ArticleBasic & clinical pharmacology & toxicology2022
Evaluation and validation of chemotherapy-specific diarrhoea and histopathology in rats.
Article in Basic & clinical pharmacology & toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 10 citations in OpenAlex.
- Characterization of hepatocellular carcinoma patient-derived organoids from patients receiving transarterial chemoembolization as a model for preclinical drug response assessment.Scientific reports · 2026Article
- Optimized rat models better mimic patients with irinotecan-induced severe diarrhea.Toxicology mechanisms and methods · 2024Article
- Melatonin mitigates chemotherapy-induced small intestinal atrophy in rats and reduces cytotoxicity in murine intestinal organoids.PloS one · 2024Article
- Evaluation and validation of chemotherapy-specific diarrhoea and histopathology in rats.Basic & clinical pharmacology & toxicology · 2022Article
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Chemotherapy-induced mucositis is characterized by diarrhoea and villous atrophy. However, it is not well-understood why diarrhoea arises, why it only occurs with some chemotherapeutics and how it is related to villus atrophy. The objectives in this study were to determine (i) the relationship between chemotherapy-induced diarrhoea and villus atrophy and to (ii) establish and validate a rat diarrhoea model with clinically relevant endpoints. Male Wistar Han IGS rats were treated with saline, doxorubicin, idarubicin, methotrexate, 5-fluorouracil, irinotecan or 5-fluorouracil+irinotecan. After 72 h, jejunal tissue was taken for morphological, apoptotic and proliferative analyses, and faecal water content and change in body weight were determined. All treatments except methotrexate caused a similar reduction (≈42%) in villus height, but none of them altered mucosal crypt cell proliferation or apoptosis. Doxorubicin, idarubicin, irinotecan and 5-fluorouracil+irinotecan caused body weight reduction, but only irinotecan and idarubicin caused diarrhoea. No direct correlation between diarrhoea and villus height or body weight loss was observed. Therefore, studies of the mechanisms for chemotherapy-induced diarrhoea should focus on functional factors. Finally, the irinotecan and idarubicin diarrhoea models established in this study will be useful in developing supportive treatments of this common and serious adverse effect in patients undergoing chemotherapy.
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