Additive effect of nitric oxide and prostaglandin-E2 synthesis inhibitors in endotoxin-induced uveitis in the rabbit.
The involvement of nitric oxide (NO) and prostaglandin E2 (PGE2) was investigated in a model of intraocular inflammation induced by intravitreal injection of endotoxin (lipopolysaccharide, LPS, 10 ng) in rabbits. The severity of uveitis, the myeloperoxidase (MPO) activity in iris-ciliary body, and the protein concentration in aqueous humor were determined. Nitric oxide synthase (NOS) and cyclooxygenase (COX) activities were assessed respectively by nitrite and PGE2 levels in aqueous humor. Treatment with inhibitors of NOS (NG-nitro-L-arginine methyl ester, L-NAME, 50 mg/kp i.p.) or COX (diclofenac, 30 micrograms, topically), alone or in combination, were compared to a saline-treated group. Diclofenac or L-NAME alone reduced or delayed the intensity of uveitis, and partially decreased the protein concentration in aqueous humor; diclofenac, but not L-NAME, partially reduced the polymorphonuclear leukocyte infiltration in the iris ciliary body as indicated by the MPO activity. Treatment with both inhibitors in combination diminished the clinical uveitis, the disruption of the blood-aqueous barrier and the MPO activity in the iris-ciliary body. We conclude that NO and PGE2 have additive effects in endotoxin-induced uveitis in rabbits, and that the inhibition of both pathways would improve the therapeutical management of uveitis.
Bellot
J L
JL
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad de Alicante, Spain.
Palmero
M
M
García-Cabanes
C
C
Espí
R
R
Hariton
C
C
Orts
A
A
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002924:Ciliary Body / Q000187:drug effects / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015232:Dinoprostone / Q000502:physiology*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D004008:Diclofenac; D009569:Nitric Oxide; D001120:Arginine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester