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Advances in Pharmacology and Pharmacy Vol. 3(2), pp. 30 - 42
DOI: 10.13189/app.2015.030202
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Preventive Effect of SA13353, a Novel Transient Receptor Potential Vanilloid 1 Agonist, on Ischemia/Reperfusion-Induced Renal Injury in Rats

Kyoko Ueda ¹, Fumio Tsuji ^2,*, Tomoko Hirata ¹, Kenji Ueda ², Masaaki Murai ², Hiroyuki Aono ², Masanori Takaoka ¹, Yasuo Matsumura ^1
1 Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Japan
² Research & Development Center, Santen Pharmaceutical Co., Ltd., Japan

ABSTRACT

Tumor necrosis factor (TNF)-伪 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-伪 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-伪 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.

KEYWORDS
TRPV1, SA13353, Ischemia/Reperfusion, Acute Kidney Injury

Cite This Paper in IEEE or APA Citation Styles
(a). IEEE Format:
[1] Kyoko Ueda , Fumio Tsuji , Tomoko Hirata , Kenji Ueda , Masaaki Murai , Hiroyuki Aono , Masanori Takaoka , Yasuo Matsumura , "Preventive Effect of SA13353, a Novel Transient Receptor Potential Vanilloid 1 Agonist, on Ischemia/Reperfusion-Induced Renal Injury in Rats," Advances in Pharmacology and Pharmacy, Vol. 3, No. 2, pp. 30 - 42, 2015. DOI: 10.13189/app.2015.030202.

(b). APA Format:
Kyoko Ueda , Fumio Tsuji , Tomoko Hirata , Kenji Ueda , Masaaki Murai , Hiroyuki Aono , Masanori Takaoka , Yasuo Matsumura (2015). Preventive Effect of SA13353, a Novel Transient Receptor Potential Vanilloid 1 Agonist, on Ischemia/Reperfusion-Induced Renal Injury in Rats. Advances in Pharmacology and Pharmacy, 3(2), 30 - 42. DOI: 10.13189/app.2015.030202.