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The effects of inhibition of both glutathione synthesis and of glutathione reductase and catalase activities have been determined in the regulation of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in the anterior chamber of pigmented rabbits. Glutathione reductase inhibition using intravitreal 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) did not significantly alter either total glutathione or the percent oxidized glutathione fraction in the iris-ciliary body. Intravitreal buthionine sulfoximine (BSO) significantly reduced the total glutathione content of iris-ciliary body and corneal endothelium, while not altering the oxidized fraction. BCNU increased the oxidized fraction of glutathione in the aqueous humor from 22 to 63% without significantly altering total glutathione levels. BSO, however, reduced total glutathione by 70% in the aqueous humor, and the oxidized fraction doubled. Decreases in the reduced glutathione concentration caused by BSO correlate with increases in the normally stable ratio of H<sub>2</sub>O<sub>2</sub> to ascorbate concentrations in the aqueous humor, strongly suggesting that glutathione metabolism is correlated with H<sub>2</sub>O<sub>2</sub> regulation at endogenous levels of this oxidant. Both BSO and 3-aminotriazole (3AT) separately increased the half-time for the loss of exogenously added H<sub>2</sub>0<sub>2</sub> from the anterior chamber. BSO increased the half-time by 77% after 10 μl of 10 mMH<sub>2</sub>O<sub>2</sub> was injected intracamerally, while suppression of catalase activity with 3AT increased it by only 40%. With intracameral injections of 10 μl of either 25 or 50 mM H<sub>2</sub>O<sub>2</sub>, however, 3AT had a greater effect than BSO. The half-time values after 3AT pretreat-ment were 61 and 135% greater than control values at the concentrations of 25 and 50 mM H<sub>2</sub>O<sub>2</sub>, respectively; those after BSO pretreatment were at 14 and 78%. From these data we conclude that the glutathione redox system protects the anterior segment tissues from hydrogen peroxide at low concentrations of this oxidant, while catalase assumes a greater role at higher concentrations of hydrogen peroxide.
Ophthalmic Research – Karger
Published: Jan 1, 2009
Keywords: Aqueous humor; Catalase; Glutathione; Hydrogen peroxide
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