Analysing the effect of I₁ imidazoline receptor ligands on DSS-induced acute colitis in mice

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• 作者：Ágnes Fehér ; Viktória E. Tóth ; Mahmoud Al-Khrasani ; Mihály Balogh…
• 关键词：Colitis ; Inflammatory bowel disease ; Dextran sulphate sodium ; Imidazoline receptor
• 刊名：Inflammopharmacology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：25
• 期：1
• 页码：107-118
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Immunology; Rheumatology; Gastroenterology; Dermatology; Allergology;
• 出版者：Springer International Publishing
• ISSN：1568-5608
• 卷排序：25

文摘

Imidazoline receptors (IRs) have been recognized as promising targets in the treatment of numerous diseases; and moxonidine and rilmenidine, agonists of I₁-IRs, are widely used as antihypertensive agents. Some evidence suggests that IR ligands may induce anti-inflammatory effects acting on I₁-IRs or other molecular targets, which could be beneficial in patients with inflammatory bowel disease (IBD). On the other hand, several IR ligands may stimulate also alpha₂-adrenoceptors, which were earlier shown to inhibit, but in more recent studies to rather aggravate colitis. Hence, this study aimed to analyse for the first time the effect of various I₁-IR ligands on intestinal inflammation. Colitis was induced in C57BL/6 mice by adding dextran sulphate sodium (DSS) to the drinking water for 7 days. Mice were treated daily with different IR ligands: moxonidine and rilmenidine (I₁-IR agonists), AGN 192403 (highly selective I₁-IR ligand, putative antagonist), efaroxan (I₁-IR antagonist), as well as with the endogenous IR agonists agmatine and harmane. It was found that moxonidine and rilmenidine at clinically relevant doses, similarly to the other IR ligands, do not have a significant impact on the macroscopic and histological signs of DSS-evoked inflammation. Likewise, colonic myeloperoxidase and serum interleukin-6 levels remained unchanged in response to these agents. Thus, our study demonstrates that imidazoline ligands do not influence significantly the severity of DSS-colitis in mice and suggest that they probably neither affect the course of IBD in humans. However, the translational value of these findings needs to be verified with other experimental colitis models and human studies.