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

Obrosova, Irina G.; Cao, Xianghui; Greene, Douglas A.; Stevens, MJ

doi:10.1007/s001250051090

Cited by 73 publications

(61 citation statements)

References 44 publications

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“…The oxidative stress response of the lens is characterized by a diminishing level of GSH and reduced activities of antioxidant enzymes (35,36). The GSH concentration in the high glucose group decreased significantly compared to that in the control group as shown in previous studies (16,37). The decrease of GSH in the high glucose group is thought to be due to the faster GSH efflux under hyperosmotic conditions caused by an accumulation of sorbitol.…”

Section: Discussionmentioning

confidence: 59%

Taurine Prevents Oxidative Damage of High Glucose-Induced Cataractogenesis in Isolated Rat Lenses

Son

Kim

Kwon

2007

J Nutr Sci Vitaminol

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Summary Diabetic cataract is an ocular disease represented as blindness by lens opacification. Oxidative as well as osmotic stress caused by accumulation of polyols within the lens has been shown to be associated with glucose-induced cataractogenesis. Taurine has an antioxidant capacity and its level in diabetic cataractous lens is markedly decreased. Therefore, we investigated whether taurine is a part of antioxidative defense mechanism involved in protecting the lens against high glucose-induced oxidative stress and tissue damage. Lenses were isolated from male Sprague-Dawley rats weighing about 180-200 g and cultured in high glucose medium (55.6 m M ) for 6 d as a model of high glucose-induced cataractogenesis. To investigate the antioxidative effect of taurine, 30 m M taurine was added in normal medium for 2 d before the addition of high glucose. The culture of lenses in high glucose medium increased the weight and opacity of lenses of and the carbonylated protein level, and decreased glutathione (GSH) content. Although there were no significant effects of taurine on the weight or opacity of lenses, pretreatment of lenses with 30 m M taurine significantly reversed the level of protein carbonylation and GSH to those of controls. Therefore, taurine might spare GSH and protect the lens from oxidative stress induced by a high concentration of glucose. Key Words cataract, oxidative stress, glucose, taurine, GSH Diabetic cataract, one of the secondary complications of diabetes, is the major cause of blindness due to the opacification of the lens. The lens is the only transparent organ in the body and focuses light on the retina. The main components of the lens are about 63% of water and 35% of protein which is composed of over 90% of crystallins ( 1 ). Because the turnover rate of crystallins is very slow compared to many other organs, the reversal of protein modification by several factors is slow and it can be thought to induce cataract ( 2 ). The mechanism of cataractogenesis is not clear, but the osmotic stress and the oxidative stress have been thought of as the major causes of cataractogenesis ( 3 ). The osmotic stress by excessive accumulation of sorbitol formed from elevated glucose has been reported as the main mechanism of diabetic cataract. But several studies indicated that oxidative stress may be the major contributor to a sugar-induced cataractogenesis, which can be prevented or attenuated by antioxidants such as vitamin E ( 4 ), glutathione (GSH) ( 5 ), vitamin C ( 6 ), and Nacetylcysteine ( 7 ). It is shown that levels of major antioxidants were reduced in cataractogenesis by osmotic compensation against sorbitol accumulation ( 8 , 9 ). Along with the loss of antioxidants, the increase of glucose concentration in the lens would result in higher free radical generation and nonenzymatic glycation ( 10 , 11 ).Taurine (2-aminoethanesulfonic acid) has a sulphonic acid group, which is not found in other amino acids. Because this amino acid is not used for the synthesis of protein, it is abundant as a fre...

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Section: Discussionmentioning

confidence: 59%

Taurine Prevents Oxidative Damage of High Glucose-Induced Cataractogenesis in Isolated Rat Lenses

Son

Kim

Kwon

2007

J Nutr Sci Vitaminol

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“…A volume of 0.1 ml of 0.3 mol/l zinc sulphate, followed by an equivalent of barium hydroxide, was then added to 0.4 ml of the homogenate for protein precipitation. The samples were centrifuged at 4000´g for 10 min (Sorvall MC 12V, Newton, Conn., USA) and aliquots of the supernatant were taken for spectrofluorometric measurements of glucose, sorbitol and fructose by enzymatic procedures as described previously [46,47]. The rest of the homogenate was centifuged at 3000´g for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of a sorbitol dehydrogenase inhibitor on diabetic peripheral nerve metabolism: a prevention study

Obrosova

Fathallah

Lang³

et al. 1999

Diabetologia

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Numerous studies in experimental models of diabetes [1±5] as well as a few clinical trials [6±9] have shown a reduction of peripheral nerve conduction deficit and morphological abnormalities by structurally different aldose reductase inhibitors thus implicating increased activity of the sorbitol pathway in the pathogenesis of diabetic neuropathy. The mechanisms leading from increased sorbitol pathway activity to complex functional, metabolic and morphological changes in the peripheral nervous system in diabetes are not com- Diabetologia (1999) AbstractAims/hypothesis. Studies of the role of sorbitol dehydrogenase in nerve functional deficits induced by diabetes reported contradictory results. We evaluated whether sorbitol dehydrogenase inhibition reduces metabolic abnormalities and enhances oxidative stress characteristic of experimental diabetic neuropathy. Methods. Control and streptozotocin-diabetic rats were treated with or without sorbitol dehydrogenase inhibitor (SDI)-157 (100 mg × kg ±1 × day ±1 , in the drinking water, for 3 weeks). Sciatic nerve free mitochondrial (cristae and matrix) and cytosolic NAD + : NADH ratios were calculated from the b-hydroxybutyrate, glutamate and lactate dehydrogenase systems. Concentrations of metabolites, e. g. sorbitol pathway intermediates and variables of energy state were measured in individual nerves spectrofluorometrically by enzymatic procedures. Results. The flux through sorbitol dehydrogenase (manifested by nerve fructose concentrations) was inhibited by 53 % and 74 % in control and diabetic rats treated with SDI compared with untreated control and diabetic groups. Free NAD + :NADH ratios in mitochondrial cristae, matrix and cytosol were decreased in diabetic rats compared with controls and reduction in either of the three variables was not prevented by sorbitol dehydrogenase inhibitor. Phosphocreatine concentrations and phosphocreatine:creatine ratios were decreased in diabetic rats compared with controls and were further reduced by the inhibitor. Malondialdehyde plus 4-hydroxyalkenals concentration was increased and reduced gluthathione concentration was reduced in diabetic rats compared with the control group, and changes in both variables were further exacerbated by sorbitol dehydrogenase inhibitor. Neither NAD-redox and energy states nor lipid aldehyde and reduced gluthathione concentrations were affected by treatment with the inhibitor in control rats. Conclusion/interpretation. Inhibition of sorbitol dehydrogenase does not offer an effective approach for prevention of oxidation and metabolic imbalances in the peripheral nerve that is induced by diabetes and is adverse rather than beneficial. [Diabetologia (1999

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“…Both AR inhibitors and antioxidants exert favorable metabolic effects that are independent from the state of perfusion and oxygen supply. For example, both classes of the compounds counteract diabetes-induced inhibition of glycolysis, NAD ϩ /NADH redox imbalances, and energy failure in such nonvascular tissue as ocular lens (43,44). The role for nonvascular AR in diabetes-associated MNCV deficit is clearly illustrated by the finding of a significantly greater reduction in MNCV in both diabetic and galactosemic transgenic mice overexpressing AR specifically in the Schwann cells of peripheral nerve under the control of the rat myelin protein zero (P 0 ) promoter compared with the corresponding nontransgenic mice with normal AR content (5).…”

Section: Fig 1 Blood Glucose Concentrations In Control (Solid Blackmentioning

confidence: 99%

Role of Poly(ADP-Ribose) Polymerase Activation in Diabetic Neuropathy

et al. 2004

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Oxidative and nitrosative stress play a key role in the pathogenesis of diabetic neuropathy, but the mechanisms remain unidentified. Here we provide evidence that poly(ADP-ribose) polymerase (PARP) activation, a downstream effector of oxidant-induced DNA damage, is an obligatory step in functional and metabolic changes in the diabetic nerve. PARP-deficient (PARP ؊/؊ ) mice were protected from both diabetic and galactose-induced motor and sensory nerve conduction slowing and nerve energy failure that were clearly manifest in the wild-type (PARP ؉/؉ ) diabetic or galactose-fed mice. Two structurally unrelated PARP inhibitors, 3-aminobenzamide and 1,5-isoquinolinediol, reversed established nerve blood flow and conduction deficits and energy failure in streptozotocin-induced diabetic rats. Sciatic nerve immunohistochemistry revealed enhanced poly(ADP-ribosyl)ation in all experimental groups manifesting neuropathic changes. Poly(ADP-ribose) accumulation was localized in both endothelial and Schwann cells. Thus, the current work identifies PARP activation as an important mechanism in diabetic neuropathy and provides the first evidence for the potential therapeutic value of PARP inhibitors in this devastating complication of diabetes. Diabetes 53: 711-720, 2004 D iabetic distal symmetric sensorimotor polyneuropathy affects up to 60 -70% of diabetic patients and is the leading cause of foot ulceration and amputation (1). Improved blood glucose control reduces the risk of peripheral diabetic neuropathy (PDN), thereby implicating hyperglycemia as a leading causative factor. Diabetic hyperglycemia causes PDN via several mechanisms, among which increased aldose reductase (AR) activity (2-5), nonenzymatic glycation/glycoxidation (6,7), and activation of protein kinase C (2,8) are the best studied. All three mechanisms contribute to enhanced oxidative and nitrosative stress (4,5,7,9 -11) resulting from imbalance between production and neutralization of reactive oxygen species. Enhanced oxidative stress has been documented in peripheral nerve (4,5,8,(12)(13)(14), dorsal root and sympathetic ganglia (15), and vasculature (16,17) of the peripheral nervous system and has been implicated in neurovascular dysfunction and motor and sensory nerve conduction velocity (MNCV and SNCV) deficits, impaired neurotrophic support, nerve metabolic and signal transduction changes, and morphologic abnormalities characteristic for diabetes (4,5,12,14,16 -20). Evidence for the pathophysiologic role of reactive nitrogen species in PDN is also emerging (16,21).The question of how oxidative and nitrosative stress causes PDN remains open. We explored the role for poly(ADP-ribose) (PAR) polymerase (PARP-1; EC 2.4.2.30), a nuclear enzyme that is activated by oxidant-induced DNA single-strand breakage and transfers ADP-ribose residues from NAD ϩ to nuclear proteins (22-25). PARP-1 is present in both endothelial cells (22,23) and Schwann cells of the peripheral nerve (26). PARP-1 activation is clearly manifest in diabetes and contributes to diabetic end...

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

Cited by 73 publications

References 44 publications

Taurine Prevents Oxidative Damage of High Glucose-Induced Cataractogenesis in Isolated Rat Lenses

Taurine Prevents Oxidative Damage of High Glucose-Induced Cataractogenesis in Isolated Rat Lenses

Evaluation of a sorbitol dehydrogenase inhibitor on diabetic peripheral nerve metabolism: a prevention study

Role of Poly(ADP-Ribose) Polymerase Activation in Diabetic Neuropathy

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