RCapillaries: Basement Membrane Thickening by Galactosemia Prevented with Aldose Reductase Inhibitor

Robison, W. Gerald; Kador, P.F.; Kinoshita, Jin H.

doi:10.1126/science.6612330

Cited by 257 publications

(95 citation statements)

References 13 publications

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“…Hyperglycaemiainduced mitochondrial production of ROS has been shown to induce activation of the polyol pathway [20]. Inhibition of aldose reductase activity has previously been used to inhibit glucose metabolism through the polyol pathway [21,22,23]. In the present study we used AL-1576, which in comparative studies with other aldose reductase inhibitors has been shown to be both highly potent and selective and to lack antioxidant effects [24,25].…”

Section: Discussionmentioning

confidence: 99%

Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats

et al. 2004

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Aims/hypothesis. The renal medullary region is particularly vulnerable to reduced oxygen concentration because of its low blood perfusion and high basal oxygen consumption. This study investigated renal metabolic changes in relation to the previously observed decreased oxygen tension in streptozotocin-induced diabetic rats. Methods. Blood perfusion, oxygen tension and consumption, interstitial pH, and glycolytic and purinebased metabolites were determined in the renal cortex and the medulla of non-diabetic and diabetic animals by, respectively, laser Doppler flowmetry, oxygen and pH microelectrodes, and microdialysis. The importance of increased polyol pathway activity for the observed alterations was investigated by daily treatment with the aldose reductase inhibitor AL-1576 throughout the course of diabetes.Results. The diabetes-induced decrease in renal oxygen tension, due to augmented oxygen consumption, did not result in manifest hypoxia in either the cortical or the medullary region, as evaluated by microdialysis measurements of purine-based metabolites. The profound alterations in medullary oxygen metabolism were, however, associated with an increased lactate : pyruvate ratio and a concomitantly decreased pH. Notably, the renal medullary changes in oxygen tension, oxygen consumption, lactate : pyruvate ratio and pH were preventable by inhibition of aldose reductase. Conclusions/interpretation. Substantial metabolic changes were observed in the renal medulla in diabetic animals. These disturbances seemed to be mediated by increased polyol pathway activity and could be prevented by inhibition of aldose reductase.

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Section: Discussionmentioning

confidence: 99%

Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats

et al. 2004

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“…This conclusion may in agreement with the Mizutani et al report [36] , which stated that selective Müller cell functional abnormalities in early stage of the development of diabetic retinopathy, and with the report of Dubois et al [37] , who found Müller cells death causes retinal dysplasia, photoreceptor apopotosis, and finally retinal degeneration and proliferation of the retinal pigment epithelium. Another reason that reinforce the concept of retinal degeneration by sorbitol pathway is the protection or delaying of diabetic retinopathy by using aldose reductase inhibitor (tolrestat) in diabetic rats [14] , prevention of glomerular disease by aldose reductase inhibitor (sorbinil) in diabetic rats [38] , correcting corneal endothelial changes in diabetic patient by topical aldose reductase inhibitor (placebo) in diabetic patients [39] , Prevention of diabetic complications and nerve tissue by aldose reductase inhibitors (sorbinil or sulindac) in rats lens [40] , prevention of diabetic retinopathy by aldose reductase inhibitor (sorbinil) in diabetic patients [41] , and prevention of basement membrane thickening by aldose reductase inhibitor (sorbinil) in retina of galactosemic rats [3] .…”

Section: Discussionmentioning

confidence: 99%

“…It causes an array of long-term systemic complications [1] . Among these complications is the diabetic retinopathy, which characterized by the increase in capillary permeability [2] , thickening of the basement membrane [3,4] , pericyte necrosis followed by the capillary occlusion, microaneurysms, endothelial cell proliferation, haemorrhage, oedema, neovascularization [5,6] and lately, a fibrous or glial tissue often grows with the vessels to a degree that traction and distortion of the retina may occur, producing retinal damage and retinal detachment [7] and resulting in blindness [8] .…”

Section: Introductionmentioning

confidence: 99%

Sorbitol-Induced Diabetic-Like Retinal Lesions in Rats: Microscopic Study

Ramadan¹

2007

American J. of Pharmacology and Toxicology

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Abstract:The present study investigated the sorbitol toxicity on the retinas of normal albino rats and founded by the light microscope that intra-peritoneal injection of Sorbitol (10-mg/kg-body weight per day) for 24 weeks produced similar diabetic like retinal lesions in these rats. The retinopathic effects of sorbitol injection affect retinal microvessels, pigment epithelium, neural retina and glial cells. Cytoplasmic vacuolation of the pigment epithelium and oedema of the neural retinal cells were evident. Microvascular abnormalities include thick-walled, elongated and dilated blood capillaries. The abnormal capillaries showed aneurysms and were occluded with deformed, fragmented, and adherent blood cells. Another finding was the pyknosis of glial cells. The present investigation concluded that sorbitol is toxic to the retinal tissue and it may play a role in the setup of diabetic retinopathy.

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“…These cells accumulate them because of their poor penetration across the membranes. These abnormal metabolic results have been reported to be factors responsible for diabetic complications such as cataracts (11), retinopathy (12), neuropathy (13), and nephropathy (14). Therefore, ALR2 inhibitors have considerable potential for the treatment of these diseases.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Dietary Chamomile Tea on Diabetic Complications

Kato

Minoshima

Yamamoto

et al. 2008

J. Agric. Food Chem.

162

101

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Matricaria chamomilla L., known as "chamomile", has been used as an herbal tea or supplementary food all over the world. We investigated the effects of chamomile hot water extract and its major components on the prevention of hyperglycemia and the protection or improvement of diabetic complications in diabetes mellitus. Hot water extract, esculetin (3) and quercetin (7) have been found to show moderate inhibition of sucrase with IC 50 values of 0.9 mg/mL and 72 and 71 µM, respectively. In a sucrose-loading test, the administration of esculetin (50 mg/kg body weight) fully suppressed hyperglycemia after 15 and 30 min, but the extract (500 mg/kg body weight) and quercetin (50 mg/ kg body weight) were less effective. On the other hand, a long-term feed test (21 days) using a streptozotocin-induced rat diabetes model revealed that the same doses of extract and quercetin showed significant suppression of blood glucose levels. It was also found that these samples increased the liver glycogen levels. Moreover, chamomile extract showed potent inhibition against aldose reductase (ALR2), with an IC 50 value of 16.9 µg/mL, and its components, umbelliferone (1), esculetin (3), luteolin (6), and quercetin (7), could significantly inhibit the accumulation of sorbitol in human erythrocytes. These results clearly suggested that daily consumption of chamomile tea with meals could contribute to the prevention of the progress of hyperglycemia and diabetic complications.

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RCapillaries: Basement Membrane Thickening by Galactosemia Prevented with Aldose Reductase Inhibitor

Cited by 257 publications

References 13 publications

Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats

Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats

Sorbitol-Induced Diabetic-Like Retinal Lesions in Rats: Microscopic Study

Protective Effects of Dietary Chamomile Tea on Diabetic Complications

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