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Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats

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Abstract

Background

Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX.

Methods and results

Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5 days), MTX (n = 8), (60 mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4 days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg chitosan via oral gavage for 4 days). After 24 h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group.

Conclusion

It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Final International University, Nicosia, Cyprus

    Kani Bilginaylar

  2. Department of Biophysics, Faculty of Medicine, Near East University, Nicosia, Cyprus

    Asli Aykac

  3. Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, Nicosia, Cyprus

    Serkan Sayiner

  4. Diagnostic Laboratory, Animal Hospital, Faculty of Veterinary Medicine, Near East University, Nicosia, Cyprus

    Serkan Sayiner

  5. Department of Pathology, Faculty of Medicine, Near East University, Nicosia, Cyprus

    Hanife Özkayalar

  6. Departments of Pharmacology, Faculty of Dentistry, Near East University, Nicosia, Cyprus

    Ahmet Özer Şehirli

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  1. Kani Bilginaylar
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  2. Asli Aykac
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  5. Ahmet Özer Şehirli
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by KB, AA, SS, HO and AOŞ. The first draft of the manuscript was written by KB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Kani Bilginaylar.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Near East University Local Animal Experiments Ethics Committee on 17/04/2020 no: 2020/111.

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Bilginaylar, K., Aykac, A., Sayiner, S. et al. Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats. Mol Biol Rep 49, 3237–3245 (2022). https://doi.org/10.1007/s11033-022-07158-x

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