Menadione-induced oxidative stress accelerates onset of Emory mouse cataract in vivo.
OBJECTIVE
We evaluated the effect of the free-radical generator, menadione, on the time of occurrence of cataract in the Emory mouse, a model for human cataract. Concomitant experiments were done to compare production and level of reactive metabolites of oxygen in the Emory mouse and its cataract resistant (CR) genetic control.


METHODS
Test and control mice were fed both a normal diet and a diet supplemented with menadione, and the lenses were evaluated for the time of occurrence of cataract and the level of membrane ATPases. Effects of menadione were determined on incubated lenses of Emory and CR mice, assaying reactive species of oxygen, levels of antioxidant enzymes, and formation of the lipid peroxidation product, malondialdehyde.


RESULTS
Systemic administration of menadione markedly accelerated the onset of Emory mouse cataract, and decreased ATPase activities suggested oxidative damage to membrane proteins. Cumulative levels of O2.-, H2O2, .OH and malondialdehyde were significantly higher than controls in the lenses incubated in the presence of menadione, showing that it generates oxidative stress. However, [GSH] in lenses decreased equally in test and control mice. The observed increases in catalase and glutathione peroxidase activities in the test lenses indicated an early protective response to oxidative insult.


CONCLUSIONS
Acceleration by menadione of the appearance of cataract in the Emory mouse demonstrates that oxidative stress is a risk factor in late-onset cataract. This quinone caused a greater increase in the production and levels of reactive metabolites of oxygen in Emory mice than in CR mice, indicative of a higher susceptibility of the former to oxidative insult.
Bhuyan
D K
DK
Membrane Biochemistry Laboratory, Edward S. Harkness Eye Institute, College of Physicians and Surgeons of Columbia University, New York 10032, USA.
Huang
X
X
Kuriakose
G
G
Garner
W H
WH
Bhuyan
K C
KC
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced*; D005260:Female; D007908:Lens, Crystalline / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014812:Vitamin K / Q000494:pharmacology
D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D014812:Vitamin K; D002374:Catalase; D013482:Superoxide Dismutase