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

Feb 19, 2021

Contributor: Diva de Aguiar Magalhães,Jalles Arruda Batista,Stefany Guimarães Sousa,Jayro Dos Santos Ferreira,Lauanda da Rocha Rodrigues,Cynthia Maria Carvalho Pereira,José Victor do Nascimento Lima,Ieda Figueira de Albuquerque,Nayonara Lanara Sousa Dutra Bezerra,Carlos Eduardo da Silva Monteiro,Alvaro Xavier Franco,Humberto Barbosa da Costa Filho,Francisco Cleber Silva Ferreira,Alexandre Havt,David Di Lenardo,Daniel Fernando Pereira Vasconcelos,Jefferson Soares de Oliveira,Pedro Marcos Gomes Soares,André Luiz Dos Reis Barbosa

The aim of the present study was to investigate the anti-inflammatory response mediated of the M1 muscarinic acetylcholine receptor (mAChR) during experimental colitis.
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/NO), 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.
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.
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.

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About The Expert

Diva de Aguiar Magalhães

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil.

Jalles Arruda Batista

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil.

Stefany Guimarães Sousa

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil; The Northeast Biotechnology Network, Federal University of Piauí, Teresina, Brazil.

Jayro Dos Santos Ferreira

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil.

Lauanda da Rocha Rodrigues

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil.

Cynthia Maria Carvalho Pereira

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil.

José Victor do Nascimento Lima

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil.

Ieda Figueira de Albuquerque

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil.

Nayonara Lanara Sousa Dutra Bezerra

Laboratory of Experimental Physiopharmacology, LAFFEX, Federal University of Piauí, Parnaíba, Brazil.

Carlos Eduardo da Silva Monteiro

Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil.

Alvaro Xavier Franco

Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil.

Humberto Barbosa da Costa Filho

Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil.

Francisco Cleber Silva Ferreira

Laboratory of Molecular Toxinology, LTM, Federal University of Ceará, Fortaleza, CE, Brazil.

Alexandre Havt

Laboratory of Molecular Toxinology, LTM, Federal University of Ceará, Fortaleza, CE, Brazil.

David Di Lenardo

Laboratory of Analysis and Histological Processing, LAPHIS, Department of Biomedicine, Federal University of Piauí, Parnaíba, Brazil.

Daniel Fernando Pereira Vasconcelos

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.

Jefferson Soares de Oliveira

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.

Pedro Marcos Gomes Soares

Laboratory of Physiopharmacology Study of Gastrointestinal Tract, LEFFAG, Federal University of Ceará, Fortaleza, Brazil.

André Luiz Dos Reis Barbosa

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.

References

PubMed