Journal
LIFE SCIENCES
Volume 272, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119194
Keywords
Ulcerative colitis; Pirenzepine; Oxidative stress; Inflammation
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The study revealed that the M1 muscarinic acetylcholine receptor plays an anti-inflammatory role in experimental colitis, with McN-A-343 treatment significantly reducing intestinal damage and inflammation. Blocking the M1 receptor can lead to the failure of the anti-inflammatory response.
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-beta) levels and tumor necrosis factor alpha (TNF-alpha), glutathione (GSH), malondialdehyde (MDA) and nitrate and nitrite (NO3/NO2), mRNA expression of IKK alpha, nuclear factor kappa beta (NF-kappa B) and cyclooxygenase-2 (COX-2), as well protein expression of NF-kappa B 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.
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