4.4 Article

Irinotecan-induced intestinal mucositis in mice: a histopathological study

Journal

CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 87, Issue 3, Pages 327-336

Publisher

SPRINGER
DOI: 10.1007/s00280-020-04186-x

Keywords

Chemotherapy; Morphometric analysis; Intraepithelial lymphocytes; Enteric ganglia; Villus; Crypts

Funding

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [001]
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  3. CNPQ

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The study aimed to evaluate histopathological changes during irinotecan-induced intestinal mucositis, finding significant alterations in the tissue analysis, which contribute to establishing criteria for assessing histopathological changes and facilitating inter-study comparisons.
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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