Preventive Effect of SA13353, a Novel Transient Receptor Potential Vanilloid 1 Agonist, on Ischemia/Reperfusion-Induced Renal Injury in Rats
| Autor: | Kyoko Ueda, Masanori Takaoka, Hiroyuki Aono, Yasuo Matsumura, Fumio Tsuji, Tomoko Hirata, Kenji Ueda, Masaaki Murai |
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| Rok vydání: | 2015 |
| Předmět: |
Agonist
Kidney medicine.drug_class business.industry medicine.medical_treatment Ischemia Resiniferatoxin TRPV1 Acute kidney injury Renal function General Medicine Pharmacology urologic and male genital diseases medicine.disease Nephrectomy chemistry.chemical_compound medicine.anatomical_structure chemistry Anesthesia medicine business |
| Zdroj: | Advances in Pharmacology and Pharmacy. 3:30-42 |
| ISSN: | 2332-0044 2332-0036 |
| DOI: | 10.13189/app.2015.030202 |
| Popis: | Tumor necrosis factor (TNF)-α plays a crucial role in the pathogenesis of ischemia/reperfusion-induced renal injury. We demonstrated recently that the preischemic treatment with resiniferatoxin, a transient receptor potential vanilloid 1 (TRPV1) agonist, attenuates renal TNF-α mRNA expression, and improves ischemia/reperfusion-induced renal injury in rats. In the present study, we investigated effects of treatment with SA13353, a novel orally active TRPV1 agonist, on ischemia/reperfusion-induced renal injury in rats. Ischemic acute kidney injury (AKI) was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in vehicle-treated AKI rats markedly decreased at 24 h after reperfusion. Treatment with SA13353 (3, 10, and 30 mg/kg, p.o.) 30 min before ischemia dose-dependently attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of AKI rats revealed severe renal damage, which were significantly suppressed by the SA13353 treatment. In renal tissues exposed to ischemia/reperfusion, TNF-α and cytokine-induced neutrophil chemoattractant-1 mRNA expressions were augmented, but these alterations were attenuated by the treatment with SA13353. On the other hand, ischemia/reperfusion-enhanced renal interleukin-10 mRNA expression and its plasma concentration were further augmented by SA13353 treatment. These results demonstrate that the orally active TRPV1 agonist SA13353 prevents the ischemia/reperfusion-induced AKI. This renoprotective effects seem to be closely related to the inhibition of inflammatory response via TRPV1 activation. |
| Databáze: | OpenAIRE |
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