicosanoids in the gerbil brain durin reperfusion after either a 3-h unilateral carotid occlusion (UCO, model of focal ischemia) or a 10-min bilateral carotid occlusion (BCO, model of global ischemia). Arachidonic acid (AA) metabolites were examined to determine if pretreatment with the 21-aminosteroid lipid peroxidation inhibitor U-74006F (tirilazad mesylate) could influence postreperfusion synthesis of brain eicosanoids. In the 3-h UCO focal ischemia model, there was an early (5-min) postreperfusion elevation in brain levels of PGF, TXB2 and LTC4 (P < 0.05 vs. sham for all three eicosanoids). LTB4 also rose but not significantly. On the other hand, PGE2 and 6-keto-PGF tended to decrease during ischemia and at 5-min postreperfusion (P < 0.05 vs. sham for PGE2). Pretreatment with known neuroprotective doses of U-74006F in this model (10 mg/kg i.p. 10 min before and again immediately upon reperfusion) did not affect the increase in PGF or TXB2 but significantly blunted the elevations in LTC4 and LTB4. The postreperfusion decrease in PGE2 was also attenuated. In the 10-min BCO global ischemia model, there was also an increase in each of the measured eicosanoids, except LTB4, at 5 min aafter reperfusion. Pretreatment with U-74006F (10 mg/kg i.p. 10 min before ischemia) selectively decreased the rise in LTC4 but did not significantly affect the other eicosanoids. In contrast, the antioxidant actually caused a significant enhancement of the postreperfusion increase in PGE2 vs. vehicle-treated animals. The effects of U-74006F on postreperfusion eicosanoid synthesis are consistent with the lipid antioxidant properties of this compound. In particular, the attenuation of leukotriene levels is most likelu a reflection of a decrease in postreperfusion lipid peroxidation, since lipid peroxides are potent activators of 5-lipoxygenase.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalBrain Research
Issue number1-2
StatePublished - Oct 3 1994


  • 21-Aminosteroid
  • Leukotriene
  • Prostaglandin
  • Tirilazad mesylate

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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