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.
About The Expert
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
References
PubMed