Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine

Hammes, Hans‐Peter; Bartmann, A.; Engel, Lewis L.; Wülfroth, Petra

doi:10.1007/s001250050726

Cited by 79 publications

(61 citation statements)

References 37 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment of diabetic animals with antioxidants is also known to prevent many biochemical abnormalities in the retina (29,50), although their effects on recognized pathogenic lesions in the retinal microvasculature are less well defined (17,30,51). In our study, treatment of diabetic rats with LA did not limit development of acellular strands or altered expression of ECM components.…”

Section: Discussionmentioning

confidence: 42%

The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes

et al. 2002

View full text Add to dashboard Cite

We examined the ability of pyridoxamine (PM), an inhibitor of formation of advanced glycation end products (AGEs) and lipoxidation end products (ALEs), to protect against diabetes-induced retinal vascular lesions. The effects of PM were compared with the antioxidants vitamin E (VE) and R-␣-lipoic acid (LA) in streptozotocin-induced diabetic rats. Animals were given either PM (1 g/l drinking water), VE (2,000 IU/kg diet), or LA (0.05%/kg diet). After 29 weeks of diabetes, retinas were examined for pathogenic changes, alterations in extracellular matrix (ECM) gene expression, and accumulation of the immunoreactive AGE/ALE N -(carboxymethyl)lysine (CML). Acellular capillaries were increased more than threefold, accompanied by significant upregulation of laminin immunoreactivity in the retinal microvasculature. Diabetes also increased mRNA expression for fibronectin (2-fold), collagen IV (1.6-fold), and laminin ␤ chain (2.6-fold) in untreated diabetic rats compared with nondiabetic rats. PM treatment protected against capillary drop-out and limited laminin protein upregulation and ECM mRNA expression and the increase in CML in the retinal vasculature. VE and LA failed to protect against retinal capillary closure and had inconsistent effects on diabetes-related upregulation of ECM mRNAs. These results indicate that the AGE/ALE inhibitor PM protected against a range of pathological changes in the diabetic retina and may be useful for treating diabetic retinopathy.

show abstract

Section: Discussionmentioning

confidence: 42%

The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Among the genes activated in the diabetic retina are those encoding small HSPs. For example, HSP-31 abundance was found in Müller cells of the diabetic retina, in the vicinity of capillaries of the deep plexus [11,42]. HSP-27 is a small HSP regulated by cellular stress.…”

Section: Discussionmentioning

confidence: 99%

“…Nitrotyrosine measurements have been established as a biomarker of nitrosative stress, which is implicated as a key mechanism in diabetic pathologies, affecting enzyme activities, antioxidant capacities, signal transduction and DNA integrity [10]. Target tissues of microvascular damage in diabetes differ substantially in substrates susceptible to oxidative damage, such as that caused by polyunsaturated fatty acids, and in their predisposition to inflammatory cell infiltration [11][12][13]. Vasoregression in the diabetic retina starts with pericyte loss, which is likely to involve the angiopoietin (ANG) Tie system [14].…”

Section: Introductionmentioning

confidence: 99%

Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina

et al. 2010

Self Cite

View full text Add to dashboard Cite

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 streptozotocininduced 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.

show abstract

“…However, classic antioxidants are unsuitable, because they act stoichiometrically. Several experimental and clinical trials have shown that antioxidants fail to protect from diabetic vascular damage [11][12][13]. R-(+)-α-lipoic acid is an exception, because it differs from other available antioxidants in three important aspects: (1) it distributes to mitochondria; (2) it has a very low redox potential, recycling other cellular antioxidant redox pairs (such as ascorbate); and (3) it is regenerated by hyperglycaemia-and NEFA-induced NADH (via pyruvate dehydrogenase), linking the antioxidant activity to the degree of increased metabolic flux [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis: 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. Methods: To assess the effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy, three groups of male Wistar rats were studied: nondiabetic 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. Results: After 30 weeks of diabetes, the number of acellular capillaries was significantly elevated in diabetic rats (57.1±10.6 acellular capillary segments [ac]/mm 2 of retinal area) compared with nondiabetic (19.8±5

show abstract

Antioxidant treatment of experimental diabetic retinopathy in rats with nicanartine

Cited by 79 publications

References 37 publications

The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes

The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes

Low-dose erythropoietin inhibits oxidative stress and early vascular changes in the experimental diabetic retina

Effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy

Contact Info

Product

Resources

About