Mild ischemic Injury Leads to Long-Term Alterations in the Kidney: Amelioration by Spironolactone Administration
| Autor: | Roxana Rodríguez-Romo, Jonatan Barrera-Chimal, Norma A. Bobadilla, Marta Durand, Frederic Jaisser, Juan Antonio Ortega, Rosalba Pérez-Villalva, Andrea Sánchez |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Renal Hypertrophy Ischemia Spironolactone Kidney Applied Microbiology and Biotechnology chemistry.chemical_compound Mineralocorticoid receptor Internal medicine medicine Animals Rats Wistar Aldosterone Molecular Biology Ecology Evolution Behavior and Systematics business.industry fibrosis Acute kidney injury Cell Biology medicine.disease Rats Proteinuria medicine.anatomical_structure Endocrinology acute kidney injury chemistry Reperfusion Injury business Reperfusion injury chronic kidney disease Research Paper Developmental Biology Kidney disease |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| DOI: | 10.7150/ijbs.11729 |
| Popis: | Administration of the mineralocorticoid receptor antagonist spironolactone prevents the development of chronic kidney disease (CKD) after a severe ischemic injury. However, whether brief periods of ischemia lead to CKD and whether spironolactone administration after ischemia may be a useful therapeutic strategy to prevent the gradual deterioration of structure and function remains unexplored. Nineteen male Wistar rats were divided into four groups: rats that underwent renal bilateral ischemia for 10, 20, or 45 min were compared with sham operated rats. Additionally, thirteen male Wistar rats that underwent renal bilateral ischemia for 20 min were divided into an untreated ischemic group (I) and two groups receiving spironolactone, 20 mg/kg by gavage, at either 0 (Sp0) or 1.5-h after ischemia (Sp1.5). The rats were followed up and studied after 9 months. Mild (20 min) and severe (45 min) ischemia induced a progressive increase in proteinuria at varying magnitudes, whereas minor ischemia (10 min) did not modify proteinuria. CKD induced by moderate ischemia was characterized by renal hypertrophy and tubulointerstitial fibrosis. These effects were associated with activation of the transforming growth factor β (TGFβ) signaling pathway and up-regulation of endothelin receptor A (ETA) and alpha smooth muscle actin (αSMA). Spironolactone treatment immediately or 1.5-h after the ischemic insult prevented the onset of these disorders. Our results show that moderate ischemic insult leads to long-term structural and molecular changes that may compromise renal function in later stages. Additionally, we demonstrate that spironolactone administration after mild ischemia prevents this detrimental effect. |
| Databáze: | OpenAIRE |
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