caa a22 4500 475772571 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s001250051488 doi (NATIONALLICENCE)springer-10.1007/s001250051488 Evaluation of an aldose reductase inhibitor on lens metabolism, ATPases and antioxidative defense in streptozotocin-diabetic rats: an intervention study [Elektronische Daten] [I. G. Obrosova, L. Fathallah] Aims/hypothesis. Aldose reductase inhibitors (ARIs) prevent biochemical abnormalities associated with diabetic complications. We evaluated whether a short-term intervention with an adequate dose of ARI, introduced at the very early, precataractous stage, reversed diabetes-induced metabolic imbalances, down-regulation of ATPases and oxidative stress in the lens. Methods. The groups included mature control and streptozotocin-diabetic rats treated with or without ARI sorbinil (65 mg · kg-1· day-1, in the diet, for 2 weeks after 4 weeks of untreated diabetes). Free cytosolic NAD+:NADH and NADP+:NADPH ratios were calculated from the lactate dehydrogenase and malic enzyme systems. Concentrations of metabolites and adenine nucleotides, Na+/K+-ATPase, H+-ATPase and Ca++-independent Mg++-ATPase activities and variables of oxidative stress were measured in individual lenses. Results. Sorbinil treatment essentially corrected diabetes-induced sorbitol and fructose accumulation, myo-inositol depletion, decrease in free cytosolic NAD+:NADH ratio and energy deficiency. Malondialdehyde accumulation, reduced glutathione depletion and the increase in oxidized glutathione:reduced glutathione ratio were partially corrected. Free cytosolic NADP+:NADPH ratio and 4-hydroxyalkenal concentrations were similarly increased in diabetic rats treated with or without ARI. Sorbinil did not counteract diabetes-induced down-regulation of the three ATPase activities. Conclusion/interpretation. All biochemical changes assessed in our study are known to be prevented by ARIs. Despite the essential normalization of the sorbitol pathway activity, only part of them were, however, reversed by the ARI treatment introduced at the very early, i. e. precataractous, stage of diabetes. Therefore, intervention studies can easily underestimate the importance of aldose reductase in the pathogenesis of diabetic complications and should be interpreted with caution. [Diabetologia (2000) 43: 1048-1055] Springer-Verlag Berlin Heidelberg, 2000 Keywords Aldose reductase nationallicence ATPase activities nationallicence energy metabolism nationallicence lens nationallicence NAD(P)-redox state nationallicence oxidative stress nationallicence rat nationallicence reversal study nationallicence sorbinil nationallicence streptozotocin-diabetes nationallicence Obrosova I. G. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA, US aut Fathallah L. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA, US aut https://doi.org/10.1007/s001250051488 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051488 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Obrosova I. G. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA, US aut NATIONALLICENCE 700 1- Fathallah L. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer