No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis

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Abstract

Mucositis is a serious adverse effect of chemotherapeutic treatment. During intestinal mucositis, the mucosal barrier is compromised, increasing the risk of severe infections. Mucositis necessitates dose reduction or pauses in treatment, which affect the outcome of the treatment. Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger protein with effects on innate immunity and epithelial regeneration. We have previously shown that jejunal DMBT1 expression is increased in piglets during chemotherapeutic treatment. We hypothesized that DMBT1 ameliorates doxorubicin-induced mucositis. Individually-caged Dmbt1+/+ (WT) and Dmbt1−/− (KO) female mouse littermates received intraperitoneal injections of either doxorubicin or saline. They were euthanized after three (D3) or seven days (D7). Weight loss was monitored every day, and serum citrulline levels were measured at termination. Intestinal tissue was analyzed for the expression of DMBT1 and proinflammatory cytokines (IL-1β, IL-6, and TNF). Specimens from the small intestines and colon were scored for inflammation and epithelial and mucosal architecture changes. We detected no effect of DMBT1 on weight loss, serum citrulline levels, expression of proinflammatory cytokines, or histologic damage. We detected a significant increase in crypt depth in WT mice compared to that in KO mice on D3. In conclusion, DMBT1 does not affect doxorubicin-induced mucositis in mice.

OriginalsprogEngelsk
Artikelnummer14687
TidsskriftScientific Reports
Vol/bind11
Udgave nummer1
Antal sider11
ISSN2045-2322
DOI
StatusUdgivet - 19. jul. 2021

Bibliografisk note

Funding Information:
We gratefully thank M.Sc. Kimmie B. Colmorten, University of Southern Denmark, Department of Cancer and Inflammation Research, for proofreading of the manuscript and valuable input and criticism, and Maria Fuglsang Bruun, Department of Pathology, Odense University Hospital, for aiding in the scoring of histological damage. This study was supported by grants from the Odense University Hospital Free Research Fund, The Danish Cancer Society, the Danish Child Cancer Foundation, and Overlægerådets Forskningsfond.

Publisher Copyright:
© 2021, The Author(s).

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