Relationship between GLP-2 dynamics and tissue injury in rat intestine after anti-cancer drugs administration
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- Shiga Saki
- Health Sciences University of Hokkaido, Japan
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- Machida Takuji
- Health Sciences University of Hokkaido, Japan
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- Machida Maiko
- Hokkaido Pharmaceutical University School of Pharmacy, Japan
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- Hirafuji Masahiko
- Health Sciences University of Hokkaido, Japan
抄録
<p>Background: Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone secreted from intestinal L-cells. GLP-2 is known to improve and maintain intestinal homeostasis, and shows therapeutic efficacy in small and large bowel inflammation. To clarify the relationship between intestinal GLP-2 dynamics and chemotherapy-induced intestinal injury, we investigated the GLP-2 dynamics in rat small intestine after administration of either methotrexate or 5-fluorouracil. </p><p>Methods: Rat were i.p. injected with either methotrexate (50 mg/kg) or 5-fluorouracil (100 mg/kg). At an appropriate time after the injection, the intestinal tissues were dissected out and frozen rapidly in liquid nitrogen and stored until further analysis. Myeloperoxidase and GLP-2 expression and localization were analyzed by immunohistochmical analysis. mRNA expression was analyzed by RT-qPCR. </p><p>Results: A single administration of 5-fluorouracil caused intestinal damage in a time-dependent manner up to 72 hrs, whereas methotrexate had almost no effect. At 24 hrs after administration, methotrexate significantly increased mRNA expressions of proglucagon, a precursor of GLP-2, GLP-2 receptor and insulin-like growth factor-1, an essential factor of the intestinal tropic effects of GLP-2. Numbers of anti-GLP-2 antibody positive cells in the intestine were also increased by methotrexate administration. On the other hand, 5-fluorouracil significantly reduced these mRNA expressions as well as the numbers of anti-GLP-2 antibody positive cells. Methotrexate and 5-fluorouracil slightly and significantly increased mRNA expression of dipeptidyl peptidase-4 which inactivates GLP-2, respectively. </p><p>Conclusion: Methotrexate accelerated intestinal GLP-2 dynamics without obvious intestinal injury, whereas 5-fluorouracil inhibited the dynamics with serious injury. These results suggest that the effect of anti-cancer drugs on intestinal GLP-2 dynamics is closely correlates with chemotherapy-induced intestinal injury. Methotrexate-induced upregulation of intestinal GLP-2 dynamics may contribute to counteract the intestinal damage by methotrexate.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 WCP2018 (0), PO2-6-26-, 2018
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390004222616886656
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- NII論文ID
- 130007901232
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- ISSN
- 24354953
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可