In Vivo and In Vitro Animal Models for Ulcer: A Conscious Review

  • Mohd. Shahid Khan Research Scholar, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan
  • Pankaj Arora Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan
  • Naresh Kalra Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan
  • Namita Arora Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Abstract

An ulcer is definite as a disease that happens owing to subside of the epithelial mucosal wall of the stomach when unguarded to an additional of hydrochloric acid and pepsin enzyme. Research for a potential anti-ulcer agent involves appropriate in vitro or in vivo models. Due to their anatomical, physiological, and genetic similarities to humans, rodents like mice and rats are ideal among the various animal models. In vivo methods are usually applied, as the sickly condition in human being can be imitated with distinct animal prototypes. The in vitro methods have been not often used for investigation of anti-ulcer agents.


Keywords: Ulcer, Hydrochloric Acid, Anti-ulcer agents, Pepsin Enzyme

Keywords: Ulcer, Hydrochloric Acid, Anti-ulcer agents, Pepsin Enzyme

Downloads

Download data is not yet available.

Author Biographies

Mohd. Shahid Khan, Research Scholar, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Research Scholar, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Pankaj Arora, Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Naresh Kalra, Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Namita Arora, Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

References

1. Paun G. Evaluation of Geranium spp., Helleborus spp. and Hyssopus spp. polyphenolic extracts inhibitory activity against urease and α-chymotrypsin. J Enzyme Inhib Med Chem. 2013; 29(1):28-34. https://doi.org/10.3109/14756366.2012.749399
2. 2. Mosolov VL, Grigoreva, Valueva T. Plant proteinase inhibitors as multifunctional proteins (review). Appl Biochem Microbiol. 2001; 37(6): 545-551. https://doi.org/10.1023/A:1012352914306
3. 3. Bell GI. Molecular defects in diabetes mellitus. Diabetes. 1991; 40(4):413-422. https://doi.org/10.2337/diab.40.4.413
4. Hammad S et al. In vitro studies of anti-diabetic and Anti-ulcer potentials of Jatropha gossypifolia. Tropical Journal of Pharmaceutical Research. 2016; 15(1):121-125. https://doi.org/10.4314/tjpr.v15i1.17
5. Alkofahi A, Atta AH. Pharmacological screening of the anti-ulcerogenic effects of some Jordanian medicinal plants in rats. J Ethnopharmacol. 1999; 67:341-5p. https://doi.org/10.1016/S0378-8741(98)00126-3
6. Susser M. Causes of peptic ulcer: A selective epidemiologic review. J Chronic Dis. 1967; 20(6):435-56p. https://doi.org/10.1016/0021-9681(67)90015-X
7. Bonnevie O. Changing Demographies of Peptic Ulcer Disease. Digest Dis Sci. 1985; 30(11):85-145p. https://doi.org/10.1007/BF01309380
8. Fang B, Yang S, Liu H, et al. Association between depression and subsequent peptic ulcer occurrence among older people living alone: A prospective study investigating the role of change in social engagement. J Psychosom Res. 2019; 122:94-103p. https://doi.org/10.1016/j.jpsychores.2019.04.002
9. Friedman GD, Siegelaub AB, Seltzer CC. Cigarettes, Alcohol, Coffee and Peptic Ulcer. N Engl J Med. 1974; 290 (9):469-73p. https://doi.org/10.1056/NEJM197402282900901
10. Kavitt RT, Lipowska AM, Anyane-Yeboa A, et al. Diagnosis and Treatment of Peptic Ulcer Disease. Am J Med. 2019; 132(4):447-56p. https://doi.org/10.1016/j.amjmed.2018.12.009
11. Amtul M, Mohammed A, Syed H et al. Anti-Ulcer activity of medicinal plants: A review. Int. J. Pharm. Sci. Rev. 2019; 17:96-102.
12. Ramasubramaniaraja R, Babu M N, Peptic ulcer and phytochemistry: an overview, Journal of Pharmacy Research, 2011; 4:156-160.
13. Dong SXM, Chang CCY, Rowe KJ. A collection of the etiological theories, characteristics, and observations/ phenomena of peptic ulcers in existing data. Data Brief. 2018; 19: 1058-67p. 10. https://doi.org/10.1016/j.dib.2018.05.022
14. Vesely KT, Kubickkova Z, Dvorakova M, Zvolankova K. Clinical data and characteristics differentiating types of peptic ulcer. Br Med J. 1968; 9:57-68. https://doi.org/10.1136/gut.9.1.57
15. Johnson HD. Gastric Ulcer: Classification, Blood Group Characteristics, Secretion Patterns and Pathogenesis. Ann Surg. 1964; 162(6):996-1004. https://doi.org/10.1097/00000658-196512000-00005
16. Zheng H, Shah PK, Audus KL. Primary Culture of Rat Gastric Epithelial Cells as an in vitro model to Evaluate Antiulcer Agents. Pharm Res. 1994; 11(1):77-78. https://doi.org/10.1023/A:1018997711710
17. Goineau S, Castagne V. Complementarity of in vitro and in vivo models for the evaluation of gastroprotective effects of pharmacological substances. Fund Clin Pharmacol. 2016; 31(2):155-164. https://doi.org/10.1111/fcp.12248
18. Kondo S, Mizuno S, Hashita T, et al. Using human iPS cell-derived enterocytes as novel in vitro model for the evaluation of human intestinal mucosal damage. Inflamm Res. 2018; 67: 975-984. https://doi.org/10.1007/s00011-018-1193-0
19. Murakami K, Okajima K, Harada N, et al. Rebamipide prevents Indomethacin-induced gastric mucosal lesion formation by inhibiting activation of neutrophils in rats. Digest Dis Sci. 1998; 43(9): 139-142. https://doi.org/10.1016/S0016-5085(98)80960-8
20. Takahashi K, Okabe S. The cytoprotective effect of leminoprazole on Indomethacin- induced damage to rabbit gastric mucosal cells. J Pharmacol Exp Ther. 1996; 279(2): 975-182.
21. Joh T, Takezono Y, Oshima T, et al. The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells. Aliment PharmTher. 2003; 18(1): 133-138. https://doi.org/10.1046/j.1365-2036.18.s1.15.x
22. Umre R, GaneshpurkarA, Ganeshpurkar A, et al. In vitro, in vivo and in silico antiulcer activity of ferulic acid. Future J Pharm Sci. 2018; 4(2): 248- 53p. https://doi.org/10.1016/j.fjps.2018.08.001
23. Panda VS, Khambat PD. 2014. Antiulcer activity of Garciniaindica fruit rind (kokum berry) in rats. Biomed Aging Pathol. 2014; 4(4): 309-16p. https://doi.org/10.1016/j.biomag.2014.07.008
24. Meter JCV, Oleson JJ. Effect of Tagathen on Histamine-Induced Gastric Lesions in Guinea Pig. Proc Soc Exp Biol Med. 1949; 71(1): 163-5p. https://doi.org/10.3181/00379727-71-17118
25. Balibrea JL, Gomez J, Aznar J, et al.Effects of Somatostatin on Gastric Mucosal Histamine and Serotonin Content in Restrained Rats. Eur Surg Res. 1979; 11(1): 8-14p. https://doi.org/10.1159/000128047
26. Alphin RS, Ward JW. An investigation of antihistaminic activity and gastric ulceration. EurJ Pharmacol. 1969; 6(1): 61-6p. https://doi.org/10.1016/0014-2999(69)90066-1
27. Cho CH, Pfeiffer CJ. Gastrointestinal ulceration in the guinea pig in response to dimaprit, histamine, and H1- and H2- blocking agents. Dig Dis Sci. 1981; 26(4). 306-11p. https://doi.org/10.1007/BF01308370
28. Grover JK, Adiga G, Vats V, et al. Extracts of Benincasahispidaprevent development of experimental ulcers. J Ethnopharmacol. 2001; 78(2-3): 159-64p. https://doi.org/10.1016/S0378-8741(01)00334-8
29. Devaraj VC, Krishna BG. Antiulcer activity of a polyherbal formulation(PHF) from Indian medicinal plants. Chin J Nat Med. 2013; 11(2): 145-8p. https://doi.org/10.1016/S1875-5364(13)60041-2
30. El-Komy MM, Mouafi FE. Mitigating effect of Avicenna marina on indomethacin induced gastric ulcer in male albino rats. Egypt J Basic Appl Sci. 2016; 3(2): 155-63p. https://doi.org/10.1016/j.ejbas.2016.01.004
31. Zakaria ZA, Hisam EEA, Rofiee MA, et al. In vivo antiulcer activity of the aqueous extract of Bauhinia purpurea leaf. J Ethnopharmacol. 2011; 137(2): 1047-54p. https://doi.org/10.1016/j.jep.2011.07.038
32. Farrag ARH, Abdallah HMI, Khattab AR, et al. Antiulcer activity of Cyperusalternifoliusin relation to its UPLC-MS metabolite fingerprint: A mechanistic study. Phytomedicine. 2019; 62:152970. https://doi.org/10.1016/j.phymed.2019.152970
33. El-Ashmawy NE, Khedr EG, El-Bahrawy HA, et al. Gastroprotective Effect of Garlic in Indomethacin Induced Gastric Ulcer in Rats. Nutrition. 2016; 32(7-8): 849-54p. https://doi.org/10.1016/j.nut.2016.01.010
34. Hiratsuka T, Futagami S, Shindo T, et al. 2005. Rebamipide Reduces Indomethacin- Induced Gastric Injury in Mice via Down-Regulation of ICAM-1 Expression. Dig Dis Sci.2005; 50(1): 84-9p. https://doi.org/10.1007/s10620-005-2811-6
35. Soorya C, Balamurugan S, Ramya S, Neethirajan K, Kandeepan C, Jayakumararaj R. Physicochemical, ADMET and Druggable properties of Myricetin: A Key Flavonoid in Syzygium cumini that regulates metabolic inflammations. Journal of Drug Delivery and Therapeutics. 2021; 11(4):66-73. https://doi.org/10.22270/jddt.v11i4.4890
36. Fouad AA, Al-Sultan AI, Yacoubi MT, et al. Ameliorative effects of telmisartan in diabetic rats with indomethacin-induced gastric ulceration. EurJ Pharmacol. 2010; 637(1- 3): 162-70p. https://doi.org/10.1016/j.ejphar.2010.04.007
37. Bento EB, de BritoJunior FE, Oliveira DR, et al. Antiulcerogenic activity of the hydroalcoholic extract of leaves of Annonamuricata Linnaeus in mice. Saudi J Biol Sci. 2018; 25(4):609-21p. https://doi.org/10.1016/j.sjbs.2016.01.024
38. Tamaddonfarda E, Erfanparasta A, Farshid AA, et al. Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer. Life Sci. 2019; 224: 88-94p. https://doi.org/10.1016/j.lfs.2019.03.054
39. El-Moselhy MA, Abdel-Hamid NM, Abdel-Raheim SR. Gastroprotective Effect of Nicorandil in Indomethacin and Alcohol-Induced Acute Ulcers. Appl Biochem Biotechnol. 2009; 152(3): 449-59p. https://doi.org/10.1007/s12010-008-8384-z
40. Augustine BB, Pitta1 S, Lahkar M, et al. Ulcer protective effect of Leucasasperain various experimental ulcer models. Asian Pac J Trop Dis. 2014; 4(1): 395-402p. https://doi.org/10.1016/S2222-1808(14)60477-1
41. Nwafor PA, Okwasaba FK, Binda LC. Antidiarrhoeal and antiulcerogenic effects of methanolic extract of Asparagus pubescensroot in rats. J Ethnopharmacol. 2000; 72(3): 421-7p. https://doi.org/10.1016/S0378-8741(00)00261-0
42. Maity P, Bindu S, Dey S, et al. 2009. Melatonin reduces indomethacin1induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis. J Pineal Res. 2009; 46(3): 314-23p. https://doi.org/10.1111/j.1600-079X.2009.00663.x
43. Li W, Huang H, Niu X, et al. Protective effect of tetrahydrocoptisine against ethanol- induced gastric ulcer in mice. Toxicol Appl Pharmacol. 2013; 272(1): 21-9p. https://doi.org/10.1016/j.taap.2013.05.035
44. Shah DI, Santani DD, Goswami SS. A novel use of methylene blue as a pharmacological tool. JPharmacol Toxicol Methods. 2006; 54(3): 273-7p. https://doi.org/10.1016/j.vascn.2005.12.003
45. Wang XY, Yin JY, Zhao MM, et al. Gastroprotective activity of polysaccharide from Hericiumerinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation- induced gastric ulcer, and its antioxidant activities. Carbohydr Polym. 2018; 186: 100- 9p. https://doi.org/10.1016/j.carbpol.2018.01.004
46. Boligon AA, Freitas RB, Brum TF, et al. Antiulcerogenic activity of Scutiabuxifolia on gastric ulcers induced by ethanol in rats. Acta Pharm SinB. 2014; 4(5):358-67p. https://doi.org/10.1016/j.apsb.2014.05.001
47. Asmari AA,Shahrani HA, Masri NA, et al. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation. Toxicol Rep. 2015; 3:105-13p. https://doi.org/10.1016/j.toxrep.2015.11.001
48. Yoo JH, Lee JS, Lee YS, et al. Protective effect of bovine milk against HCl and ethanol- induced gastric ulcer in mice. J Dairy Sci.2018; 101(5):3758- 70p. https://doi.org/10.3168/jds.2017-13872
49. Li W, Wang X, Zhi W, et al.The gastroprotective effect of nobiletin against ethanol- induced acute gastric lesions in mice: impact on oxidative stress and inflammation.Immunopharmacol Immunotoxicol. 2017; 39(6): 354- 63p. https://doi.org/10.1080/08923973.2017.1379088
50. Oliveira AP, Souza LKM, Araujo TSL, et al. Lactobacillus reuteri DSM 17938 Protects against Gastric Damage Induced by Ethanol Administration in Mice: Role of TRPV1/Substance P Axis. Nutrients. 2019; 11(1):208. https://doi.org/10.3390/nu11010208
51. Chen H, Nie Q, Xie M, et al. Protective effects of β-glucan isolated from highland barley on ethanol-induced gastric damage in rats and its benefits to mice gut conditions. Food Res Int. 2019; 122: 157-66p. https://doi.org/10.1016/j.foodres.2019.04.011
52. Yanga Y, Ying B, Lva L, et al.Gastroprotective effect of aucubin against ethanol- induced gastric mucosal injury in mice. Life Sci. 2017; 189: 44- 51p. https://doi.org/10.1016/j.lfs.2017.09.016
53. Byeon J, Oh J, Lim JS, et al.Protective Effects of Dioscoreabatatas Flesh and Peel Extracts against Ethanol-Induced Gastric Ulcer in Mice. Nutrients. 2018; 10(11):1680. https://doi.org/10.3390/nu10111680
54. Sanchez-Mendoza ME, Lopez-Lorenzo Y, Cruz-Antonio L, et al. Gastroprotection of Calein D against Ethanol-Induced Gastric Lesions in Mice: Role of Prostaglandins, Nitric Oxide and Sulfhydryls. Molecules. 2019; 24(3):622. https://doi.org/10.3390/molecules24030622
55. Abdelwahab SI. Protective mechanism of gallic acid and its novel derivative against ethanol-induced gastric ulcerogenesis: Involvement of immunomodulation markers, Hsp70 and Bcl-2-associated X protein. Int Immunopharmacol. 2013; 16(2):296-305p. https://doi.org/10.1016/j.intimp.2013.04.005
56. Cho CH, Ogle CW. The Pharmacological Differences and Similarities between Stress- and Ethanol-Induced Gastric Mucosal Damage. Life Sci. 1992; 51(24): 1833-42p. https://doi.org/10.1016/0024-3205(92)90034-M
57. Abbas MA, Kandil YI, Disi AM, et al. Gastroprotective activity of Loranthusacaciaeflower extract in a rodent model of ethanol-induced ulcer. Appl Physiol Nutr Metab. 2019; 44(12): 1283-88p. https://doi.org/10.1139/apnm-2019-0166
58. Cheng CL,Koo MWL. Effects of Centellaasiaticaon ethanol induced gastric mucosal lesions in rats. Life Sci. 2000; 67(21): 2647-53p. https://doi.org/10.1016/S0024-3205(00)00848-1
59. Li WF, Hao DJ, Fan T, et al. Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice. Chem Biol Interact. 2014; 208: 18- 27p. https://doi.org/10.1016/j.cbi.2013.11.011
60. Bae D, Park D, Lee SH, et al. Different Antiulcer Activities of Pantoprazole in Stress, Alcohol and Pylorus Ligation-Induced Ulcer Models. Lab Anim Res. 27(1): 47-52p. https://doi.org/10.5625/lar.2011.27.1.47
61. Kandhare AD, Raygude KS, Ghosh P, et al. The ameliorative effect of fisetin, a bioflavanoid on ethanol-induced and pylorus ligation-induced gastric ulcer in rats. Int J Green Pharm. 2011; 5(3): 236-43p. https://doi.org/10.4103/0973-8258.91233
62. Park S, Hahm K, Oh T, et al. Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats. Dig Dis Sci. 2004; 49(3): 384-94p. https://doi.org/10.1023/B:DDAS.0000020490.34220.6d
63. Nanjundaiah SM, Annaiah HNM, Dharmesh SM. Gastroprotective Effect of Ginger Rhizome (Zingiberofficinale) Extract: Role of Gallic Acid and Cinnamic Acid in H+, K+-ATPase/H. pylori Inhibition and Anti-Oxidative Mechanism.Evid Based Complement Alternat Med. 2011; 2011: 249487. https://doi.org/10.1093/ecam/nep060
64. Liang J, Dou Y, Wu X, et al. Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis. Chem Biol Interact. 2018; 283:30-7p. https://doi.org/10.1016/j.cbi.2018.01.014
65. Sidahmed HMI, Vadivelu J, Loke MF, et al. 2018. Anti-ulcerogenic activity of dentatin from ClausenaexcavataBurm.f. against ethanol-induced gastric ulcer in rats: possible role of mucus and antioxidant effect. Phytomedicine. 2019; 55: 31-9. https://doi.org/10.1016/j.phymed.2018.06.036
66. Sidahmeda HMA, Hashima NM, Amira J, et al. Pyranocycloartobiloxanthone A, a novel gastroprotective compound from ArtocarpusobtususJarret, against ethanol-induced acute gastric ulcer in vivo. Phytomedicine. 2013; 20(10): 834-43p. https://doi.org/10.1016/j.phymed.2013.03.002
67. Arumugam S, Selvaraj SV, Velayutham S, et al. Evaluation of anti-ulcer activity of Samaneasaman (Jacq) merr bark on ethanol and stress induced gastric lesions in albino rats. Indian J Pharmacol. 2011; 43(5): 586-90p. https://doi.org/10.4103/0253-7613.84978
68. Muthuraman A, Sood S. Antisecretory, antioxidative and antiapoptotic effects of montelukast on pyloric ligation and water immersion stress induced peptic ulcer in rat. Prostaglandins Leukot Essent Fatty Acids. 2010; 83(1): 55-60p. https://doi.org/10.1016/j.plefa.2010.01.003
69. Rastogi L, Patnaik GK, Dikshit M. Free radicals and antioxidant status following pylorus ligation induced gastric mucosal injury in rats. Pharmacol Res. 1998; 38(2): 125-32p. https://doi.org/10.1006/phrs.1998.0343
70. Mohod SM, Bodhankar SL. Antiulcer activity of aqueous extract of leaves of MadhucaindicaJ. F. Gmel against naproxen induced gastric mucosal injury in rats. J Acute Dis. 2013; 2(2): 127-33p. https://doi.org/10.1016/S2221-6189(13)60112-2
71. Jang H, Park S, Lee J, et al. 2017. Rebamipide alleviates radiation-induced colitis through improvement of goblet cells differentiation in mice. J Gastroenterol Hepatol. 2018; 33(4):878-86p. https://doi.org/10.1111/jgh.14021
72. Rajagopal HM, Manjegowda SB, Serkada C, et al. A modified pectic polysaccharide from turmeric (Curcuma longa) with antiulcer effects via anti-secretary, mucoprotective and IL-10 mediated anti-inflammatory mechanisms. Int J Biol Macromol. 2018; 118(Pt A):864-80p. https://doi.org/10.1016/j.ijbiomac.2018.06.053
73. Konturek PC, Brzozowski T, Kania J, et al. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, accelerates gastric ulcer healing in rat. EurJ Pharmacol. 2003; 472(3): 213-20p. https://doi.org/10.1016/S0014-2999(03)01932-0
74. Biswas K, Bandyopadhyay U, Chattopadhyay I, et al. A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical. J BiolChem. 2003; 278(13): 10993- 1001p. https://doi.org/10.1074/jbc.M210328200
75. Aria I, Muramatsu M, Aihara H. Body Temperature Dependency of Gastric Regional Blood Flow, Acid Secretion and Ulcer Formation in Restraint and Water-Immersion Stressed Rats. Jpn J Pharmacol. 1986; 40(4): 501-4p. https://doi.org/10.1254/jjp.40.501
76. Itoh YH, Noguchi R. Pre-treatment with mild whole-body heating prevents gastric ulcer induced by restraint and water-immersion stress in rats. Int J Hyperthermia. 2000; 16(2): 183-91p. 106. https://doi.org/10.1080/026567300285376
77. Gati T, Guth PH. Mucosal Lesions due to Gastric Distension in the Rat. Am J Dig Dis. 1977; 22(12): 1083-90p. https://doi.org/10.1007/BF01072862
78. Pal C, Bindu S, Dey S, et al. Gallic acid prevents nonsteroidal anti1inflammatory druginduced gastropathy in rat by blocking oxidative stress and apoptosis. Free Radic Biol Med.2010; 49(2): 258-67p. https://doi.org/10.1016/j.freeradbiomed.2010.04.013
Statistics
26 Views | 4 Downloads
How to Cite
1.
Khan MS, Arora P, Kalra N, Arora N. In Vivo and In Vitro Animal Models for Ulcer: A Conscious Review. JDDT [Internet]. 15Nov.2022 [cited 9Dec.2022];12(6):227-31. Available from: https://jddtonline.info/index.php/jddt/article/view/5690