Effects of Experimental Colitis in Rats on Incretin Levels, Inflammatory Markers, and Enteric Neuronal Function

Overview

Journal Arch Med Sci

Specialty General Medicine

Date 2021 Aug 2

PMID 34336036

Authors

Giuseppe Derosa

Pamela Maffioli

Angela DAngelo

Giovanna Cipolla

Elisabetta Moro

Francesca Crema

Affiliations

Soon will be listed here.

Abstract

Introduction: The aim of the study was to assess the effects of chronic inflammation on incretin levels, inflammatory markers, and enteric neuronal function measured in isolated preparations of smooth muscle of rat.

Material And Methods: We induced experimental colitis using 2,4-dinitrobenzenesulfonic acid (DNBS) in 17 Albino male Sprague-Dawley rats, while 16 rats were used as a control. They were housed in temperature-controlled rooms in a 12-h light/dark cycle at 22-24°C and 50 to 60% humidity. We evaluated in both inflamed and healthy rats: fasting plasma glucose concentration, fasting plasma insulin, myeloperoxidase, active glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and GLP-2 levels, adiponectin, and C-reactive protein (CRP). We also evaluated colonic longitudinal smooth muscle contractile activity.

Results: Intrarectal administration of DNBS reduced body weight gain in inflamed rats. We recorded higher levels of fasting plasma glucose, and insulin in inflamed rats. We observed higher levels of myeloperoxidase and CRP, and lower levels of ADN in inflamed rats. We recorded higher levels of GIP, GLP-1, and GLP-2 in inflamed rats compared to the healthy ones. Regarding functional response of colon intestinal smooth muscle after electrical stimulation, we recorded a lower functional response of colon intestinal smooth muscle after electrical stimulation in inflamed rats.

Conclusions: We can conclude that chronic inflammation leads to an increase of incretin levels and to a decrease of functional response of colon intestinal smooth muscle after electrical stimulation.

References

Gurung Y, Shimizu Y, Shiina T, Mahmoud M, Saito S, Takewaki T . Impairment and restoration of spontaneous contractile activity of longitudinal smooth muscles in the TNBS-inflamed hamster distal colon. Biomed Res. 2008; 28(6):301-8. DOI: 10.2220/biomedres.28.301. View

Stein J, Ries J, Barrett K . Disruption of intestinal barrier function associated with experimental colitis: possible role of mast cells. Am J Physiol. 1998; 274(1):G203-9. DOI: 10.1152/ajpgi.1998.274.1.G203. View

Vasina V, Abu-Gharbieh E, Barbara G, De Giorgio R, Colucci R, Blandizzi C . The beta3-adrenoceptor agonist SR58611A ameliorates experimental colitis in rats. Neurogastroenterol Motil. 2008; 20(9):1030-41. DOI: 10.1111/j.1365-2982.2008.01138.x. View

Sevcencu C . Electrical stimulation - an evolving concept in the treatment of colonic motor dysfunctions. Neurogastroenterol Motil. 2006; 18(11):960-70. DOI: 10.1111/j.1365-2982.2006.00832.x. View

Barbara G, Xing Z, Hogaboam C, Gauldie J, Collins S . Interleukin 10 gene transfer prevents experimental colitis in rats. Gut. 2000; 46(3):344-9. PMC: 1727851. DOI: 10.1136/gut.46.3.344. View

Stumpf C, Sheriff A, Zimmermann S, Schaefauer L, Schlundt C, Raaz D . C-reactive protein levels predict systolic heart failure and outcome in patients with first ST-elevation myocardial infarction treated with coronary angioplasty. Arch Med Sci. 2017; 13(5):1086-1093. PMC: 5575231. DOI: 10.5114/aoms.2017.69327. View

Rowland K, Brubaker P . The "cryptic" mechanism of action of glucagon-like peptide-2. Am J Physiol Gastrointest Liver Physiol. 2011; 301(1):G1-8. DOI: 10.1152/ajpgi.00039.2011. View

Olza J, Aguilera C, Gil-Campos M, Leis R, Bueno G, Martinez-Jimenez M . Myeloperoxidase is an early biomarker of inflammation and cardiovascular risk in prepubertal obese children. Diabetes Care. 2012; 35(11):2373-6. PMC: 3476926. DOI: 10.2337/dc12-0614. View

MacDonald P, El-Kholy W, Riedel M, Salapatek A, Light P, Wheeler M . The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes. 2002; 51 Suppl 3:S434-42. DOI: 10.2337/diabetes.51.2007.s434. View

10.

Wallace J, Le T, Carter L, Appleyard C, Beck P . Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid. J Pharmacol Toxicol Methods. 1995; 33(4):237-9. DOI: 10.1016/1056-8719(95)00001-x. View

11.

Sanovic S, Lamb D, Blennerhassett M . Damage to the enteric nervous system in experimental colitis. Am J Pathol. 1999; 155(4):1051-7. PMC: 1867003. DOI: 10.1016/S0002-9440(10)65207-8. View

12.

Blandizzi C, Fornai M, Colucci R, Baschiera F, Barbara G, De Giorgio R . Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by alpha2-adrenoceptors in the presence of experimental colitis. Br J Pharmacol. 2003; 139(2):309-20. PMC: 1573848. DOI: 10.1038/sj.bjp.0705249. View

13.

Lau D, Baldus S . Myeloperoxidase and its contributory role in inflammatory vascular disease. Pharmacol Ther. 2006; 111(1):16-26. DOI: 10.1016/j.pharmthera.2005.06.023. View

14.

van der Veen B, de Winther M, Heeringa P . Myeloperoxidase: molecular mechanisms of action and their relevance to human health and disease. Antioxid Redox Signal. 2009; 11(11):2899-937. DOI: 10.1089/ars.2009.2538. View

15.

Kawalec P . Indirect costs of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. A systematic review. Arch Med Sci. 2016; 12(2):295-302. PMC: 4848359. DOI: 10.5114/aoms.2016.59254. View

16.

Kahles F, Meyer C, Mollmann J, Diebold S, Findeisen H, Lebherz C . GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering. Diabetes. 2014; 63(10):3221-9. DOI: 10.2337/db14-0100. View

17.

Hawkins J, Emmel E, Feuer J, Nedelman M, Harvey C, Klein H . Protease activity in a hapten-induced model of ulcerative colitis in rats. Dig Dis Sci. 1997; 42(9):1969-80. DOI: 10.1023/a:1018887832465. View

18.

Sugiura M, Hirano K . A new colorimetric method for determination of serum glucose. Clin Chim Acta. 1977; 75(3):387-91. DOI: 10.1016/0009-8981(77)90357-6. View

19.

Wallace J, Keenan C . An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis. Am J Physiol. 1990; 258(4 Pt 1):G527-34. DOI: 10.1152/ajpgi.1990.258.4.G527. View

20.

Ando Y, Inaba M, Sakaguchi Y, Tsuda M, Quan G, Omae M . Subcutaneous adipose tissue-derived stem cells facilitate colonic mucosal recovery from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Inflamm Bowel Dis. 2008; 14(6):826-38. DOI: 10.1002/ibd.20382. View