Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy.
Jihong Lin,Angelika Bierhaus,P Bugert,N Dietrich,Yuxi Feng,F. vom Hagen,Peter P. Nawroth,Michael Brownlee,Hans-Peter Hammes +8 more
TL;DR: R-(+)-α-lipoic acid prevents microvascular damage through normalised pathways downstream of mitochondrial overproduction of ROS, and preserves pericyte coverage of retinal capillaries, which may provide additional endothelial protection.
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Abstract: Hyperglycaemia-induced mitochondrial overproduction of reactive oxygen species (ROS) is central to the pathogenesis of endothelial damage in diabetes. R-(+)-α-lipoic acid has advantages over classic antioxidants, as it distributes to the mitochondria, is regenerated by glycolytic flux, and has a low redox potential. To assess the effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy, three groups of male Wistar rats were studied: non-diabetic controls, untreated diabetic controls, and diabetic rats treated with 60 mg/kg bodyweight R-(+)-α-lipoic acid i.p. for 30 weeks. Quantitative retinal morphometry included acellular occluded capillaries and pericyte numbers. The effects of R-(+)-α-lipoic acid on parameters of oxidative and nitrative stress, AGE and its receptor and nuclear factor kappa B (NFκB) were assessed by immunoblotting, and NFκB activation by electrophoretic mobility shift assay. Angiopoietin-2 and vascular endothelial growth factors were also determined by immunoblotting. After 30 weeks of diabetes, the number of acellular capillaries was significantly elevated in diabetic rats (57.1±10.6 acellular capillary segments [ac]/mm2 of retinal area) compared with non-diabetic (19.8±5.1 ac/mm2; p<0.001). Treatment with 60 mg/kg R-(+)-α-lipoic acid reduced the numbers by 88% (p<0.001 vs diabetic). Pericyte loss was also significantly inhibited in diabetic rats treated with R-(+)-α-lipoic acid (non-diabetic: 1,940±137 pericytes/mm2capillary area; untreated diabetic: 1,294±94 pericytes/mm2capillary area vs treated diabetic: 1,656±134 pericytes/mm2; p<0.01). R-(+)-α-lipoic acid treatment reduced oxidative stress, normalised NFκB activation and angiopoietin-2 expression, and reduced vascular endothelial growth factor in the diabetic retina by 43% (p<0.0001). R-(+)-α-lipoic acid prevents microvascular damage through normalised pathways downstream of mitochondrial overproduction of ROS, and preserves pericyte coverage of retinal capillaries, which may provide additional endothelial protection.
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Citations
Oxidative Stress and Diabetic Retinopathy
Renu A. Kowluru,Pooi-See Chan +1 more
TL;DR: Although antioxidants are being used for other chronic diseases, controlled clinical trials are warranted to investigate potential beneficial effects of antioxidants in the development of retinopathy in diabetic patients.
Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species
TL;DR: The potential usefulness and the challenges in modulating the oxidant-antioxidant balance as a potentially promising, but currently disappointing, means of improving insulin action in insulin resistance-associated conditions, leading causes of human morbidity and mortality of the authors' era are explored.
567
Diabetic Microvascular Disease: An Endocrine Society Scientific Statement.
Eugene J. Barrett,Zhenqi Liu,Mogher Khamaisi,George L. King,Ronald Klein,Barbara E.K. Klein,Timothy M. Hughes,Suzanne Craft,Barry I. Freedman,Donald W. Bowden,Aaron I. Vinik,Carolina Casellini +11 more
TL;DR: It is disappointing that microvascular complications of diabetes continue to compromise the quantity and quality of life for patients with diabetes, and by understanding and building on current research findings, new approaches for prevention and treatment that will be effective for future generations are discovered.
The effects of gold nanoparticles in wound healing with antioxidant epigallocatechin gallate and α-lipoic acid.
Jyh-Gang Leu,Siang-An Chen,Han-Min Chen,Wen-Mein Wu,Chi-Feng Hung,Yeong-Der Yao,Chi-Shun Tu,Yao-Jen Liang +7 more
TL;DR: Topically applied gold nanoparticles with epigallocatechin gallate and alpha-lipoic acid significantly accelerated mouse cutaneous wound healing through anti-inflammatory and antioxidation effects and may support future studies using other antioxidants in the treatment of cutaneous wounds.
265
Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases
TL;DR: An up-to-date review of current thinking regarding alpha-lipoic acid and its use as an antioxidant drug therapy for a myriad of diseases that could have potential benefits from its use is made.
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Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
Uk-Prospective-Diabetes-Study-Group
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TL;DR: The effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial were compared.
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