To evaluate the role for aldose reductase-linked mechanisms in diabetes-induced changes in lens intermediary and energy metabolism and to make a comparative evaluation of structurally different ARIs vs SDI on elderly metabolic imbalances, experiments were performed on rats, divided into control and diabetic groups. Diabetic groups included 10-day diabetic rats treated with/without one of the two ARIs as well as 4-,7-, and 10-day diabetic rats treated with/without SDI. Levels of glucose, glycolytic intermediates, (-glycerophosphate (GP), and adenine nucleotides were assayed spectrofluorometrically in individual lenses by enzymatic procedures; levels of sorbitol, fructose, and myo-inositol were quantified by GC/MS. Accumulation of sorbitol and the depletion of myo-inositol in diabetic rats were substantially prevented by tolrestat and were completely prevented by sorbinil. Both ARIs prevented decreases in levels of key glycolytic intermediates and free cytosolic NAD+/NADH r atios as well as accumulation of GP and impairment of energy metabolism. All diabetes-induced changes in lens intermediary metabolism are mediated by aldose reductase-involved mechanisms and are prevented by structurally different ARIs. Further depletion of myo-inositol and GSH as well as adverse rather than beneficial effect on glycolysis and energy metabolism is achieved by potentiation of osmotic stress due to sorbitol dehydrogenase inhibition in spite of an improvement of the lens redox state.
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