title: Analysing the effect of I1imidazoline receptor ligands on DSS-induced acute colitis in mice.
abstract: 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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Fehér
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: Viktória E
authors.initials: VE
authors.lastname: Tóth
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Khrasani
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Balogh
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Lázár
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Szentagothai Research Centre and MTA-NAP B Chronic Pain Research Group, University of Pécs, Pécs, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: Klára
authors.initials: K
authors.lastname: Gyires
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary. zadori.zoltan@med.semmelweis-univ.hu.
authors.forename: Zoltán S
authors.initials: ZS
authors.lastname: Zádori
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity*; D005260:Female; D054755:Imidazoline Receptors / Q000378:metabolism*; D048288:Imidazolines / Q000378:metabolism* / Q000627:therapeutic use*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome
chemical_list: D054755:Imidazoline Receptors; D048288:Imidazolines; D008024:Ligands; C410887:imidazoline I1 receptors; D016264:Dextran Sulfate
keywords: Colitis; Dextran sulphate sodium; Imidazoline receptor; Inflammatory bowel disease