Diabetes-induced changes in lens antioxidant status, glucose utilization and energy metabolism: effect of DL-?-lipoic acid
| Autor: | I. G. Obrosova, Xianghui Cao, M. J. Stevens, Douglas A. Greene |
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| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Fructose Antioxidants Diabetes Mellitus Experimental chemistry.chemical_compound Polyol pathway Adenine nucleotide Internal medicine Lactate dehydrogenase Lens Crystalline Internal Medicine medicine Animals Sorbitol Glycolysis Rats Wistar Dihydroxyacetone phosphate Thioctic Acid Adenine Nucleotides NAD Glutathione Rats Oxidative Stress Glucose Endocrinology Glycerol-3-phosphate dehydrogenase chemistry Biochemistry NAD+ kinase Energy Metabolism NADP |
| Zdroj: | Diabetologia. 41:1442-1450 |
| ISSN: | 1432-0428 0012-186X |
| Popis: | Summary The study was aimed at evaluating changes in lens antioxidant status, glucose utilization, redox state of free cytosolic NAD(P)-couples and adenine nucleotides in rats with 6-week streptozotocin-induced diabetes, and to assess a possibility of preventing them by dl-a-lipoic acid. Rats were divided into control and diabetic groups treated with and without dl-a-lipoic acid (100 mg ◊ kg body weight ‐1 ◊ day ‐1 , i. p.). The concentrations of glucose, sorbitol, fructose, myo-inositol, oxidized glutathione, glycolytic intermediates, malate, a-glycerophosphate, 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 the lactate dehydrogenase and malic enzyme systems. Sorbitol pathway metabolites were found to increase, and antioxidant concentrations were reduced in diabetic rats compared with controls. The profile of glycolytic intermediates (increase in glucose 6-phosphate and fructose 6-phosphate, decrease in fructose1,6diphosphate, increase in dihydroxyacetone phosphate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate, and no change in lactate), and 5.9-fold increase in a-glycerophosphate suggest diabetes-induced inhibition of glycolysis. Free cytosolic NAD + :NADH ratios, ATP levels, ATP/ADP · inorganic phosphate (Pi), and adenylate charge were reduced in diabetic rats while free cytosolic NADP + :NADPH ratios were elevated. Diabetes-induced changes in the concentrations of antioxidants, key glycolytic intermediates, free cytosolic NAD + :NADH ratios, and energy status were partially prevented by dl-a-lipoic acid, while sorbitol pathway metabolites and free cytosolic NADP + :NADPH ratios remained unaffected. In conclusion, diabetes-induced impairment of lens antioxidative defense, glucose intermediary metabolism via glycolysis, energy status and redox changes are partially prevented by dl-a-lipoic acid. The findings support the important role of oxidative stress in lens metabolic imbalances in diabetes. [Diabetologia (1998) 41: 1442‐1450] |
| Databáze: | OpenAIRE |
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