3 rd Bandung International Teleconference on Pharmacy, Indonesia | 1 ORAL MUCOSAL ULCER INDUCTION METHODS IN RATS: A SYSTEMATIC REVIEW Review Article ERIS NURUL RAHMADHINI 1 , INDAH SUASANI WAHYUNI 2* 1 Oral Medicine Residency Program, Faculty of Dentistry, Universitas Padjadjaran, Jl. Sekeloa Selatan No. 1, Bandung-40132, West Java, Indonesia. 2 Department of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, Jl. Sekeloa Selatan No. 1, Bandung-40132, West Java, Indonesia * Corresponding author: Indah Suasani Wahyuni; * Email: indah.wahyuni@unpad.ac.id Received: 30 Aug 2023, Revised and Accepted: 30 Sep 2023 ABSTRACT Oral mucosal ulcers are a prevalent condition, but there are still limited drugs available to treat them. Varieties of induction techniques to obtain oral mucosal ulcer models in rats have frequently been used. This systematic review aimed to describe different approaches and to recommend the most effective method for oral mucosal ulcer induction methods in rats for anti-oral mucosal ulcer drug discovery. The PRISMA guidelines were used in the framework regarding this systematic review. The electronic databases PubMed, Science Direct, SCOPUS, and EBSCOhost-CINAHL Plus were used for article searching using specific keywords. The Risk of Bias Tool from Syrcle was used to undertake the evaluation of bias risk. Based on the analysis of 14 articles, the following findings were gathered: Wistar rats were frequently used mouse strains at an average of 8 w old and weighed between 120 and 300 g. Induction methods used to obtain ulcer models were acetic acid, biopsy punch, scalpel blade, thermal, and phenol. Acetic acid induction was the most commonly used compared to the other induction techniques. The ulcers were obtained by acetic acid identical to those that occur on the human oral mucosa and available at a reasonable price. However, the ulcer formation takes longer compared with biopsy punch and scalpel blade induction. The systematic review found that there are various methods for inducing oral ulcers in rats, with acetic acid being the recommended method to produce a suitable mucosal ulcer model in rats. Keywords: Induction methods, Oral mucosal ulcers, In vivo study, Rat © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2023.v15s2.01 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Oral mucosal ulcers are the most common oral cavity lesions caused by various factors [1-3]. Ulcer lesions are typically circular sores with a yellow-white appearance resulting from an epithelial defect covered by fibrin [4, 5]. Diagnosing lesions in the oral mucosa can be challenging for dentists due to the overlapping clinical and histological features among different types of ulcerated lesions. The majority of ulcerative lesions in the oral mucosa are associated with infection, immunity, trauma, or neoplastic disease [1, 6]. In addition, anti-oral mucosal ulcer drugs are still very limited in drug stores, even synthetic drugs or herbal materials. Therefore, further research is still needed regarding the drug discovery for oral mucosal ulceration therapy. Oral mucosal ulceration modeling in experimental animals was needed to conduct a good research method for drug discovery. One of which is the rat, especially white rats (Rattus norvegicus), which are the most commonly used animal models in research [7]. Rats have many advantages over other animals because of their relatively short life cycle (2-3.5 y), the large number of offspring per birth, ease of handling, larger body size compared to mice, ease of providing treatment and intervention, and less afraid of light. Rat's activity is not disturbed by the presence of humans in the vicinity, it is resistant to arsenic trioxide, has reproductive characteristics similar to other mammals, has anatomical structure, physiology, and genetics similar to humans, it is also easy to maintain under controlled environmental and sanitary conditions, as well as with special diets [7-9]. A valid experimental model is needed to evaluate pharmacological effects such as anti-oral mucosal ulcer effects, especially for new drug discovery or research. A good ulcer model is a useful tool in order to acquire a more comprehensive comprehension of the pathophysiology, wound healing, and pharmacology mechanisms of the disease, especially for anti-oral mucosal ulcer properties [10]. Therefore, several induction methods are carried out to obtain an ulcer model, such as using chemical, mechanical, or thermal agents. Because each method has several advantages and disadvantages, it is necessary to analyze and select the most appropriate method based on consideration of the availability of local sources, research objectives, hypothesis testing, or other factors related to the research questions [11]. Inexperienced researchers are likely to make mistakes in selecting test animal species, induction methods, and evaluation methods of test results. This may lead to ineffective research time and costs [12]. To the best of our knowledge, we have not been able to find a review article that discusses the various induction methods for oral mucosal ulceration, their comparison, and the most commonly performed by researchers in scientific journals, as well as analyses of their effectiveness. Therefore, this review article will discuss the induction methods of oral mucosal ulceration that are often used and considered effective, as well as the characteristics of rats as animal models for oral mucosal ulceration. Methods The Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines were followed when developing this systematic review and executing the literature search. Keywords were determined using the Population, Intervention, Comparison, and Outcome (PICO) method [13]. The populations that this systematic review covered are “Rats or Animal Studies or Animal Experimental or In vivo”; with intervention is “the creation of an oral ulcer or oral mucosal ulcer model”. Comparisons and outcomes in this review are found in the Results section. Inclusion criteria were articles published during the last 10 y (from 2013 to 2023), written in English with full text available, research study limited to in vivo studies, research conducted on rats with ulcers, and treatments done on non-keratinized mucosa. The exclusion criteria for this article were articles that are not relevant to the research question, not written in English, duplicate articles, in vitro studies, review articles, studies on animals other than rats, studies conducted on keratinized oral mucosa or oral hard tissue, studies on other than the oral mucosa, and studies on other diseases induction models such as induction for oral mucositis. PubMed, ScienceDirect, SCOPUS, and EBSCOhost-CINAHL Plus were used as electronic databases for literature searches from May to June 2023. The keywords being used were Oral Ulcer or Oral Mucosal Ulcer, and Animal Experimental or Animal Study or in vivo, and Rats. Syrcle’s Risk of Bias tool was utilized to evaluate article quality in this systematic review. There are 10 domains proposed to assess the International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 15, Special Issue 2, 2023