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Evaluation and vali...
Evaluation and validation of chemotherapy‐specific diarrhoea and histopathology in rats
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- Dahlgren, David (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Rosenqvist, Evelina (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Hellström, Per M., 1954- (author)
- Uppsala universitet,Gastroenterologi/hepatologi
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- Nygren, Peter (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Kullenberg, Fredrik (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Peters, Karsten (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för medicinsk cellbiologi
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- Sjöblom, Markus, 1973- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Lennernäs, Hans (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- 2022-09-30
- 2022
- English.
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In: Basic & Clinical Pharmacology & Toxicology. - : John Wiley & Sons. - 1742-7835 .- 1742-7843. ; 131:6, s. 536-546
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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