ABSTRACT
PURPOSE: Histamine and nitric oxide (NO) play pivotal roles in ocular surface hypersensitivity reactions, whereas the activity of their metabolic enzymes diamine oxidase (DAO) and NO synthase (NOS) may affect their function. This study aimed at investigating the effects of ocular administration of aminoguanidine (AMG), a multiple action DAO and NOS inhibitor, on the conjunctival histamine and nitrite levels in a model of experimental conjunctivitis. METHODS: AMG, at 0.81, 81 or 81×10(3) µM, was instilled into the lower conjunctival fornix of normal and compound 48/80 (C48/80)-challenged eyes of male Wistar rats in the absence or presence of 40 mg/mL disodium cromoglycate. Histamine and nitrite were quantified in the conjunctival homogenate and lavage fluid 45 min and 6 h postchallenge, respectively. RESULTS: AMG induced no significant alterations in basal histamine and nitrite levels in the normal rat eye. In experimental conjunctivitis, AMG failed to modify the reduction in histamine content and partially circumvented the increases in nitrite levels observed during the early and late phase reactions, respectively. In the presence of disodium cromoglycate, AMG significantly increased the levels of both proinflammatory mediators in the normal rat eye. CONCLUSIONS: The data suggested that DAO may not be the main route of in situ histamine catabolism in the normal and C48/80-challenged rat conjunctiva, whereas NOS contributes to the phenotypic alterations observed in mast cell-dependent conjunctivitis. Mast cell stabilizing agents and AMG-modulated systems seem to interact through yet undefined mechanisms in the different phases of ocular hypersensitivity reactions.
