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Blockage of the P2X7 Receptor Attenuates Harmful Changes Produced by Ischemia and Reperfusion in the Myenteric Plexus

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Abstract

Introduction

Our work analyzed the effects of a P2X7 receptor antagonist, Brilliant Blue G (BBG), on rat ileum myenteric plexus following ischemia and reperfusion (ISR) induced by 45 min of ileal artery occlusion with an atraumatic vascular clamp with 24 h (ISR 24-h group) or 14 d of reperfusion (ISR 14-d group).

Material and methods

Either BBG (50 mg/kg or 100 mg/kg, BBG50 or BBG100 groups) or saline (vehicle) was administered subcutaneously 1 h after ischemia in the ISR 24-h group or once daily for the 5 d after ischemia in the ISR 14-d group (n = 5 per group). We evaluated the neuronal density and profile area by examining the number of neutrophils in the intestinal layers, protein expression levels of the P2X7 receptor, intestinal motility and immunoreactivity for the P2X7 receptor, nitric oxide synthase, neurofilament-200, and choline acetyl transferase in myenteric neurons.

Results

The neuronal density and profile area were restored by BBG following ISR. The ischemic groups showed alterations in P2X7 receptor protein expression and the number of neutrophils in the intestine and decreased intestinal motility, all of which were recovered by BBG treatment.

Conclusion

We concluded that ISR morphologically and functionally affected the intestine and that its effects were reversed by BBG treatment, suggesting the P2X7 receptor as a therapeutic target.

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Acknowledgments

We would like to thank Rosana Prisco for the statistical analysis. These studies were supported by São Paulo Foundation Research (FAPESP Grants Nos. 2010/10510-8, 2012/00259-1, 2014/25927-2) and CAPES.

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Authors and Affiliations

  1. Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Dr. Lineu Prestes, 2415, São Paulo, CEP 05508-900, Brazil

    Kelly Palombit, Cristina Eusébio Mendes, Maria Luiza Barreto-Chaves & Patricia Castelucci

  2. Department of Morphology, Federal University of Piaui, Teresina, Brazil

    Kelly Palombit

  3. Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

    Wothan Tavares-de-Lima

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  1. Kelly Palombit
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  2. Cristina Eusébio Mendes
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Contributions

KP performed the experiments and analyzed the results. CEM helped with the immunohistochemistry study and ISR surgery. WTL helped edit the manuscript. MLBC helped in the Western blotting study. PC planned experiments, analyzed the results, and wrote and edited the manuscript.

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Correspondence to Patricia Castelucci.

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Palombit, K., Mendes, C.E., Tavares-de-Lima, W. et al. Blockage of the P2X7 Receptor Attenuates Harmful Changes Produced by Ischemia and Reperfusion in the Myenteric Plexus. Dig Dis Sci 64, 1815–1829 (2019). https://doi.org/10.1007/s10620-019-05496-8

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