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

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...

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Autores principales: Anders B. Nexoe, Andreas A. Pedersen, Sebastian von Huth, Grith L. Sorensen, Uffe Holmskov, Ping-Ping Jiang, Sönke Detlefsen, Steffen Husby, Mathias Rathe
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:2008085a1e9147e48fd1bb671d0f232c2021-12-02T16:17:17ZNo effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis10.1038/s41598-021-94076-w2045-2322https://doaj.org/article/2008085a1e9147e48fd1bb671d0f232c2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94076-whttps://doaj.org/toc/2045-2322Abstract 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.Anders B. NexoeAndreas A. PedersenSebastian von HuthGrith L. SorensenUffe HolmskovPing-Ping JiangSönke DetlefsenSteffen HusbyMathias RatheNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Anders B. Nexoe
Andreas A. Pedersen
Sebastian von Huth
Grith L. Sorensen
Uffe Holmskov
Ping-Ping Jiang
Sönke Detlefsen
Steffen Husby
Mathias Rathe
No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
description 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.
format article
author Anders B. Nexoe
Andreas A. Pedersen
Sebastian von Huth
Grith L. Sorensen
Uffe Holmskov
Ping-Ping Jiang
Sönke Detlefsen
Steffen Husby
Mathias Rathe
author_facet Anders B. Nexoe
Andreas A. Pedersen
Sebastian von Huth
Grith L. Sorensen
Uffe Holmskov
Ping-Ping Jiang
Sönke Detlefsen
Steffen Husby
Mathias Rathe
author_sort Anders B. Nexoe
title No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
title_short No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
title_full No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
title_fullStr No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
title_full_unstemmed No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
title_sort no effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/2008085a1e9147e48fd1bb671d0f232c
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