Irinotecan-induced alterations in intestinal cell kinetics and extracellular matrix component expression in the dark agouti rat

Summary Chemotherapy‐induced mucositis is characterized by damage of mucous membranes throughout the alimentary tract (AT). Extracellular matrix (ECM) components play a vital role in maintaining mucosal barrier integrity by regulating cellular apoptosis, proliferation and differentiation of overlyin...

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Bibliographic Details
Published in:International journal of experimental pathology 2011-10, Vol.92 (5), p.357-365
Main Authors: Al-Dasooqi, Noor, Bowen, Joanne M., Gibson, Rachel J., Logan, Richard M., Stringer, Andrea M., Keefe, Dorothy M.
Format: Article
Language:English
Subjects:
alimentary tract
Animals
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Camptothecin - analogs & derivatives
Camptothecin - pharmacology
Cell Proliferation - drug effects
chemotherapy
Collagen Type IV - metabolism
Colon - cytology
Colon - drug effects
Dose-Response Relationship, Drug
Extracellular Matrix - drug effects
Extracellular Matrix - metabolism
extracellular matrix components
Female
Fibronectins - metabolism
histopathology
Jejunum - cytology
Jejunum - drug effects
Laminin - metabolism
Models, Animal
mucositis
Original
Rats
Rats, Inbred Strains
Time Factors
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Summary:Summary Chemotherapy‐induced mucositis is characterized by damage of mucous membranes throughout the alimentary tract (AT). Extracellular matrix (ECM) components play a vital role in maintaining mucosal barrier integrity by regulating cellular apoptosis, proliferation and differentiation of overlying epithelial cells. The aims of this study were to characterize the changes in epithelial cell kinetics and to investigate the expression of the ECM components in the gastrointestinal tract following irinotecan administration. Female dark agouti rats were treated with single 200 mg/kg dose irinotecan and killed at various time points (1, 6, 24, 48, 72, 96 and 144 h) after treatment. Ki67 immunostaining and TUNEL were used to assess proliferation and apoptosis, respectively, in the jejunum and colon. Masson trichrome staining and picro‐sirius red staining were used to determine the level of collagen, and immunohistochemistry was used to further assess collagen IV, fibronectin and laminin 1 and 2 expression in these tissues. Irinotecan halved cellular proliferation in the jejunum and colon at 48 and 24 h, respectively, while apoptosis peaked at 6 h (P 
ISSN:0959-9673
1365-2613
DOI:10.1111/j.1365-2613.2011.00771.x