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Irinotecan-induced intestinal mucositis in mice: a histopathological study

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Abstract

Purpose

Intestinal mucositis is an important adverse effect of antineoplastic therapy, which remains without adequate treatment. The present study aimed to carry out a complete evaluation of the histopathological changes during irinotecan-induced intestinal mucositis, using the protocol most found in the pharmacological reports nowadays to better understand irinotecan toxicity and support future studies on drug discovery.

Methods

Intestinal mucositis was induced by treating swiss mice for 4 days with irinotecan (75 mg/kg, i.p.). After 72 h post irinotecan, the mice were sacrificed and the small intestine and colon were excised to performed histological analysis by stained tissue with hematoxylin/eosin (H&E).

Results

Histoarchitecture loss, villus/crypt ratio reduction, atrophy of the muscular layer, hypertrophy in the submucosal and mucous layers, ruptures in the epithelium, as well as extent cellular infiltrate and presence of micro abscesses and the fusion of the crypts were observed in the histological analysis. Moreover, duodenum and colon had increased intraepithelial lymphocytes and mitotic figures. However, submucosal ganglia were decreased in the duodenum and increased in the colon.

Conclusions

The data obtained in the present study provides new evidence that irinotecan-induced intestinal mucositis highly affects small intestine and colon, further contributing to establish criteria in light of the histopathological changes induced by irinotecan during intestinal mucositis and facilitating inter-study comparisons.

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Acknowledgements

We are grateful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Finance Code 001) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support, and to the University of Vale do Itajaí (UNIVALI) and State University of Maringá, where the study was carried out.

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Finance Code 001) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Dr. Thaise Boeing received a Postdoctoral scholarship from CNPQ.

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Authors and Affiliations

  1. Pharmaceutical Sciences Graduate Program, Universidade do Vale do Itajaí, Rua Uruguai, 458, Itajaí, Santa Catarina, Brazil

    Thaise Boeing, Priscila de Souza, Lincon Bordignon Somensi & Luisa Mota da Silva

  2. School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Thaise Boeing

  3. Federal University of Recôncavo of Bahia and Institute of Health Sciences, Universidade Federal da Bahia, Salvador, Bahia, Brazil

    Marcelo Biondaro Gois

  4. Department of Morphological Sciences, Universidade Estadual de Maringá, Maringá, Paraná, Brazil

    Débora de Mello Gonçales Sant´Ana

Authors
  1. Thaise Boeing
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  2. Marcelo Biondaro Gois
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  3. Priscila de Souza
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  4. Lincon Bordignon Somensi
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  5. Débora de Mello Gonçales Sant´Ana
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  6. Luisa Mota da Silva
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Contributions

TB, PS, and LBS performed the experimental work; MB and DMGSA performed the histological analysis; TB wrote the manuscript; LMS designed the study. All authors contributed to manuscript revision, read and approved the submitted version.

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Correspondence to Thaise Boeing.

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Boeing, T., Gois, M.B., de Souza, P. et al. Irinotecan-induced intestinal mucositis in mice: a histopathological study. Cancer Chemother Pharmacol 87, 327–336 (2021). https://doi.org/10.1007/s00280-020-04186-x

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  • DOI: https://doi.org/10.1007/s00280-020-04186-x

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