Thaise Boeing1,2, Marcelo Biondaro Gois3, Priscila de Souza4, Lincon Bordignon Somensi4, Débora de Mello Gonçales Sant Ana5, Luisa Mota da Silva4. 1. Pharmaceutical Sciences Graduate Program, Universidade do Vale do Itajaí, Rua Uruguai, 458, Itajaí, Santa Catarina, Brazil. tize.thaise@gmail.com. 2. School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil. tize.thaise@gmail.com. 3. Federal University of Recôncavo of Bahia and Institute of Health Sciences, Universidade Federal da Bahia, Salvador, Bahia, Brazil. 4. Pharmaceutical Sciences Graduate Program, Universidade do Vale do Itajaí, Rua Uruguai, 458, Itajaí, Santa Catarina, Brazil. 5. Department of Morphological Sciences, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
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.
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 irinotecantoxicity 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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