Preventive effect of isocitrate on glucocorticoid-induced cataract formation of developing chick embryo.
Glucocorticoid-induced cataract formation appears to proceed via oxidation or peroxidation steps possibly caused by multiple activities of glucocorticoid in the living system. Attempts were made to modify GC-induced metabolic changes and prevent cataract formation using intermediates of the citric acid cycle. The compounds were applied to the embryos at 3, 10 and 20 hr after the administration of hydrocortisone succinate sodium (HC:0.25 mumol/egg) to 15-day-old eggs. At 48 hr after HC treatment the lenses were classified and analyzed. Almost all lenses were classified as stage IV-V (greater than 94%). However, the application of sodium isocitrate (IC:15 mumol/egg) which was the most potent among several intermediates tested showed a significant preventive effect against cataract formation. The administration of IC prevented the decline of GSH, the elevations of LPO and reduced the marked elevation of glucose in the lens caused by HC. The IC treatment also diminished the elevation of LPO in blood and liver. The above effects by IC on HC-induced events may be due to the action of IC in preventing the early decline of hepatic GSH caused by HC. Possibly IC was utilized as an intermediate of the citric acid cycle and a substrate for isocitrate dehydrogenase in cytosol to modify GC-induced metabolic changes.
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
J W
JW
Lee
M
M
Iwatsuru
H
H
Nishigori
D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000517:prevention & control*; D002642:Chick Embryo; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006854:Hydrocortisone / Q000031:analogs & derivatives; D007523:Isocitrates / Q000627:therapeutic use*; D007908:Lens, Crystalline / Q000187:drug effects / Q000473:pathology; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects
D007523:Isocitrates; D008054:Lipid Peroxides; C034219:isocitric acid; D005978:Glutathione; D005947:Glucose; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone