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. 2025 May;15(5):1958-1968.
doi: 10.5455/OVJ.2025.v15.i5.10. Epub 2025 May 31.

Clinical and histopathological evaluation of 5-fluorouracil-induced oral mucositis in a rat model

Ambar Kusuma Astuti  1   2 , Samsul  3 , Melva Louisa  4 , Yuniardini Septorini Wimardhani  2 , Andi Yasmon  5 , Puspita Eka Wuyung  6   7
Affiliations

Clinical and histopathological evaluation of 5-fluorouracil-induced oral mucositis in a rat model

Ambar Kusuma Astuti et al. Open Vet J. 2025 May.

Abstract

Background: Chemotherapeutics like 5-fluorouracil (5-FU) may induce a variety of adverse effects, including oral mucositis (OM), which may necessitate treatment discontinuation in patients with cancer. Currently, only a few models of OM are available for studying many aspects of pathophysiology and treatments.

Aim: The current study examined the clinical and histological aspects of 5-fluorouracil-induced oral mucositis (5FU-OM) in rats.

Methods: We randomly divided 19 male Sprague-Dawley rats into 8 healthy rats and 11 that received a single dose of 5FU-OM. On the first day of the experiment, the 5FU-OM group was administered an intraperitoneal injection of 5-FU (150-mg/kg BW), whereas the healthy group was not administered the drug. The third day involved scratching the oral mucosa of all rats in both groups. Clinical observations included changes in body weight, food consumption, hair loss, and severity of oral lesions. At the end of the study, we collected cardiac blood and mucosal tissue samples to investigate hematological and histological alterations.

Results: Our findings demonstrated that a single intraperitoneal injection of 5-FU and mucosal irritation might result in ulcerative OM. We discovered other clinical toxicities caused by chemotherapy, such as weight loss, red lacrimation, facial edema, epistaxis, and hair loss. 5-FU also produced hematological abnormalities, including anemia and thrombocytopenia. Histopathological changes included ulceration, bleeding, vasodilation, edema, and inflammatory cell infiltration.

Conclusion: This simple rat model of OM accurately replicates the clinical and histological mucosal responses to chemotherapy, including its systemic adverse effects. Thus, it can be used in research on OM.

Keywords: 5-fluorouracil; Chemotherapy; Hematology; Inflammation; Oral mucositis.

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Conflict of interest statement

All authors declare that they have no conflicts of interest and are responsible for the content and writing of the article.

Figures

Fig. 1.
Fig. 1.. Oral mucosal scratching with an 18G needle was performed on the third day of the experiment.
Fig. 2.
Fig. 2.. Mucositis lesion clinical severity. A) Grade 0, B) Grade 1, C) Grade 2, and D) Grade 3.
Fig. 3.
Fig. 3.. (A) Percentage of body weight difference versus day 1 of the experiment in the healthy and 5-FU groups. (B) The amount of food intake in the healthy and 5-FU treated groups.
Fig. 4.
Fig. 4.. (A) Oral lesion severity at the end of the experiment (day 10). The 5-FU group exhibited a significantly higher level of lesion severity. *: p < 0.05. B, C, and D show gross toxicity in the 5-FU group in terms of facial edema and chromodacryorrhea (B & C) or epistaxis and chromodacryorrhea (D).
Fig. 5.
Fig. 5.. There were no signs of hair loss or chromodacryorrhea in the healthy rat group (A and C), whereas there were evident hair losses (B) and red lacrimal secretion in the 5-FU-treated rats (D and E).
Fig. 6.
Fig. 6.. Histopathological staining of representative healthy buccal mucosal epithelium of (A) and 5-FU-induced rat buccal mucosal epithelium (B and C) at 40× magnification. White arrow: fibroblast; yellow arrow: collagen fiber; black arrow: inflammatory cells; red arrow: erythrocyte cells; green arrow: vasodilation and edema.
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References

    1. Abdalla-Aslan R., Keegan R., Zadik Y., Yarom N., Elad S. Recent advances in cancer therapy-associated oral mucositis. Oral. Dis. (in press) 2024:1–16. doi: 10.1111/odi.14999. - DOI - PubMed
    1. Bakar A., Ningrum V., Lee J., Li C.-T., Hsieh C.-W., Hong W.S., Tsai M.S. Therapeutic effect of Cinnamomum osmophloeum leaf extract on oral mucositis model rats induced by 5-fluororacil via influencing IL-1β and IL-6 levels. Processes. 2021;9:615. doi: 10.3390/pr9040615. - DOI
    1. Berger A.K., Allgäuer M., Apostolidis L., Schulze-Schleithoff A.E., Merle U., Jaeger D., Haag G.M. Cancer-related microangiopathic hemolytic anemia in patients with advanced gastric cancer: a retrospective single-center analysis. World J. Gastrointest. Oncol. 2020;12(11):1288–1295. doi: 10.4251/wjgo.v12.i11.1288. - DOI - PMC - PubMed
    1. Bertolini M., Sobue T., Thompson A., Dongari-Bagtzoglou A. Chemotherapy induces oral mucositis in mice without additional noxious stimuli. Transl. Oncol. 2017;10(4):612–620. doi: 10.1016/j.tranon.2017.05.001. - DOI - PMC - PubMed
    1. Chang C.T., Hsiang C.Y., Ho T.Y., Wu C.Z., Hong H.H., Huang Y.F. Comprehensive assessment of host responses to 5-fluorouracil-induced oral mucositis through transcriptomic analysis. PLoS One. 2015;10(8):e0135102. doi: 10.1371/journal.pone.0135102. - DOI - PMC - PubMed

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