Protective outcomes of low-dose doxycycline on renal function of Wistar rats subjected to acute ischemia/reperfusion injury
| Autor: | Sabrina R. Gonsalez, Minolfa C. Prieto, Lucienne S. Lara, Aline Leal Cortes, Paulo A. Melo, André L.S. Santos, Lilimar S. Rioja, Simone S.C. Oliveira |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Renal function urologic and male genital diseases Kidney Article Excretion 03 medical and health sciences In vivo Internal medicine medicine Animals Rats Wistar Molecular Biology Doxycycline Proteinuria Renal ischemia Dose-Response Relationship Drug business.industry urogenital system Acute Kidney Injury medicine.disease Rats 030104 developmental biology medicine.anatomical_structure Endocrinology Cytoprotection Reperfusion Injury Molecular Medicine medicine.symptom business Reperfusion injury medicine.drug Glomerular Filtration Rate |
| Zdroj: | Biochimica et biophysica acta. Molecular basis of disease. 1864(1) |
| ISSN: | 0925-4439 |
| Popis: | Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Doxycycline (Dc) belongs to the tetracycline-class of antibiotics with demonstrated beneficial molecular effects in the brain and heart, mainly through matrix metalloproteinases inhibition (MMP). However, Dc protection of renal function has not been demonstrated. We determined whether low doses of Dc would prevent decreases in glomerular filtration rate (GFR) and maintain tubular Na+ handling in Wistar rats subjected to kidney I/R. Male Wistar rats underwent bilateral kidney ischemia for 30 min followed by 24 h reperfusion (I/R). Doxycycline (1, 3, and 10 mg/kg, i.p.) was administered 2 h before surgery. Untreated I/R rats showed a 250% increase in urine volume and proteinuria, a 60% reduction in GFR, accumulation of urea-nitrogen in the blood, and a 60% decrease in the fractional Na+ excretion due to unbalanced Na+ transporter activity. Treatment with Dc 3 mg/kg maintained control levels of urine volume, proteinuria, GFR, blood urea-nitrogen, fractional Na+ excretion, and equilibrated Na+ transporter activities. The Dc protection effects on renal function were associated with kidney structure preservation and prevention of TGFβ and fibronectin deposition. In vitro, total MMP activity was augmented in I/R and inhibited by 25 and 50 μM Dc. In vivo, I/R augmented MMP-2 and -9 protein content without changing their activities. Doxycycline treatment downregulated total MMP activity and MMP-2 and -9 protein content. Our results suggest that treatment with low dose Dc protects from IRI, thereby preserving kidney function. |
| Databáze: | OpenAIRE |
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