Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid peroxidation, and energy metabolism in diabetic precataractous lens

PURPOSE. To evaluate changes in glutathione and NAD(P)-redox status, taurin e and malondialdehyde (MDA) levels, glucose utilization, and energy metabol ism in diabetic precataractous lenses and to assess whether these changes c an be prevented with dietary taurine supplementation. METHODS. The experimental groups included control and streptozotocin-diabet ic rats with a 3-week duration of diabetes fed unsupplemented or taurine (1 % or 5%)-supplemented diets. The levels of glucose, sorbitol, fructose, myo -inositol, oxidized glutathione (GSSG), glycolytic intermediates, malate, a lpha-glycerophosphate, and adenine nucleotides were assayed in individual l enses spectrofluorometrically by enzymatic methods, reduced glutathione (GS H) spectrofluorometrically with O-phthaldialdehyde, MDA colorimetrically wi th N-methyl-2-phenylindole, and taurine by highperformance liquid chromatog raphy. Free cytosolic NAD(+)/NADH and NADP(+)/NADPH ratios were calculated from the lactate dehydrogenase and malic enzyme systems. RESULTS. Sorbitol pathway metabolites and MDA were increased, and GSH and t aurine levels were reduced in diabetic rats versus controls. The profile of glycolytic intermediates (an increase in glucose 6-phosphate, no change in fructose 6-phosphate and fructose 1,6-diphosphate, an increase in dihydrox yacetone phosphate, a decrease in 5-phosphoglycerate, phosphoenolpyruvate, and pyruvate, and no change in lactate), and a 9.2-fold increase in alpha-g lycerophosphate suggest diabetes-induced inhibition of glycolysis. Free cyt osolic NAD(+)/NADH: ratios, ATP levels, ATP/ADP, and adenylate charge were reduced, whereas free cytosolic NADP+/NADPH ratios were elevated. Lens taur ine levels in diabetic rats were not: affected by supplementation with 1% t aurine. With 5% taurine supplementation, they were increased approximately 2.2-fold higher than those in untreated diabetics but remained 3.4-fold low er than in controls. Lens GSH levels were similar in diabetic rats fed unsu pplemented and 5% taurine-supplemented diets, whereas GSSG and MDA levels a nd GSSG/GSH ratios were reduced by 5% taurine supplementation. The decrease in free cytosolic NAD(+)/NADH, ATP/ADP, and adenylate energy charge were a meliorated by 5% taurine supplementation, whereas accumulation of sorbitol pathway intermediates, depletion of myo-inositol, inhibition of glycolysis, a decrease in ATP and total adenine nucleotide, and an increase in free cy tosolic NADP(+)/NADPH were not prevented. CONCLUSIONS. Dietary taurine supplementation ameliorates MDA levels, GSSG/G SH, and NAD(+)/ NADH and fails to prevent the osmotically mediated depletio n of GSH and taurine and the decrease in glucose utilization and ATP levels in diabetic precataractous lens. Dietary taurine supplementation cannot be , regarded as an alternative to aldose reductase inhibition in eliminating antioxidant and metabolic deficits contributing to diabetes-associated cata ractogenesis.