Diabetes-induced changes in retinal NAD-redox status: pharmacological modulation and implications for pathogenesis of diabetic retinopathy
| Autor: | I G, Obrosova, M J, Stevens, H J, Lang |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Glutamic Acid Fructose Cell Fractionation Imidazolidines Antioxidants Piperazines Retina Diabetes Mellitus Experimental Rats Sprague-Dawley Ammonia Pyruvic Acid Animals Sorbitol Lactic Acid Enzyme Inhibitors Adrenergic alpha-Antagonists Thioctic Acid Imidazoles Prazosin NAD Mitochondria Rats Glucose Pyrimidines Ketoglutaric Acids Oxidation-Reduction |
| Zdroj: | Pharmacology. 62(3) |
| ISSN: | 0031-7012 |
| Popis: | Diabetes-induced changes in retinal metabolism and function have been linked to increased aldose reductase activity, hypoxia or 'pseudohypoxia' (increase in NADH/NAD+ attributed to increased sorbitol dehydrogenase activity). To address this controversy, we evaluated the effects of two vasoactive compounds, alpha(1)-adrenoceptor antagonist prazosin and antioxidant DL-alpha-lipoic acid, as well as sorbitol dehydrogenase inhibitor (SDI-157) and aldose reductase inhibitor (sorbinil) on retinal free mitochondrial and cytosolic NAD+/NADH ratios in streptozotocin-diabetic rats. Diabetes-induced decrease in mitochondrial and cytosolic NAD+/NADH ratios was completely or partially corrected by prazosin and DL-alpha-lipoic acid (despite the fact that prazosin did not affect and DL-alpha-lipoic acid even further increased sorbitol pathway activity) as well as by sorbinil, whereas SDI-157 was totally ineffective. Hypoxia-like metabolic changes in the diabetic retina originate from aldose reductase, but not sorbitol dehydrogenase activity. |
| Databáze: | OpenAIRE |
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