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Kamiya A, Machida T, Hirano M, et al. Administration of cyclophosphamide to rats induces pica and potentiates 5-hydroxytryptamine synthesis in the intestine without causing severe intestinal injury. J Pharmacol Sci. 2021;147(3):251-259doi: 10.1016/j.jphs.2021.07.007.
Kamiya, A., Machida, T., Hirano, M., Machida, M., Shiga, S., Hamaue, N., Hirafuji, M., & Iizuka, K. (2021). Administration of cyclophosphamide to rats induces pica and potentiates 5-hydroxytryptamine synthesis in the intestine without causing severe intestinal injury. Journal of pharmacological sciences, 147(3), 251-259. https://doi.org/10.1016/j.jphs.2021.07.007
Kamiya, Akihisa, et al. "Administration of cyclophosphamide to rats induces pica and potentiates 5-hydroxytryptamine synthesis in the intestine without causing severe intestinal injury." Journal of pharmacological sciences vol. 147,3 (2021): 251-259. doi: https://doi.org/10.1016/j.jphs.2021.07.007
Kamiya A, Machida T, Hirano M, Machida M, Shiga S, Hamaue N, Hirafuji M, Iizuka K. Administration of cyclophosphamide to rats induces pica and potentiates 5-hydroxytryptamine synthesis in the intestine without causing severe intestinal injury. J Pharmacol Sci. 2021 Nov;147(3):251-259. doi: 10.1016/j.jphs.2021.07.007. Epub 2021 Aug 02. PMID: 34507634.
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J Pharmacol Sci. 2021 Nov;147(3):251-259. doi: 10.1016/j.jphs.2021.07.007. Epub 2021 Aug 02.

Administration of cyclophosphamide to rats induces pica and potentiates 5-hydroxytryptamine synthesis in the intestine without causing severe intestinal injury.

Journal of pharmacological sciences

Akihisa Kamiya, Takuji Machida, Megumi Hirano, Maiko Machida, Saki Shiga, Naoya Hamaue, Masahiko Hirafuji, Kenji Iizuka

Affiliations

  1. Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
  2. Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. Electronic address: [email protected].
  3. Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, Japan.
  4. Department of Hygienic Chemistry, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.

PMID: 34507634 DOI: 10.1016/j.jphs.2021.07.007

Abstract

The effects of cyclophosphamide on 5-hydroxytryptamine (5-HT) synthesis in the intestinal tissue of rats were investigated. Rats received 120 mg/kg cyclophosphamide intraperitoneally as a single administration, and kaolin and food intake was measured by an automatic monitoring apparatus. Ileal tissues were collected at either 24 or 72 h after administration. Cyclophosphamide caused a significant increase in kaolin intake at the acute and the delayed phases and was associated with a decrease in food intake, and body weight. Cyclophosphamide had no significant effect on intestinal mucosal morphology, or inducible nitric oxide synthase and cyclooxygenase-2 expression in the intestine. Cyclophosphamide significantly increased tryptophan hydroxylase 1 (TPH1) mRNA expression, number of anti-TPH antibody-positive cells, and 5-HT content in the intestine. Cyclophosphamide also significantly increased the expression of Tac1 mRNA, encoding preprotachykinin-1, which is a preprotein of substance P, and the number of anti-substance P antibody-positive cells in the intestine. Cyclophosphamide significantly increased Lgr5, Bmi1, and Atoh1 mRNA levels, which are markers for the proliferation and differentiation of stem cells. This study demonstrated that cyclophosphamide induced pica in rats, and potentiated 5-HT synthesis associated with hyperplasia of substance P-containing enterochromaffin cells without causing severe intestinal injury.

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Keywords: 5-Hydroxytriptamine; Cyclophosphamide; Intestine; Pica; Substance P

Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

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