Preventive effect of TRPV1 agonists capsaicin and resiniferatoxin on ischemia/reperfusion-induced renal injury in rats.
We evaluated the effect of capsaicin, one of the transient receptor potential vanilloid receptor 1 (TRPV1) agonists, on ischemic acute renal failure (ARF) in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 minutes followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in vehicle-treated ARF rats markedly decreased at 24 hours after reperfusion. Treatment with capsaicin (3, 10, and 30 mg/kg, orally) 30 minutes before ischemia dose-dependently attenuated ischemia/reperfusion-induced renal dysfunction. In renal tissues exposed to ischemia/reperfusion, neutrophil infiltration, renal superoxide production, and renal tumor necrosis factor (TNF)-alpha mRNA expression were augmented, but these alterations were attenuated by the treatment with capsaicin. On the other hand, ischemia/reperfusion-enhanced renal interleukin (IL)-10 mRNA expression and plasma concentrations of IL-10 were augmented by treatment with capsaicin in ARF rats. In addition, resiniferatoxin (20 microg/kg, subcutaneous), a more selective and potent TRPV1 agonist, showed a renoprotective effect on ischemia/reperfusion-induced renal injury, in a qualitatively similar way to cases seen with capsaicin. These results demonstrate that TRPV1 agonists prevent ischemia/reperfusion-induced renal dysfunction. These renoprotective effects seem to be closely related to the inhibition of inflammatory response via TRPV1.
Ueda
Kyoko
K
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Tsuji
Fumio
F
Hirata
Tomoko
T
Takaoka
Masanori
M
Matsumura
Yasuo
Y
D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D050916:TRPV Cation Channels / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004224:Diterpenes; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C024353:resiniferatoxin; D002211:Capsaicin