Diabetes-induced changes in lens antioxidant status, glucose utilization and energy metabolism: effect of DL-alpha-lipoic acid

The study was aimed at evaluating changes in lens antioxidant status, gluco se utilization, redox state of free cytosolic NAD(P)-couples and adenine nu cleotides in rats with 6-week streptozotocin-induced diabetes. and to asses s a possibility of preventing them by DL-alpha-lipoic acid. Rats were divid ed into control and diabetic groups treated with and without DL-alpha-lipoi c acid (100 mg kg body weight(-1) . day(-1), i.p.). The concentrations of g lucose, sorbitol, fructose, myo-inositol, oxidized glutathione, glycolytic intermediates, malate, alpha-glycerophosphale, and adenine nucleotides were assayed in individual lenses spectrofluorometrically by enzymatic methods, reduced glutathione and ascorbate - colorimetrically, and taurine by HPLC. Free cytosolic NAD(+):NADH and NADP(+):NADPH ratios were calculated from t he lactate dehydrogenase and malic enzyme systems. Sorbitol pathway metabol ites were found to increase, and antioxidant concentrations were reduced in diabetic rats compared with controls. The profile of glycolytic intermedia tes (increase in glucose 6-phosphate and fructose 6-phosphate, decrease in fructose1.6-diphosphate, increase in dihydroxyacetone phosphate, 3-phosphog lycerate, phosphoenolpyruvate, pyruvate. and no change in lactate), and 5.9 -fold increase in alpha-glycerophosphate suggest diabetes-induced inhibitio n of glycolysis. Free cytosolic NAD(+): NADH ratios, ATP levels, ATP/ADP x inorganic phosphate (P-i), and adenylate charge were reduced in diabetic ra ts while free cytosolic NADP(+):NADPH ratios were elevated. Diabetes-induce d changes in the concentrations of antioxidants, key glycolytic intermediat es, free cytosolic NAD(+):NADH ratios, and energy status were partially pre vented by DL-alpha-lipoic acid, while sorbitol pathway metabolites and free cytosolic NADP(+):NADPH ratios remained unaffected. In conclusion, diabete s-induced impairment of lens antioxidative defense, glucose intermediary me tabolism via glycolysis, energy status and redox changes are partially prev ented by DL-alpha-lipoic acid. The findings support the important role of o xidative stress in lens metabolic imbalances in diabetes.