Copyright © 2022 The Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

¹Research Scholar, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

^{2, 3, 4}Professor, Faculty of Pharmaceutical Sciences, Lords University, Alwar, Rajasthan

Article Info:

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Article History:

Received 26 Aug 2022

Reviewed 03 Oct 2022

Accepted 24 Oct 2022

Published 15 Nov 2022

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Cite this article as:

Khan MS, Arora P, Kalra N, Arora N, In Vivo and In Vitro Animal Models for Ulcer: A Conscious Review , Journal of Drug Delivery and Therapeutics. 2022; 12(6):227-231

DOI: http://dx.doi.org/10.22270/jddt.v12i6.5690 _______________________________________________

*Address for Correspondence:

Mohd. Shahid Khan, Research Scholar, Department of Pharmacy, 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

INTRODUCTION:

An ulcer is mainly caused due to an imbalance between the acid and pepsin and/or due to the weakness of the mucosal barrier ¹. Identification and diagnosis are always of primary importance for any disease. For this reason, researchers or epidemiologists may search for miser clue. Clinical investigations seem to improve with questionnaires designed to identify successfully used methods ². However, the demography of results related to ulcers is not stable and changes from time-to-time mainly due to age differences, sex, site of the gastric lesion, blood groups, depression, and social engagement ^2–4. Even though many discoveries were made, these discoveries do have some demerits in them. With time, research findings of an ailment can become irrelevant due to ever-changing pathology. Clinical manifestations of a disease may also differ from a different population ². Factors like urbanization, climatic condition, topography, occupational behaviors, psychogenic factors, family genetics, smoking of cigarettes, alcohol consumption, and regular coffee intake contribute to peptic ulcer ^{2, 5}. Peptic ulcer remains to be the main cause of morbidity and mortality worldwide ⁶.

Plants have been played an important role in the therapy of human and animal being disease as ancient important therapeutic resources for conventional medicine ¹. Enzymes are made up of proteins that are play important role in catalyzing chemical reactions. Enzymes have been increasing the rate of reactions until they obtain the equilibrium ^2-3.

An ulcer is caused due to an imbalance between the gastric acid and pepsin enzyme ⁴. The word ulcer is taking from latin word “ulcus” which stand for sore, wound or an ulcer. The erosion generally seen on gastric/duodenal mucosa which is referred as peptic ulcer ⁵.

Recognition and diagnosis are always of important for any disease. For this purpose, scientists, academician or epidemiologists may search for squirrel clue. Clinical examinations seem to increase with opinion poll designed to identify successfully utilized methods ⁶.

However, the anthropology of results associated to ulcers is not steady and variations from time- to-time primarily due to age variations, sex, site of the gastric lesion, depression, blood groups, and social engagement ^7–9. Even if many breakthroughs were made, these inventions do have some drawbacks in them. With moment, research conclusions of an infirmity can become immaterial due to ever-altering pathology. Clinical indications of a disease can also vary from a distinct population ¹⁰.

Factors like sprawl, climatic condition, geography, working behaviors, psychogenic influences, family inheritances, smoldering of cigarettes, alcohol drinking, and frequent coffee intake give to peptic ulcer Peptic ulcer stays to be the main trigger of morbidity and mortality universal ¹¹.

Various drugs and clinical processes accessible for prophylaxis, alleviation, and medication will be utilized as long as the assistance overshadows the adverse effects. Polypharmacy is also frequently applied due to the unattainability of a single drug efficient enough to revolutionize gastrointestinal (GI) ulcers. Uncovering greener or developing better drugs could help in avoiding the adverse effects of being pharmacotherapy for Gastric ulcers. Consequently, finding and confirming the efficacy of new leaders with superior safety and therapeutic possibility involves ethically permitted in-vitro and in-vivo methods.

Various in vivo and in vitro versions are accessible to assess the antiulcer activity of drugs/seeds. Though, variety of a suitable simulation has developed to be complicated as each type has significant benefits as well as shortcomings. Further data about these diverse in vivo and in vitro styles are dispersed in the narrative, literature and tricky to find. The foremost object of this review is too contemporary to the innumerable researchers involved in resonant out revisions on the gastroprotective possible of shrubs or herbal therapies, a comprehensive indication of obtainable in vivo and in vitro mockups that could be castoff for this purpose, along with the fundamental mechanisms of ulcer initiation in apiece method. Thus, it provides a broad interpretation of the matter that will help to take the most applicable standard for the validation of prevailing conventional therapies for gastric ulcers and expansion of novel flower-built drugs that could be utilized for their hindrance and alleviate.

An ulcer is definite as a disease that happens due to the collapse of the epithelial mucosal barricade of the stomach when unprotected to an additional of hydrochloric acid and pepsin enzyme ^12-13. The inequity between mucosal defense and aggressive influences also subsidize to irregularities of the gastric mucosa ¹⁴.

Pre-clinical models for the estimation of anti-ulcer agent

In any drug expansion, a pre-clinical analysis is a stage of investigation that is conducted out prior to clinical trials. The major intention and significance of pre-clinical assessment and/or examination is to accumulate data in assistance of the security of the agent underneath examination.

In-vitro: The purpose of preclinical methods for in vitro assessment of anti-ulcer agent is restricted. Literature data existing expose the usage of Indomethacin as the leading persuader for ulcer. For in vitro method, test medicines are assessed using several biological provisions.

In vivo models for estimation of anti-ulcer agents are commonly used. From the various prose surveys, various in vivo animal inducer models have been finding. A sequence of test medicines had been endangered for scientific assessment in different varieties of gnawers like mice, rat and guinea pigs.

DISCUSSION

The in vitro methods have been rarely used for investigation of anti-ulcer agents. In vitro assessment of anti-ulcer drugs is hardly used as adequate results cannot be acquired applying test-tube trials ⁷⁵. Moreover, it is not easy to stimulate the outcomes of long duration disclosure ⁷⁶. In vivo methods are generally applied, as the sickly condition in human being can be imitated using distinct animal prototypes ⁷⁶. Owing to their anatomical, physiological, and genetic similarities to humans, rodents like mice and rats are preferred among the various animal models. Maintenance and handling of rodents are easy due to their convenient smaller size ⁷⁷. Interestingly, mice share more than 98% DNA similarities with humans ⁷⁷.

CONCLUSION

Research for a prospective anti-ulcer agent involves fitting in vitro or in vivo models. The existing verbatim assessments systematically require a anthology of methods that are utilized in estimating anti-ulcer causes. With essential knowledge created easily understandable like ulcer inducer, drug and biological research vise versa animal simulation utilized, investigators of prospective anti-ulcer agents can use this review.

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Biological Preparation	Drug	Inducer Technique
Cultures of gastric cells from rats ¹⁵	Sucralfate formulations, aluminium hydroxide, potassium sucrose octasulfate heptahydrate and 5-aminosalicylic acid	Indomethacin
Gastric mucosal cells of rats ¹⁶	Sucralfate, Rebamipide, Cimetidine	Indomethacin
Human iPS cells ¹⁷	Meloxicam, Indomethacin, Ketoprofen, irsogladine, rebamipide	Indomethacin
Gastric mucosal cells of rats ¹⁸	Rebamipide	Mucin 2 assay
Rabbit gastric mucosal cells ¹⁹	Leminoprazole	Mucin 2 assay
Rat gastric epithelial cells ²⁰	Rebamipide on paracellular permeability of rat gastric epithelial cells	Indomethacin

Animal	Drug	Inducer
Rat	Garcinia indica	Histamine ^21-25
Rat	Somatostatin
Guineapig	Brompheniramine
Guineapig	Cyproheptadine HCl
Guineapig	Dimaprit
Rats	Benincasa hispida
Albino rats	Polyherbal formulation	Indomethacin ^26-31
Albino rats	Avicenna mariana
Sprague-Dawleyrats	Bauhinia purpurea leaf
Rats	Garlic
Rats	Telmisartan
Rats Rats	Rats Melatonin
Albino rats Sprague-Dawley rats , Mice	Polyherbal formulations Bauhinia purpurea Tetrahydrocoptisine Asparagus pubescens Methylene Blue Garcinia indica Hericium erinaceus Bovine Milk Nobiletin Annona muricata β-glucan Aucubin	Ethanol ^31-41
Rats Rats Rats	Polyherbal formulation Role of Leukocytes Zinc-carnosine chelate	Ischemia1reperfusion ^41-43
Rats Rats	Jasminum grandiflorum Polyalthia longifolia	Aspirin ^44-45
Rats Rats Rats Rats Rats	Quinoline-chalcone Montelukast cyproheptadineHCl and Promethazine HCl Pantoprazole	Pylorus ligation ^46-51
Rats	Madhuca indica	Naproxen ⁵²
Mice	Rebamide	Radiation ⁵³
Rats Rats Rats	Turmeric Ginger Omeprazole	H.Pylori ^54-57
Rats	Hesperidin	Acetic acid ⁵⁸
Rats	Bee venom	Acetylsalicylic acid ⁵⁹
Rats	Polyalthia longifolia	HCL ⁶⁰
Rats	HCl	Gastric distension ⁶¹
Rats Rats Rats Rats Rats Rats Rats	Montelukast Cyclodextrin Nitrous oxide synthase Mild whole-body heating Enhancing nitric oxide synthase Prostaglandin level Body Temp	Water immersion stress ^62- 65
Mice Rats Rats Rats	Thenalidine PGE1 Somatostatin Leucas aspera	Serotonin ^66-70
Rats	Rebamipide	Diethyldithiocarbamate ⁷¹
Rats Rats Rats Rats Rats	Zinc deficiency Cimetidine Pantoprazole Atropine and Antacids Omeprazole	Stress Induced ⁷²
Mice, Rats	5-lipoxygenase inhibitors and leukotrienes antagonist Misoprostol, Omeprazole	NSAIDs ⁷³
Rats	Hypolaetin-8-glucoside	Carrageenan ⁷⁴