Prevention of oxidative stress to the retina by pyruvate. A preliminary report.
OBJECTIVE
Oxidative stress is considered to be a significant risk factor in the pathogenesis of many eye diseases associated with aging. The purpose of this study was to investigate the susceptibility of retinal tissue to reactive oxygen species (ROS)-induced damage, and to examine if this can be prevented by compounds having the ability to scavenge ROS as well as support the tissue bioenergetically via normal as well as anaplerotic metabolic pathways.


METHODS
Experiments were conducted on retinas isolated from CD-1 mice. The isolated retinas were incubated in Medium 199, generating ROS by the action of xanthine oxidase and uricase on xanthine. Parallel experiments were conducted in the presence of pyruvate (10 mM). The extent of oxidative damage to the tissue was assessed by determining the levels of glutathione. Malonaldehyde was used as an index of the peroxidative degradation of lipids.


RESULTS
Exposure of the tissue to ROS resulted in a significant decrease in its glutathione content. There was a simultaneous increase in the level of malonaldehyde. These effects were substantially attenuated by pyruvate.


CONCLUSIONS
While ROS has been previously implicated in the genesis of many aging diseases of the retina, methods to prevent or treat them are currently in their infancy. The present investigations suggest that this can be accomplished by the use of certain compounds of endogenous origin, such as pyruvate, which have the dual properties of acting as ROS scavengers while also acting as metabolic agonists. By virtue of its oxyradical scavenging property, it is expected to inhibit the oxidative degradation of polyunsaturated fatty acids required to maintain the structural and functional integrity of the tissue.
Hegde
Kavita R
KR
Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, Md. 21201, USA.
Varma
Shambhu D
SD
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000633:toxicity; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013053:Spectrophotometry; D013858:Thiobarbiturates / Q000378:metabolism; D016896:Treatment Outcome
D015415:Biomarkers; D017382:Reactive Oxygen Species; D013858:Thiobarbiturates; D008315:Malondialdehyde; D019289:Pyruvic Acid; C029684:thiobarbituric acid