McN-A-343, a muscarinic agonist, reduces inflammation and oxidative stress in an experimental model of ulcerative colitis.

Autor: Magalhães DA; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil., Batista JA; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil., Sousa SG; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil., Ferreira JDS; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil., da Rocha Rodrigues L; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil., Pereira CMC; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil., do Nascimento Lima JV; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil., de Albuquerque IF; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil., Bezerra NLSD; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil., Monteiro CEDS; Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil., Franco AX; Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil., da Costa Filho HB; Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil., Ferreira FCS; Laboratory of Molecular Toxinology, LTM, Federal University of Ceará, Fortaleza, CE, Brazil., Havt A; Laboratory of Molecular Toxinology, LTM, Federal University of Ceará, Fortaleza, CE, Brazil., Di Lenardo D; Laboratory of Analysis and Histological Processing, LAPHIS, Department of Biomedicine, Federal University of Piauí, Parnaíba, Brazil., Vasconcelos DFP; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil; Laboratory of Analysis and Histological Processing, LAPHIS, Department of Biomedicine, Federal University of Piauí, Parnaíba, Brazil., de Oliveira JS; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil; Biochemistry Laboratory of Laticifers Plants (LABPL), Department of Biomedicine, Federal University of Piauí, Parnaíba, Brazil., Soares PMG; Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil., Barbosa ALDR; Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil. Electronic address: andreluiz@ufpi.edu.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 May 01; Vol. 272, pp. 119194. Date of Electronic Publication: 2021 Feb 18.
DOI: 10.1016/j.lfs.2021.119194
Abstrakt: Aim: The aim of the present study was to investigate the anti-inflammatory response mediated of the M1 muscarinic acetylcholine receptor (mAChR) during experimental colitis.
Material and Methods: After the induction of 6% acetic acid colitis, mice were treated with McN-A-343 0.5, 1.0, and 1.5 mg/kg or dexamethasone (DEXA, 2.0 mg/kg) or pirenzepine (PIR, 10 mg/kg; M1 mAChR antagonist). Colonic inflammation was assessed by macroscopic and microscopic lesion scores, colonic wet weight, myeloperoxidase (MPO) activity, interleukin-1 beta (IL1-β) levels and tumor necrosis factor alpha (TNF-α), glutathione (GSH), malondialdehyde (MDA) and nitrate and nitrite (NO 3 /NO 2 ), mRNA expression of IKKα, nuclear factor kappa beta (NF-kB) and cyclooxygenase-2 (COX-2), as well protein expression of NF-kB and COX-2.
Results: Treatment with McN-A-343 at a concentration of 1.5 mg/kg showed a significant reduction in intestinal damage as well as a decrease in wet weight, MPO activity, pro-inflammatory cytokine concentration, markers of oxidative stress and expression of inflammatory mediators. The action of the M1 agonist by the administration of pirenzepine, which promoted the blocking of the mAChR M1-mediated anti-inflammatory response, has also been proven.
Conclusion: The results suggest that peripheral colonic M1 mAChR is involved in reversing the pro-inflammatory effect of experimentally induced colitis, which may represent a promising therapeutic alternative for patients with ulcerative colitis.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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