Cold injury, blood-brain barrier changes, and leukotriene synthesis: inhibition by phenidone.
Transcranial cold injury in rats and guinea pigs induced cerebral extravasation of albumin labeled with Evans blue dye or 125I, respective indicators of the area and amount of blood-brain barrier (BBB) disruption. Radioimmunoassay of brain extracts showed that cold injury induced leukotriene (LT)C4 in rat and guinea pig brains 15 min after injury. In guinea pigs, the LT synthesis inhibitor phenidone (30 mg/kg, i.p.) completely blocked cold-induced LTC4 in brain. Phenidone (30 and 100 mg/kg) also inhibited cerebral tissue accumulation of 125I-albumin and dye in rats and guinea pigs. Phenidone is reported to show antioxidant properties and selective lipoxygenase inhibition of arachidonic acid metabolism compared to cyclooxygenase inhibitors, meclofenamate sodium, and other nonsteroidal anti-inflammatory agents. Since several oxygen and hydroxyl radical scavengers and the cyclooxygenase inhibitor, meclofenamate sodium, did not inhibit protein extravasation, the findings support a role for LT as a mediator of cold-induced changes in BBB permeability in rats and guinea pigs and suggest that the inhibitory effects of phenidone on BBB permeability may be due to inhibition of LT production.
Robichaud
L J
LJ
Department of Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner Lambert Company, Ann Arbor, Michigan.
Marcoux
F W
FW
D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D003080:Cold Temperature; D005609:Free Radicals; D006168:Guinea Pigs; D015289:Leukotrienes / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis; D012711:Serum Albumin, Radio-Iodinated
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D005609:Free Radicals; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013189:SRS-A; D012711:Serum Albumin, Radio-Iodinated; D016718:Arachidonic Acid; C015429:phenidone