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The cyclooxygenase and lipoxygenase inhibitor BW755C protects rats against kainic acid-induced seizures and neurotoxicity.

Abstract
In this study the effect of the anti-inflammatory drugs indomethacin, ibuprofen, ebselen (PZ 51, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one), and BW755C (3-amino-1-(m-(trifluoromethyl-phenyl)-2-pyrazoline) on kainic acid (KA)-induced behavioral and neurochemical changes in rats was investigated. Rats injected with KA (10 mg/kg s.c.) developed seizure activity with a 20% mortality within the first 4 h and neuronal degeneration in the limbic system after 3 days. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.) augmented KA-induced epileptic activity and increased the mortality in status epilepticus to 80%. Another cyclooxygenase inhibitor, ibuprofen (20 mg/kg i.p.), and the lipoxygenase inhibitor ebselen (20 mg/kg i.p.) showed no effect on KA-induced symptoms and neurochemical changes. Application of the cyclooxygenase/lipoxygenase inhibitor BW755C (40 mg/kg i.p.) reduced the severity of seizures and protected significantly from irreversible brain lesions induced by KA. The marked reduction of glutamate decarboxylase (GAD; 53.3 +/- 12.2% of control) and choline acetyltransferase (ChAT; 60.9 +/- 9.1% of control) activities in amygdala/pyriform cortex and GAD activity in hippocampus (69.4 +/- 5.6% of control) observed 3 days after KA injection was abolished by BW755C treatment. Histopathological analyses of brain tissue showed that treatment with BW755C prevented the KA-induced nerve cell degeneration, edema, hemorrhages, and tissue necrosis in amygdala/pyriform cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsH Baran, K Vass, H Lassmann, O Hornykiewicz
JournalBrain research (Brain Res) Vol. 646 Issue 2 Pg. 201-6 (May 23 1994) ISSN: 0006-8993 [Print] Netherlands
PMID8069664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Azoles
  • Cyclooxygenase Inhibitors
  • Isoindoles
  • Lipoxygenase Inhibitors
  • Organoselenium Compounds
  • ebselen
  • 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
  • Choline O-Acetyltransferase
  • Glutamate Decarboxylase
  • Kainic Acid
  • Ibuprofen
  • Indomethacin
Topics
  • 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine (pharmacology)
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Azoles (pharmacology)
  • Brain (drug effects, enzymology, pathology)
  • Choline O-Acetyltransferase (metabolism)
  • Cyclooxygenase Inhibitors (pharmacology)
  • Glutamate Decarboxylase (metabolism)
  • Ibuprofen (pharmacology)
  • Indomethacin (pharmacology)
  • Isoindoles
  • Kainic Acid (antagonists & inhibitors, toxicity)
  • Lipoxygenase Inhibitors (pharmacology)
  • Male
  • Organ Specificity
  • Organoselenium Compounds (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Seizures (chemically induced, prevention & control)

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