Experimental animal models for gastric ulcer / peptic ulcer: An overview
Abstract
In the present study we have discussed around sixteen different animal models used worldwide for the scientific research and new drug discovery. The main aim of the using experimental animal models in drug discovery is to establish and provide evidence for non-clinical 'proof-of-concept' for the safety, efficacy, and target of interest for specific drug molecules. Experimental preparations developed in one species for the purpose of studying phenomena occurring in another species. The use of experimental animal models serves to better understand the origins, pathology, and the overall nature of comparable diseases of humans being. Similarly, animal models perform duties for in the development of safe and effective treatments and cures of such diseases and/or associated symptoms. Experimental animal models for drug discovery and development have played a major role in the characterization of the pathophysiology of diseases and associated mechanisms of injury, drug target identification, and evaluation of novel therapeutic agents for toxicity, pharmacokinetics and pharmacodynamics activity. Through animal model researchers can perform experiments that would be impractical or ethically prohibited with humans. There are various animal models used for screening of uncountable therapeutic activities, in this review our main focus is animal models used for peptic ulcer. Peptic ulcer is one of the worldwide diseases where 10% of adults are affected by peptic ulcer once in their lifetime. The antiulcer models for drug development against gastric and duodenal ulcer studies are limited in number that has hindered the progress of targeted therapy in this field. Therefore, it is necessary to review the literature on experimental animal models that are used to screen agents with potential anti-gastric ulcer activity and describe their biochemical basis in order to facilitate their use in the development of new preventive and curative antiulcer drugs. There are many models used to induce ulcer such as pylorus ligation or it can be chemically induced by ethanol, NSAIDs (e.g. indomethacin) or many more. In this review paper, current in-vivo animal models of ulcers and the pathophysiological mechanisms underlying their induction, their drawbacks, as well as the challenges associated with their use have been discussed.
Keywords:
animal models, peptic ulcer, ethanol, NSAIDs, indomethacin, pylorus ligationDOI
https://doi.org/10.22270/jddt.v14i1.6258References
Laucirica I, Iglesias PG, Calvet X. Peptic ulcer. Medicina Clinica. 2023;169: 260-66. https://doi.org/10.1016/j.medcli.2023.05.008 PMid:37365037
Adinortey MB, Ansah C, Galyuon I, Nyarko A. In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents. Hindawi Publishing Corporation Ulcer. 2013; 2013:12. https://doi.org/10.1155/2013/796405
Monteiro KM, Spindola HM, Possenti A, Tinti SV , Ruiz ALTG, Longato GB et.al. Characterization of a refinement of the "pylorus ligation" model of rat gastric ulceration resulting in "no pain" and a more specific pharmacological response. Journal of Pharmacological and Toxicological methods. 2013; 67:121-128. https://doi.org/10.1016/j.vascn.2012.09.002 PMid:23000280
Mohd. T, SiddiquiHH, Mohd. K, Md. AAzizur R. Protective effect of hydro-alcoholic extract of Rutagraveolens Linn. leaves on indomethacin and pylorus ligation-induced gastric ulcer in rats. Journal of Ayurveda and Integrative Medicine. 2016;7:38-43. https://doi.org/10.1016/j.jaim.2015.09.002 PMid:27297508 PMCid:PMC4910575
SatapathyT, Panda PK, GoyalAK&Rath G. Evaluation of Anti-GERD Activity of Gastro Retentive Drug Delivery System of Itopride Hydrochloride. Artificial Cells, Blood Substitutes, and Biotechnology. 2010;38(4):200-207. https://doi.org/10.3109/10731191003776751 PMid:20515421
Yadin E, Thomas E. Stimulation of the lateral septum attenuates immobilization-induced stress ulcers. Physiology & Behavior. 1996;59:883-886. https://doi.org/10.1016/0031-9384(95)02184-1 PMid:8778882
Watanabe K, Matsuka N, Okazaki M, Hashimoto Y, Araki H, and Gomita Y. The Effect of Immobilization Stress on the Pharmacokinetics of Omeprazole in Rats.AcitaMedica Okayama. 2002;56( 1):19-23.
Muthuraman A, Sood S. Antisecretory, antioxidative and antiapoptotic effects of montelukast on pyloric ligation and water immersion stress induced peptic ulcer in rat. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2010;83:55-60. https://doi.org/10.1016/j.plefa.2010.01.003 PMid:20153621
Dejban P, Eslami F, Rahimi N, TakzareN, Jahansouz M, DehpourAR. Involvement of nitric oxide pathway in the anti-inflammatory effect of modafinil on indomethacin-, stress-, and ethanol -induced gastric mucosal injury in rat. European Journal of Pharmacology. 2020;887. https://doi.org/10.1016/j.ejphar.2020.173579 PMid:32950497 PMCid:PMC7495189
Guo S, Gao Q, Jiao Q, Hao W, Gao X, and Cao J. Gastric mucosal damage in water immersion stress: Mechanism and prevention with GHRP-6. World J Gastroenterol. 2012;18(24):3145-3155. https://doi.org/10.3748/wjg.v18.i24.3145 PMid:22791951 PMCid:PMC3386329
Tamaddonfard E, Erfanparast A, Farshid AA,Imani M,Navideh M, SalighedarR et.al. Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer. Life Sciences. 2019;224:88-94. https://doi.org/10.1016/j.lfs.2019.03.054 PMid:30914317
Mahmoud MF, Abdo W, Mohamed N, Drissi B, Abdelfattah M AO, Sobeh M et.al. Apple (MalusdomesticaBorkh) leaves attenuate indomethacin-induced gastric ulcer in rats. Biomedicine & Pharmacotherapy. 2023;160. https://doi.org/10.1016/j.biopha.2023.114331 PMid:36736281
Feng L,BaoT,BaiL, Mu X, Ta Na, BaoM et.al. Mongolian medicine formulae Ruda-6 alleviates indomethacin-induced gastric ulcer by regulating gut microbiome and serum metabolomics in rats. Journal of Ethnopharmacology. 2023;314. https://doi.org/10.1016/j.jep.2023.116545 PMid:37196816
da Silva DT, Rodrigues RF, Machado NM, Maurer LH, Ferreira LF, SomacalS et.al. Natural deep eutectic solvent (NADES)-based blueberry extracts protect against ethanol-induced gastric ulcer in rats. Food Research International. 2020;138(A). https://doi.org/10.1016/j.foodres.2020.109718 PMid:33292963
Zhou C, Chen J, Liu K, MaharajanK, Zhang Y, HouL at.al.Isoalantolactone protects against ethanol-induced gastric ulcer via alleviating inflammation through regulation of PI3K-Akt signaling pathway and Th17 cell differentiation. Biomedicine & Pharmacotherapy. 2023;160. https://doi.org/10.1016/j.biopha.2023.114315 PMid:36716661
Arab HH,SalamaSA, Omar HA, ArafaEl-ShaimaaA,andMaghrabi IA.Diosmin Protects against Ethanol-Induced Gastric Injury in Rats: Novel Anti-Ulcer Actions. PLoS One.2015;10(3). https://doi.org/10.1371/journal.pone.0122417 PMid:25821971 PMCid:PMC4378914
Hashim H, MughrabiFF, Mahmood A, KhalediH, Ali HM.Cytoprotective effect of benzyl N'-(5-chloro-indol-3-yl-methylidene)hydrazinecarbodithioate against ethanol-induced gastric mucosal injury in rats. Molecules 2012;17(8):9306-9320. https://doi.org/10.3390/molecules17089306 PMid:22864239 PMCid:PMC6268369
Ezer E. Effect of cytoprotective and antiulcer drugs on the healing process of subacute gastric ulcer in rat (a new model). ActaPhysiol Hung. 1989;73(2-3):233-240.
Ezer E.Novel method for producing standard subacute gastric ulcer in rats and for the quantitative evaluation of the healing process. Effect of several drugs on healing. J Pharmacol Methods. 1988;20(4):279-91. https://doi.org/10.1016/0160-5402(88)90050-2 PMid:3210680
Iwata F, JohT, Ueda F, Yokoyama Y, andItohM. Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa. Am J Physiol. 1998;275(5):G883-G888. https://doi.org/10.1152/ajpgi.1998.275.5.G883 PMid:9815015
Kuyrukluyildiz U, DelenLA, OnkD, YaziciGN, GulabogluM, Suleyman H;The effect of dexmedetomidine on gastric ischemia reperfusion injury in rats. Biochemical and histopathological evaluation. Acta Cir Bras. 2021;36(1):e360104. https://doi.org/10.1590/acb360104 PMid:33533828 PMCid:PMC7853698
OharaR, Larissa LucenaPérico, ViniciusPeixoto Rodrigues, Bueno G, Ana Caroline Zanatta,Vilegas W et.al.Terminaliacatappa L. infusion accelerates the healing process of gastric ischemia-reperfusion injury in rats. Journal of Ethnopharmacology. 2020; 256:112793. https://doi.org/10.1016/j.jep.2020.112793 PMid:32240780
Shi Z, XuF, Xia T, Bian Z, Li S. Pharmacokinetics and anti-ulcerogenic effects of Zuojin gastric floating bio-adhesive pellets in rats with acetic acid-induced gastric ulcer. Phytomedicine Plus. 2023; 3:100442. https://doi.org/10.1016/j.phyplu.2023.100442
da Silva LM, PezziniBC, SomensiLB, Mariano LNB, Mariott M, Boeing Tet.al.Hesperidin, a citrus flavanone glycoside, accelerates the gastric healing process of acetic acid-induced ulcer in rats.Chemico-Biological Interactions. 2019;308: 45-50. https://doi.org/10.1016/j.cbi.2019.05.011 PMid:31095933
Han T, Tang Y, Li J, XueB, Gong L, Li J, Yu X, Liu C. Nitric oxide donor protects against acetic acid-induced gastric ulcer in rats via S-nitrosylation of TRPV1 on vagus nerve. Sci Rep. 2017;7(1):2063. https://doi.org/10.1038/s41598-017-02275-1 PMid:28522805 PMCid:PMC5437002
Sirmagul B, Kilic FS, Batu O, Erol K. The effects of verapamil on stress- and histamine-induced gastric lesions in rats. Methods Find ExpClin Pharmacol.2004;26(10):763-67. https://doi.org/10.1358/mf.2004.26.10.872557 PMid:15672118
Troidl H, Lorenz W, Rohde H, Häfner G, Ronzheimer M. Histamine and peptic ulcer: A prospective study of mucosal histamine concentration in duodenal ulcer patients and in control subjects suffering from various gastrointestinal diseases. KlinischeWochenschrift . 1976; 54: 947-56. https://doi.org/10.1007/BF01469008 PMid:979074
Zhou Y, Wang R, Feng X, Zhao X. Preventive effect of insect tea against reserpine induced gastric ulcers in mice. Experimental and Therapeutic Medicine. 2014; 8:1318-324. https://doi.org/10.3892/etm.2014.1859 PMid:25187847 PMCid:PMC4151677
Pfeiffer CJ, Cho CH, Cheema A, Saltman D. Reserpine-induced gastric ulcers: protection by lysosomal stabilization due to zinc. European Journal of Pharmacology. 1980;61(4):347-53. https://doi.org/10.1016/0014-2999(80)90073-4 PMid:7371712
Salomone S, Caruso A, Cutuli VM, Mangano NG, Prato A, Bianchi A, et.al. Effects of adrenomedullin on the contraction of gastric arteries during reserpine-induced gastric ulcer.2003;24(1):117-22. https://doi.org/10.1016/S0196-9781(02)00283-8 PMid:12576092
Hashizume T, Aibara S, Hirokawa K, Nishida A, Ogawa H, Kasahara A. Protective effect of cetraxate, a new antiulcer drug, against serotonin-induced ulcer. Arch IntPharmacodynTher. 1979 Aug; 240(2):314-27.
Abdel-SaterKA, Abdel-Daiem WM, BakheetMd S .The gender difference of selective serotonin reuptake inhibitor, fluoxetine in adult rats with stress-induced gastric ulcer. European Journal of Pharmacology. 2012; 688:42-48. https://doi.org/10.1016/j.ejphar.2012.04.019 PMid:22546225
Ogino K, Hobara T, Kawamoto T, Kobayashi H, Iwamoto S, Oka S et.al. Mechanism of diethyldithiocarbamate-induced gastric ulcer formation in the rat. Pharmacol Toxicol. 1990; 66(2):133-37. https://doi.org/10.1111/j.1600-0773.1990.tb00719.x PMid:2156249
Takeuchi K, Nishiwaki H, Niida H, Ueshima K, Okabe S.Duodenal ulcers induced by diethyldithiocarbamate, a superoxide dismutase inhibitor, in the rat: role of antioxidative system in the pathogenesis.Jpn J Pharmacol. 1991;57(3):299-310. https://doi.org/10.1016/S0021-5198(19)39814-2 PMid:1667532
OginoK, HobaraT, Kawamoto T, Kobayashi H, Iwamoto S, Oka S, et.al.;Mechanism of Diethyldithiocarbamate-Induced Gastric Ulcer Formation in the Rat.Pharmacology & Toxicology.1990;66: 133-37. https://doi.org/10.1111/j.1600-0773.1990.tb00719.x PMid:2156249
Shah DI, SantaniDD, GoswamiSS. A novel use of methylene blue as a pharmacological tool. Journal of Pharmacological and Toxicological Methods. 2006;54:273-277. https://doi.org/10.1016/j.vascn.2005.12.003 PMid:16488629
Shivam, SachanN, Chandra P. Pharmacological Screening Techniques for Evaluation of Gastric Ulcers: Principles, Mechanism and Procedures. Int. J. Pharm. Sci. Rev. Res., 2020;65(1):224-32. https://doi.org/10.47583/ijpsrr.2020.v65i01.032
AgbajeEO, FageyinboMS, AlabiOO. Gastro-duodenal protective effect of aqueous leaf extract of Daucuscarotasativus Linn. (Apiaceae) in rats and its possible mechanism of action. The Journal of Phytopharmacology. 2017; 6(3):156-63. https://doi.org/10.31254/phyto.2017.6301
Kanemasa K, Okamura H, Kodama T, Kashima K, Ibata Y. Time course of the induction of VGF mRNA in the dorsal vagal complex in rats with cysteamine-induced peptic ulcers.Molecular Brain Research. 1995;34:309-314. https://doi.org/10.1016/0169-328X(95)00183-S PMid:8750834
Rethinavel HS, Selvaraj DB, BalakrishnanSJ , Andrews JFV , Joseph JHM , Kandasamy M. Omeprazole treatment manifests anxiolytic effects in a cysteamine hydrochloride induced mouse model of gastrointestinal disorder. Heliyon. 2022; 8:01-06. https://doi.org/10.1016/j.heliyon.2022.e09787 PMid:35800723 PMCid:PMC9253648
Hernandez DE, Adcock JW, Nemeroff CB, Arthur JP range Jr. The effect of intra cisternally administered bombesin on cysteamine-induced duodenal ulcers in rats. European Journal of Pharmacology. 1982; 84:205-209. https://doi.org/10.1016/0014-2999(82)90203-5 PMid:7173320
Takeuchi K, Okada M, Niida H, Okabe S. Healing process of duodenal ulcers induced by indomethacin plus histamine in rats. Digestion. 1989; 42(4):202-211. https://doi.org/10.1159/000199847 PMid:2806753
Takeuchi K, Furukawa O, Okada M, Okabe S. Duodenal ulcers induced by indomethacin plus histamine in the dog: involvement of the impaired duodenal alkaline secretion in their pathogenesis. Digestion 1988; 39(4):230-240. https://doi.org/10.1159/000199631 PMid:3220176
Naito Y, Yoshikawa T, Yoneta T, Yagi N, Matsuyama K, Arai M et.al. A New Gastric Ulcer Model in Rats Produced by Ferrous Iron and Ascorbic Acid Injection. Digestion 1995; 56 (6): 472-478. https://doi.org/10.1159/000201278 PMid:8536816
Grisham MB, Ritter CV , Smith BF, Lamont JT, Granger DN. Interaction between oxygen radicals and gastric mucin. American Journal of Physiology-Gastrointestinal and Liver Physiology. 1987; 253(1): G93-G96. https://doi.org/10.1152/ajpgi.1987.253.1.G93 PMid:3605340
Published
Abstract Display: 2195
PDF Downloads: 1269
PDF Downloads: 242 How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).

.