{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:07:02Z","timestamp":1776060422946,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms23031021","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T08:09:20Z","timestamp":1642493360000},"page":"1021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chemotherapeutics Combined with Luminal Irritants: Effects on Small-Intestinal Mannitol Permeability and Villus Length in Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2950-6737","authenticated-orcid":false,"given":"Maria-Jos\u00e9","family":"Cano-Cebri\u00e1n","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Burjasot, Spain"},{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, 752 36 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5586-2906","authenticated-orcid":false,"given":"David","family":"Dahlgren","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, 752 36 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-4198","authenticated-orcid":false,"given":"Fredrik","family":"Kullenberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, 752 36 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1384-2103","authenticated-orcid":false,"given":"Karsten","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, 752 36 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Olander","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, 752 36 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1406-9389","authenticated-orcid":false,"given":"Markus","family":"Sj\u00f6blom","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology, Division of Physiology, Uppsala University, 751 23 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1578-5184","authenticated-orcid":false,"given":"Hans","family":"Lennern\u00e4s","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, 752 36 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/cncr.33587","article-title":"The ever-increasing importance of cancer as a leading cause of premature death worldwide","volume":"127","author":"Bray","year":"2021","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1124\/dmd.114.058404","article-title":"Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans","volume":"42","author":"Darwich","year":"2014","journal-title":"Drug Metab. 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