The effect of a new lipoxygenase inhibitor on the production of arachidonic acid metabolites during experimental herpes simplex keratitis.
We have studied the effect of a new, selective lipoxygenase inhibitor, TEI-1338, on alterations in arachidonic acid (20:4) metabolism and breakdown of the blood-aqueous barrier during herpes simplex virus (HSV) infection of the rabbit cornea. Synthesis of cyclooxygenase products (prostaglandins) and the lipoxygenase products, hydroxyeicosatetraenoic acids (HETEs) and leukotriene B4 (LTB4), was measured in vitro by assessing conversion of 1-14C-20:4 in infected and non-infected corneas. TEI-1338 inhibited infection-stimulated lipoxygenase activity in a concentration-dependent manner, without affecting cyclooxygenase activity. Treatment of herpes infection in vivo with TEI-1338 (ocular drops) reduced leakage of protein into aqueous humor, a measure of inflammation-induced deterioration of the blood aqueous barrier. These data indicate that drugs that selectively inhibit lipoxygenase may be useful in the treatment of the inflammatory consequences of herpes keratitis, without exacerbating the infectious process.
Limberg
M B
MB
Department of Ophthalmology, LSU Eye Center, New Orleans 70112.
Birkle
D L
DL
Bazan
H E
HE
Kaufman
H E
HE
Bazan
N G
NG
D000287:Administration, Topical; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D007635:Keratitis, Dendritic; D007975:Leukotriene B4 / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D018139:Simplexvirus
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D009281:Naphthalenes; D011453:Prostaglandins; C058972:TEI 1338; D007975:Leukotriene B4