Effects of endotoxin and anti-inflammatory agents on superoxide dismutase in the rabbit iris.

Superoxide dismutase activity (SOD) was measured in the irides of control animals and 24 h after the intravitreal administration of Escherichia coli endotoxin. A 3-fold increase in SOD was noted (p less than 0.001). To protect against the inflammatory process, either topical dexamethasone (Dex) or medrysone (Med) was administered t.i.d. for 2 days before and 1 day after endotoxin. Although Dex prevented the iritis seen with endotoxin alone, a 2-fold increase in SOD was measured (p less than 0.001). The Med regimen failed to prevent the signs of endotoxin-induced ocular inflammation yet also reduced the induction of SOD (p less than 0.02). The phospholipase A2 inhibitor, quinacrine, and the lipoxygenase inhibitor, nordihydroguaiaretic acid, blocked the induction of SOD, while the cyclooxygenase inhibitor, indomethacin, did not. Thus, it appears that the induction SOD may be mediated by a product of the lipoxygenase pathway.

The effects of endotoxin, glucocorticoids and prostaglandin metabolism in the rabbit iris.

Superoxide dismutase activity (SOD) was measured in the irides of control animals (n = 16) and 24 hours after the intravitreal administration of endotoxin (n = 12). Nearly a twofold increase in SOD was noted in the endotoxin-treated animals (p less than 0.001). In order to assess the induction of SOD while protecting against the inflammatory process, topical dexamethasone (dex) was administered t.i.d. for 2 days before and 1 day after endotoxin (n = 6). Dex prevented the conjunctival hyperemia, vascular injection and iritis seen with endotoxin treatment alone and blocked the induction of SOD. A similar medrysone (med) application (n = 4) failed to prevent the visible signs of ocular inflammation yet also blocked the elevation of SOD. Pretreatment with either of the cyclooxygenase inhibitors, indomethacin (n = 4) or aspirin (n = 7), failed to block the induction in SOD (p less than 0.001 and p less than 0.01, respectively). However, the induction of SOD was prevented by the phospholipase A2 inhibitor, quinacrine, and the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). The data indicate that a product of the lipoxygenase pathway may be mediating the induction of SOD seen with endotoxin-induced ocular inflammation.

The effects of ascorbate, 3-aminotriazole, and 1,3-bis-(2-chloroethyl)-1-nitrosourea on hydrogen peroxide levels in the rabbit aqueous humor.

3-aminotriazole (3-AT), a catalase inhibitor, given to pigmented rabbits in 0.2% drinking solution for 43 days, produced cataractous changes and over a 50% reduction in iris and ciliary process catalase activity. Aqueous H2O2 levels were suppressed by 60% which correlated with a 77% reduction in aqueous ascorbate concentration. Intravenous 3-AT at 1.0 g/kg body weight had no effect on either aqueous ascorbate or H2O2 levels. BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea) was given intravitreally to rabbits: 3.0 mg suppressed iris glutathione reductase activity by 80%, but only increased the oxidized glutathione/total glutathione ratio to 26% from 18%. Both aqueous ascorbate and H2O2 levels were unaltered at 48 hours. Buthionine sulfoximine (BSO) was given intravitreally; at 48 hours after 4.0 mg BSO, iris-ciliary body total glutathione levels were reduced by 80%, aqueous ascorbate levels were reduced by 53%, and aqueous H2O2 levels were unaltered. A direct correlation seems to exist between aqueous humor ascorbate and H2O2 concentrations, even during suppression of tissue catalase activity. Changes in glutathione status cause peroxide levels to be greater than predicted from the aqueous ascorbate concentration.