RETRACTION: Preventive Effect of SA13353 [1-[2-(1-Adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea], a Novel Transient Receptor Potential Vanilloid 1 Agonist, on Ischemia/Reperfusion-Induced Renal Injury in Rats

Abstract

Tumor necrosis factor (TNF)-␣ 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-␣ mRNA expression and improves ischemia/reperfusion-induced renal injury in rats. In addition, we found that SA13353 [1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea], a novel orally active TRPV1 agonist, inhibits TNF-␣ production through the activation of capsaicin-sensitive afferent neurons and reduces the severity of symptoms in established rat collagen-induced arthritis. In the present study, we investigated effects of treatment with SA13353 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, neutrophil infiltration, superoxide production, TNF-␣ mRNA expression, and cytokine-induced neutrophil chemoattractant-1 mRNA expression 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.Renal ischemia, followed by reperfusion, is one of the most common causes of acute kidney injury (AKI) and places a significant burden on the health care system. AKI is caused by ischemic and nephrotoxic insults acting alone or in combination. It is associated with increased morbidity, prolonged hospitalizations, and increased mortality (Kelly and Molitoris, 2000). The renal tubules are susceptible to hypoxic injury because of a number of factors, but they are also capable of rapid regeneration and functional recovery. The molecular mechanisms underlying ischemia/reperfusion-induced renal injury are not fully understood, but it has been reported that several causal factors [e.g., tumor necrosis factor (TNF)-␣ mRNA expression, ATP depletion, enhancement of reactive oxygen species production, phospholipase activation, neutrophil infiltration, vasoactive peptides, etc.] are contributive to the pathogenesis of this renal damage (Edelstein et al.,

Capsaicin prevents degeneration of dopamine neurons by inhibiting glial activation and oxidative stress in the MPTP model of Parkinson’s disease

“…41 Moreover, SA13353 prevented ischemic injury through suppression of TNF-α messenger RNA expression. 42 Collectively, these results suggest that TRPV1 activation by CAP rescues nigrostriatal DA neurons in the MPTP-lesioned SN by reducing MPTP-induced expression of iNOS and proinflammatory cytokines.…”

N-Octanoyl dopamine transiently inhibits T cell proliferation via G1 cell-cycle arrest and inhibition of redox-dependent transcription factors

“…at least partially. explain the beneficial effect of NOD in ischemia-induced AKI [18,19]. Apart from the activation of the endocannabinoid and endovanilloid systems, it should also be noted that NADDs have anti-inflammatory properties [20,21] and as such, are gaining interest as potential therapeutics for the treatment of a variety of inflammatory diseases.…”

Palmitoylethanolamide Regulates Development of Intestinal Radiation Injury in a Mast Cell-Dependent Manner

“…Emerging evidence demonstrates protective functions for this unique receptor in vivo , such as for LPS-induced sepsis [51], ischemia/reperfusion injury [52], and experimental colitis [53]. Our laboratory has shown that sensory nerve ablation (to eliminate TRPV1 receptors) exacerbates intestinal radiation injury [34].…”