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Chemotherapeutics Combined with Luminal Irritants: Effects on Small-Intestinal Mannitol Permeability and Villus Length in Rats

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Chemotherapeutics Combined with Luminal Irritants: Effects on Small-Intestinal Mannitol Permeability and Villus Length in Rats

dc.contributor.author	Cano Cebrián, María José
dc.contributor.author	Dahlgren, David
dc.contributor.author	Kullenberg, Fredrik
dc.contributor.author	Peters, Karsten
dc.contributor.author	Olander, Tobias
dc.date.accessioned	2023-11-16T13:44:12Z
dc.date.available	2023-11-16T13:44:12Z
dc.date.issued	2022
dc.identifier.uri	https://hdl.handle.net/10550/91217
dc.description.abstract	Chemotherapy causes intestinal mucositis, which includes villous atrophy and altered mucosal barrier function. However, there is an uncertainty regarding how the reduced small-intestinal surface area affects the mucosal permeability of the small marker probe mannitol (MW 188), and how the mucosa responds to luminal irritants after chemotherapy. The aims in this study were to determine (i) the relationship between chemotherapy-induced villus atrophy and the intestinal permeability of mannitol and (ii) how the mucosa regulate this permeability in response to luminal ethanol and sodium dodecyl sulfate (SDS). This was investigated by treating rats with a single intraperitoneal dose of doxorubicin, irinotecan, or 5-fluorouracil. After 72 h, jejunum was single-pass perfused and mannitol permeability determined at baseline and after 15 min luminal exposure to 15% ethanol or 5 mg/mL SDS. Tissue samples for morphological analyses were sampled from the perfused segment. All three chemotherapeutics caused a similar 30% reduction in villus length. Mannitol permeability increased with irinotecan (1.3-fold) and 5-fluorouracil (2.5-fold) and was reduced with doxorubicin (0.5-fold), suggesting that it is not epithelial surface area alone that regulates intestinal permeability to mannitol. There was no additional increase in mannitol permeability induced by luminal ethanol or SDS in the chemotherapy-treated rats compared to controls, which may be related to the relatively high basal permeability of mannitol compared to other common low-permeability probes. We therefore suggest that future studies should focus on elucidating the complex interplay between chemotherapy in combination with luminal irritants on the intestinal permeability of other probes.
dc.language.iso	eng
dc.relation.ispartof	International Journal Of Molecular Sciences, 2022, vol. 23, num. 3, p. 1021
dc.source	Cano Cebrián, María José Dahlgren, David Kullenberg, Fredrik Peters, Karsten Olander, Tobias 2022 Chemotherapeutics Combined with Luminal Irritants: Effects on Small-Intestinal Mannitol Permeability and Villus Length in Rats International Journal Of Molecular Sciences 23 3 1021. https://doi.org/10.3390/ijms23031021
dc.subject	quimioteràpia
dc.subject	farmacologia
dc.title	Chemotherapeutics Combined with Luminal Irritants: Effects on Small-Intestinal Mannitol Permeability and Villus Length in Rats
dc.type	journal article
dc.date.updated	2023-11-16T13:44:12Z
dc.identifier.doi	10.3390/ijms23031021
dc.identifier.idgrec	150233
dc.rights.accessRights	open access