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Title:
Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina | Diabetologia
Description:
Aims/hypothesis Diabetic retinopathy is the result of increased oxidative and nitrosative stress induced by chronic hyperglycaemia, and affects the vasculature and the neuroglia. Erythropoietin is a neuroprotective and an endothelial survival factor. We assessed the effect of suberythropoietic epoetin delta doses on variables of oxidative stress in target tissues of diabetic complications and on pericyte loss in the diabetic retina. Methods We administered epoetin delta to streptozotocin-induced diabetic Wistar rats at doses of 384 IU/kg body weight once weekly or 128 IU/kg body weight three times a week. The treatment lasted for 3 months. Oxidative stress and formation of AGEs were assessed by immunoblotting, expression of Ang-2 (also known as Angpt2) by RT-PCR, activation of protein kinase B (AKT) and heat shock protein (HSP)-27 levels by immunofluorescence, and incipient retinal vascular changes by quantitative morphometry of retinal digest preparations. Results Diabetes increased variables of oxidative stress and nitrosative stress (N ε-carboxymethyl-lysine, nitrotyrosine and methylglyoxal-type AGEs) in retina, kidney and heart of diabetic rats. Epoetin delta reduced oxidative and nitrosative stress in all tissues, and AGEs in the retina. It also reduced increased retinal Ang-2 expression and pericyte loss, and ameliorated p-AKT and HSP-27 levels. Conclusions/interpretation Epoetin delta has antioxidative properties in organs affected by diabetes and may prevent incipient microvascular damage in the diabetic retina.
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Keywords {🔍}
diabetic, epoetin, delta, treatment, retina, erythropoietin, article, stress, nondiabetic, google, scholar, months, pubmed, levels, ang, retinal, cas, oxidative, pericyte, group, fig, reduced, increased, rats, highfrequency, diabetes, expression, akt, hsp, significantly, kidney, level, retinopathy, iukg, germany, vascular, endothelial, cell, cells, dose, lowfrequency, compared, loss, body, weight, formation, methylglyoxal, groups, hyperglycaemia, cml,
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o-linked n-acetylglucosamine transferase prevents hyperglycemia-induced increases rabbit anti-rat p-akt anti-epoetin delta antibodies nerve growth-factor prevents rabbit anti-rat akt hyperglycaemia-induced mitochondrial overproduction o-linked n-acetylglucosamine [14] o-linked n-acetylglucosamine glucose-driven mitochondrial overproduction common beta-subunit heteroreceptor diverse hyperglycaemia-induced abnormalities hyperglycaemia-induced oxidative stress avoiding undesired side-effects glucose-responsive gc-box 384 iu/kg body weight 128 iu/kg body weight 256 iu/kg body weight transient retinal ischemia/reperfusion epoetin delta-treated group neuroretinal programmed cell-death drug-specific immune response hyperglycaemia-induced biochemical alterations poly-adp-ribose polymerase semi-dry blotting system semi-quantitative rt-pcr streptozotocin-induced diabetic rats long-term suberythropoietic application low-frequency treatment resulted epoetin delta-treated groups 256 iu/kg thrice weekly epoetin delta-treated diabetic streptozotocin-induced diabetic rat induce glutathione peroxidase promotes endothelial cell alpha-lipoic acid dose inducing erythropoiesis secondary tissue damage housekeeping gene β-actin neuronal cell survival early diabetes-induced biochemical end-stage diabetic nephropathy endothelial survival factor related subjects oxidative stress induced oxidative stress-induced antibody formation assay erythropoietin-treated diabetic rats low-dose therapy prevents pericyte loss
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headline:Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina
description:Diabetic retinopathy is the result of increased oxidative and nitrosative stress induced by chronic hyperglycaemia, and affects the vasculature and the neuroglia. Erythropoietin is a neuroprotective and an endothelial survival factor. We assessed the effect of suberythropoietic epoetin delta doses on variables of oxidative stress in target tissues of diabetic complications and on pericyte loss in the diabetic retina. We administered epoetin delta to streptozotocin-induced diabetic Wistar rats at doses of 384 IU/kg body weight once weekly or 128 IU/kg body weight three times a week. The treatment lasted for 3 months. Oxidative stress and formation of AGEs were assessed by immunoblotting, expression of Ang-2 (also known as Angpt2) by RT-PCR, activation of protein kinase B (AKT) and heat shock protein (HSP)-27 levels by immunofluorescence, and incipient retinal vascular changes by quantitative morphometry of retinal digest preparations. Diabetes increased variables of oxidative stress and nitrosative stress (N
ε-carboxymethyl-lysine, nitrotyrosine and methylglyoxal-type AGEs) in retina, kidney and heart of diabetic rats. Epoetin delta reduced oxidative and nitrosative stress in all tissues, and AGEs in the retina. It also reduced increased retinal Ang-2 expression and pericyte loss, and ameliorated p-AKT and HSP-27 levels. Epoetin delta has antioxidative properties in organs affected by diabetes and may prevent incipient microvascular damage in the diabetic retina.
datePublished:2010-03-26T00:00:00Z
dateModified:2010-03-26T00:00:00Z
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Diabetic retinopathy
Erythropoietin
Oxidative stress
Pericyte loss
Internal Medicine
Metabolic Diseases
Human Physiology
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headline:Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina
description:Diabetic retinopathy is the result of increased oxidative and nitrosative stress induced by chronic hyperglycaemia, and affects the vasculature and the neuroglia. Erythropoietin is a neuroprotective and an endothelial survival factor. We assessed the effect of suberythropoietic epoetin delta doses on variables of oxidative stress in target tissues of diabetic complications and on pericyte loss in the diabetic retina. We administered epoetin delta to streptozotocin-induced diabetic Wistar rats at doses of 384 IU/kg body weight once weekly or 128 IU/kg body weight three times a week. The treatment lasted for 3 months. Oxidative stress and formation of AGEs were assessed by immunoblotting, expression of Ang-2 (also known as Angpt2) by RT-PCR, activation of protein kinase B (AKT) and heat shock protein (HSP)-27 levels by immunofluorescence, and incipient retinal vascular changes by quantitative morphometry of retinal digest preparations. Diabetes increased variables of oxidative stress and nitrosative stress (N
ε-carboxymethyl-lysine, nitrotyrosine and methylglyoxal-type AGEs) in retina, kidney and heart of diabetic rats. Epoetin delta reduced oxidative and nitrosative stress in all tissues, and AGEs in the retina. It also reduced increased retinal Ang-2 expression and pericyte loss, and ameliorated p-AKT and HSP-27 levels. Epoetin delta has antioxidative properties in organs affected by diabetes and may prevent incipient microvascular damage in the diabetic retina.
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Diabetic retinopathy
Erythropoietin
Oxidative stress
Pericyte loss
Internal Medicine
Metabolic Diseases
Human Physiology
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