Inhibition of the Alkali Burn-Induced Lipoxygenation of Arachidonic Acid in the Rabbit Cornea In Vivo by a Platelet Activating Factor Antagonist

ABSTRACT

We have evaluated the involvement of 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor, PAF), a membrane derived lipid mediator, in the inflammatory response of the anterior segment of the rabbit eye after corneal injury. The action of BN 52021, an antagonist of PAF receptor, was tested in vivo in models of corneal injury by alkali burn. The sodium salt of 1-¹⁴C-arachidonic acid was injected in the anterior chamber and the production of labeled prostaglandins and hydroxyeicosatetraenoic acid (HETE) was monitored as an index of the activation of the cyclooxygenase and lipoxygenase pathways. Topically applied BN 52021 produced a specific inhibition of the formation of labeled 5- and 12-HETE. This inhibition was maximal when the drug was applied during the first few hours after the injury. The drug does not affect the increased protein concentration in the aqueous humor after injury. These results suggest involvement of PAF in the inflammatory response in the cornea that could be blocked by the antagonist.