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Cisplatin increases the number of enterochromaffin cells containing substance P in rat intestine

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Abstract

We previously reported that cisplatin potentiated ileal 5-hydroxytryptamine (5-HT) metabolism and caused pathological changes with an inflammatory response in the delayed phase (72 h) after administration to rats. In the present study, we further investigated the time-dependent effect of cisplatin on ileal 5-HT metabolism and the effects of combining cisplatin and anti-inflammatory drugs on ileal tryptophan hydroxylase expression and pica (the consumption of non-nutritive materials such as kaolin). Cyclooxygenase-2 (COX-2) expression was significantly increased at 24 h after cisplatin (5 mg/kg, intraperitoneal) administration. Cisplatin significantly increased ileal 5-HT content at 48 h after administration and the number of L-tryptophan hydroxylase-expressing cells (i.e., enterochromaffin cells) in the ileal mucosa within 24 h after administration. It also caused a significant increase in the number of substance P-expressing cells. Immunohistochemical double staining revealed that most of the enterochromaffin cells contained substance P. Neither daily treatment with dexamethasone (1 mg/kg, subcutaneous) nor meloxicam (3 mg/kg, subcutaneous), a selective COX-2 inhibitor, affected the cisplatin-induced increase in the number of enterochromaffin cells. Meloxicam had no effect on cisplatin-induced pica, although dexamethasone almost completely inhibited it. This study demonstrated that cisplatin administration induced COX-2 expression and increased the number of enterochromaffin cells in the acute phase (i.e., within 24 h). However, COX-2 expression in the ileum seems to have little direct effect on the mechanism of the induction of enterochromaffin cells and pica.

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Authors and Affiliations

  1. Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan

    Yusuke Obara, Takuji Machida, Yuho Takano, Saki Shiga, Asami Suzuki, Kenji Iizuka & Masahiko Hirafuji

  2. Department of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan

    Naoya Hamaue

Authors
  1. Yusuke Obara
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  2. Takuji Machida
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  3. Yuho Takano
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  4. Saki Shiga
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  5. Asami Suzuki
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  6. Naoya Hamaue
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  7. Kenji Iizuka
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  8. Masahiko Hirafuji
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Correspondence to Takuji Machida.

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Obara, Y., Machida, T., Takano, Y. et al. Cisplatin increases the number of enterochromaffin cells containing substance P in rat intestine. Naunyn-Schmiedeberg's Arch Pharmacol 391, 847–858 (2018). https://doi.org/10.1007/s00210-018-1493-5

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  • DOI: https://doi.org/10.1007/s00210-018-1493-5

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