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The effect of inhibition of glutathione reductase on the detoxification of H2O2 by rabbit lens.
Invest Ophthalmol Vis Sci. 1983 Jan; 24(1):113-8.IO

Abstract

Mechanisms by which the lens protects against H2O2 are believed to include the metabolism of glutathione (GSH). In the present study, rabbit lenses were exposed to constant concentrations of H2O2 (0.01 to 0.1 mM) that were maintained in culture media with the use of a peristaltic pump. The rate at which H2O2 entered the lens was proportional to its concentration in the medium and reached 2.6 mumol H2O2/lens/3 hr at 0.1 mM H2O2. Up to 0.06 mM H2O2, a concentration that approximates that present in normal rabbit aqueous humor, the activity of the hexose monophosphate shunt (HMPS) increased linearly with no significant decrease in the concentration of lens GSH. However, at 0.1 mM H2O2, there was indication of oxidative damage to the lens as shown by a sharp decrease in HMPS activity and a coincident drop in the concentration of GSH. Pretreatment of lenses with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase (GR), blocked the normal threefold stimulation of HMPS activity occurring in the presence of 0.06 mM H2O2 and resulted in accumulation of oxidized GSH. This result demonstrated the inability of H2O2 to react directly with NADPH in the lens. BCNU was shown not to affect the potential of the HMPS to respond to compounds other than H2O2 since it did not alter methylene blue-stimulation of HMPS activity. The study supports the hypothesis that detoxification of H2O2 in the aqueous humor is linked to the metabolism of GSH in the lens and demonstrates that lenses with impaired GR activity are more susceptible to oxidative damage by peroxide.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

6826306

Citation

Giblin, F J., and J P. McCready. "The Effect of Inhibition of Glutathione Reductase On the Detoxification of H2O2 By Rabbit Lens." Investigative Ophthalmology & Visual Science, vol. 24, no. 1, 1983, pp. 113-8.
Giblin FJ, McCready JP. The effect of inhibition of glutathione reductase on the detoxification of H2O2 by rabbit lens. Invest Ophthalmol Vis Sci. 1983;24(1):113-8.
Giblin, F. J., & McCready, J. P. (1983). The effect of inhibition of glutathione reductase on the detoxification of H2O2 by rabbit lens. Investigative Ophthalmology & Visual Science, 24(1), 113-8.
Giblin FJ, McCready JP. The Effect of Inhibition of Glutathione Reductase On the Detoxification of H2O2 By Rabbit Lens. Invest Ophthalmol Vis Sci. 1983;24(1):113-8. PubMed PMID: 6826306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of inhibition of glutathione reductase on the detoxification of H2O2 by rabbit lens. AU - Giblin,F J, AU - McCready,J P, PY - 1983/1/1/pubmed PY - 1983/1/1/medline PY - 1983/1/1/entrez SP - 113 EP - 8 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 24 IS - 1 N2 - Mechanisms by which the lens protects against H2O2 are believed to include the metabolism of glutathione (GSH). In the present study, rabbit lenses were exposed to constant concentrations of H2O2 (0.01 to 0.1 mM) that were maintained in culture media with the use of a peristaltic pump. The rate at which H2O2 entered the lens was proportional to its concentration in the medium and reached 2.6 mumol H2O2/lens/3 hr at 0.1 mM H2O2. Up to 0.06 mM H2O2, a concentration that approximates that present in normal rabbit aqueous humor, the activity of the hexose monophosphate shunt (HMPS) increased linearly with no significant decrease in the concentration of lens GSH. However, at 0.1 mM H2O2, there was indication of oxidative damage to the lens as shown by a sharp decrease in HMPS activity and a coincident drop in the concentration of GSH. Pretreatment of lenses with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase (GR), blocked the normal threefold stimulation of HMPS activity occurring in the presence of 0.06 mM H2O2 and resulted in accumulation of oxidized GSH. This result demonstrated the inability of H2O2 to react directly with NADPH in the lens. BCNU was shown not to affect the potential of the HMPS to respond to compounds other than H2O2 since it did not alter methylene blue-stimulation of HMPS activity. The study supports the hypothesis that detoxification of H2O2 in the aqueous humor is linked to the metabolism of GSH in the lens and demonstrates that lenses with impaired GR activity are more susceptible to oxidative damage by peroxide. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/6826306/The_effect_of_inhibition_of_glutathione_reductase_on_the_detoxification_of_H2O2_by_rabbit_lens_ L2 - https://iovs.arvojournals.org/article.aspx?volume=24&issue=1&page=113 DB - PRIME DP - Unbound Medicine ER -