Uremia induces abnormal oxygen consumption in tubules and aggravates chronic hypoxia of the kidney via oxidative stress
| Autor: | Takahisa Kawakami, Angelica Fasching, Fredrik Palm, Fuyuhiko Nishijima, Tetsuhiro Tanaka, Lina Nordquist, Masaomi Nangaku, Toshiro Fujita, Peter Hansell |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Indoles Time Factors Physiology Ischemia medicine.disease_cause Nephrectomy Kidney Tubules Proximal Rats Sprague-Dawley chemistry.chemical_compound Oxygen Consumption Internal medicine medicine Animals Humans Enzyme Inhibitors Ouabain Uremia Kidney NADPH oxidase biology Acetophenones NADPH Oxidases Oxides Hypoxia (medical) medicine.disease Carbon Cell Hypoxia Rats Disease Models Animal Oxidative Stress medicine.anatomical_structure Endocrinology chemistry Apocynin Disease Progression biology.protein Kidney Failure Chronic Sodium-Potassium-Exchanging ATPase medicine.symptom Indican Oxidative stress Kidney disease |
| Zdroj: | American Journal of Physiology-Renal Physiology. 299:F380-F386 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00175.2010 |
| Popis: | In addition to causing uremic symptoms, uremic toxins accelerate the progression of renal failure. To elucidate the pathophysiology of uremic states, we investigated the effect of indoxyl sulfate (IS), a representative uremic toxin, on oxygen metabolism in tubular cells. We demonstrated an increase in oxygen consumption by IS in freshly isolated rat and human proximal tubules. Studies utilizing ouabain, the Na-K-ATPase inhibitor, and apocynin, the NADPH oxidase inhibitor, as well as the in vivo gene-silencing approach to knock down p22phox showed that the increase in tubular oxygen consumption by IS is dependent on Na-K-ATPase and oxidative stress. We investigated whether the enhanced oxygen consumption led to subsequent hypoxia of the kidney. An increase in serum IS concentrations in rats administered indole was associated with a decrease in renal oxygenation (8 h). The remnant kidney in rats developed hypoxia at 16 wk. Treatment of the rats with AST-120, an oral adsorbent that removes uremic toxins, reduced serum IS levels and improved oxygenation of the kidney. Amelioration of hypoxia in the remnant kidney was associated with better renal functions and less histological injury. Reduction of serum IS levels also led to a decrease in oxidative stress in the kidney. Our ex vivo and in vivo studies implicated that uremic states may deteriorate renal dysfunction via dysregulating oxygen metabolism in tubular cells. The abnormal oxygen metabolism in tubular cells by uremic toxins was, at least in part, mediated by oxidative stress. |
| Databáze: | OpenAIRE |
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