The AGE Inhibitor Pyridoxamine Inhibits Development of Retinopathy in Experimental Diabetes
| Autor: | Alan, Stitt, Thomas A, Gardiner, Nathan L, Alderson, Paul, Canning, Norma, Frizzell, Noel, Duffy, Cliona, Boyle, Andrzej S, Januszewski, Mark, Chachich, John W, Baynes, Suzanne R, Thorpe, Nathan L, Anderson |
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| Rok vydání: | 2002 |
| Předmět: |
Glycation End Products
Advanced medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Biology Retina Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Downregulation and upregulation Glycation Internal medicine Diabetes mellitus Internal Medicine medicine Animals RNA Messenger Diabetic Retinopathy Lysine Vitamin E Retinal Vessels Retinal Diabetic retinopathy medicine.disease Capillaries Extracellular Matrix Rats B vitamins Endocrinology chemistry Female Laminin Pyridoxamine |
| Zdroj: | Diabetes. 51:2826-2832 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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-alpha-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( epsilon )-(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 beta 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. |
| Databáze: | OpenAIRE |
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