Non-invasive biomagnetic assessment of gastrointestinal motility in a loperamide-induced constipation model

Authors

DOI:

https://doi.org/10.1590/

Keywords:

Alternating Current Biosusceptometry (ACB), Loperamide, Constipation, Gastrointestinal Transit, Colonic Motility

Abstract

Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.

Downloads

Download data is not yet available.

References

Americo MF, Marques RG, Zandoná E, Andreis UD, Stelzer, Corá LA, et al. Validation of ACB in vitro and in vivo as a biomagnetic method for measuring stomach contraction. Neurogastroenterol Motil. 2010;22(12):1340-e1374.

Américo MF, Oliveira RB, Corá LA, Marques RG, Romeiro FG, Andreis U, et al. The ACB technique: a biomagentic tool for monitoring gastrointestinal contraction directly from smooth muscle in dogs. Physiol Meas. 2009;31(2):159.

Balasuriya GK, Nugapitiya SS, Hill-Yardin EL, Bornstein JC. Nitric oxide regulates estrus cycle dependent colonic motility in mice. Front Neurosci. 2021;15.

Bongers ME, Benninga MA, Maurice-Stam H, Grootenhuis MA. Health-related quality of life in young adults with symptoms of constipation continuing from childhood into adulthood. Health Qual Life Outcomes. 2009;7(1):1-9.

Calabresi M, Quini C, Matos J, Moretto G, Americo M, Graça JRV, et al. Alternate current biosusceptometry for the assessment of gastric motility after proximal gastrectomy in rats: a feasibility study. Neurogastroenterol Motil. 2015;27(11):1613-1620.

Calabresi MF, Tanimoto A, Próspero AG, Mello FP, Soares G, Di Stasi LC, et al. Changes in colonic contractility in response to inflammatory bowel disease: Long-term assessment in a model of TNBS-induced inflammation in rats. Life Sci. 2019;236:116833.

Choi JS, Kim JW, Cho HR, Kim KY, Lee JK, Sohn JH, et al. Laxative effects of fermented rice extract in rats with loperamide‑induced constipation. Exp Ther Med. 2014;8(6):1847-1854.

Diener M, Knobloch SF, Rummel W. Action of loperamide on neuronally mediated and Ca2+-or cAMP-mediated secretion in rat colon. Eur J Pharmacol. 1988;152(3):217-225.

Eor JY, Tan PL, Lim SM, Choi DH, Yoon SM, et al. H. Laxative effect of probiotic chocolate on loperamide-induced constipation in rats. Food Res Int. 2019;116:1173-1182.

Foong D, Zhou J, Zarrouk A, Ho V, O’Connor MD. Understanding the biology of human interstitial cells of Cajal in gastrointestinal motility. Int J Mol Sci. 2020;21(12):4540.

Ford AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol. 2014;109(10):1547-1561.

Gama LA, Machado MPR, Corá LA, Beckmann APS, Alves WDL, Miranda JRA, et al. BALB/c and C57BL/6 mouse strains influence gastric function outcomes with administration of cisplatin and dexamethasone. Braz J Pharm Sci. 2023;59:e22718.

Gama LA, Rocha Machado MP, Beckmann APS, Miranda JRdA, Corá LA, Américo MF. Gastrointestinal motility and morphology in mice: Strain‐dependent differences. Neurogastroenterol Motil. 2020;32(6):e13824.

Hauschildt AT, Corá LA, Volpato GT, Sinzato YK, Damasceno DC, Américo MF. Mild diabetes: long‐term effects on gastric motility evaluated in rats. Int J Exp Pathol. 2018;99(1):29-37.

Hirst GDS, Edwards FR. Role of interstitial cells of Cajal in the control of gastric motility. J Pharmacol Sci. 2004;96(1):1-10.

Huizinga JDII. Gastric motility: lessons from mutant mice on slow waves and innervation. Am J Physiol Gastrointest Liver Physiol. 2001;281(5):G1129-G1134.

Huizinga JD, Hussain A, Chen JH. Interstitial cells of Cajal and human colon motility in health and disease. Am J Physiol Gastrointest Liver Physiol. 2021;321(5):G552-G575.

Huttunen A, Törmä P. Optimization of dual-core and microstructure fiber geometries for dispersion compensation and large mode area. Opt Express. 2005;13(2):627-635.

Jaladanki RN, Wang JY. Regulation of gastrointestinal mucosal growth. Colloq Ser Integr Syst Physiol: Mol Funct. 2011.

Kim JE, Lee YJ, Kwak MH, Ko J, Hong JT, et al. Y. Aqueous extracts of Liriope platyphylla induced significant laxative effects on loperamide-induced constipation of SD rats. BMC Complement Altern Med. 2013;13(1):1-12.

Lee HY, Kim JH, Jeung HW, Lee CU, Kim DS, et al. Effects of Ficus carica paste on loperamide-induced constipation in rats. Food Chem Toxicol. 2012;50(3-4):895-902.

Li T, Hu M, Jiang C, Zhang D, Gao M, Xia J, et al. Laxative effect and mechanism of Tiantian Capsule on loperamide-induced constipation in rats. J Ethnopharmacol. 2021;266:113411.

Liu W, Zhi A. The potential of Quercetin to protect against loperamide‐induced constipation in rats. Food Sci Nutr. 2021;9(6):3297-3307.

Ma L, Qu Z, Xu L, Han L, Han Q, He J, et al. 7, 8-dihydroxyflavone enhanced colonic cholinergic contraction and relieved loperamide-induced constipation in rats. Dig Dis Sci. 2021;66(12):4251-4262.

Narita Y, Fukumoto K, Fukunaga M, Kondo Y, Ishitsuka Y, Jono H, et al. Comparative study of constipation exacerbation by potassium binders using a loperamide-induced constipation model. Int J Mol Sci. 2020;21(7):2491.

Padmanabhan P, Grosse J, Asad ABMA, RaddaG K, Golay X. Gastrointestinal transit measurements in mice with 99m Tc-DTPA-labeled activated charcoal using NanoSPECT-CT. EJNMMI Res. 2013;3(1):60.

Podczeck F, Mitchell CL, Newton JM, Evans D, Short MB. The gastric emptying of food as measured by gamma-scintigraphy and electrical impedance tomography (EIT) and its influence on the gastric emptying of tablets of different dimensions. J Pharm Pharmacol. 2007;59(11):1527-1536.

Podczeck F, Newton JM, Yuen, KH. The description of the gastrointestinal transit of pellets assessed by gamma scintigraphy using statistical moments. Pharm Res. 1995;12(3):376-379.

Puchtler H, Waldrop FS, Meloan SN, Terry MS, Conner H. Methacarn (methanol-Carnoy) fixation: practical and theoretical considerations. Histochemie. 1970;21(2):97-116.

Romeiro FG, Corá L, De Andreis U, Américo M, Oliveira R, et al. A novel biomagnetic approach to study caecocolonic motility in humans. Neurogastroenterol Motil. 2006;18(12):1078-1083.

Senez C. Rééducation des troubles de l"alimentation et de la déglutition. De Boeck Supérieur. 2015.

Shimotoyodome A, Meguro S, Hase T, Tokimitsu I, Sakata, T. Decreased colonic mucus in rats with loperamide-induced constipation. Comp Biochem Physiol A: Mol Integr Physiol. 2000;126(2):203-212.

Soares GA, Pires DW, Pinto LA, Rodrigues GS, Prospero AG, Biasotti GGA, et al. The influence of omeprazole on the dissolution processes of pH-dependent magnetic tablets assessed by pharmacomagnetography. Pharmaceutics. 2021;13(8):1274.

Tashiro N, Budhathoki S, Ohnaka K, Toyomura K, Kono S, Tanaka M, et al. Constipation and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. Asian Pac J Cancer Prev. 2011;12(8):2025-2030.

Van der Schee E, Grashuis J. Running spectrum analysis as an aid in the representation and interpretation of electrogastrographic signals. Med Biol Eng Comput. 1987;25:57-62.

Yan S, Yue Y-Z, Wang X-P, Dong H-L, Zhen S-G, Wu B-S, et al. Aqueous extracts of Herba Cistanche promoted intestinal motility in loperamide-induced constipation rats by ameliorating the interstitial cells of cajal. Evid Based Complement Alternat Med. 2017;2017:623904.

Zhang Y, Ge T, Xiang P, Mao H, Tang S, Li A,et al. Therapeutic effect of protease-activated receptor 2 agonist SLIGRL-NH2 on loperamide-induced Sprague-Dawley rat constipation model and the related mechanism. Drug Des Devel Ther. 2018;12:2403.

Downloads

Published

2024-11-05

Issue

Section

Article

How to Cite

Non-invasive biomagnetic assessment of gastrointestinal motility in a loperamide-induced constipation model. (2024). Brazilian Journal of Pharmaceutical Sciences, 60. https://doi.org/10.1590/