Orally administered sodium 4‑phenylbutyrate suppresses the development of dextran sulfate sodium‑induced colitis in mice

Ono,Kazuhiko; Nimura,Satoshi; Hideshima,Yuko; Nabeshima,Kazuki; Nakashima,Manabu

doi:10.3892/etm.2017.5251

Orally administered sodium 4‑phenylbutyrate suppresses the development of dextran sulfate sodium‑induced colitis in mice

Authors:
- Kazuhiko Ono
- Satoshi Nimura
- Yuko Hideshima
- Kazuki Nabeshima
- Manabu Nakashima
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Affiliations: Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Science, Fukuoka University, Fukuoka 814‑0180, Japan, Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka 814‑0180, Japan
Published online on: October 3, 2017 https://doi.org/10.3892/etm.2017.5251
Pages: 5485-5490

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Abstract

Sodium 4‑phenylbutyrate (PBA) exerts therapeutic effects in a wide range of pathologies. A previous study by the present authors revealed that intraperitoneal administration of PBA suppresses the onset of dextran sulfate sodium (DSS)‑induced colitis in mice. In the present study, the effects of orally administered PBA are investigated, as this route of administration is more clinically relevant. The therapeutic efficacy of PBA (10 mg/12 h) in mice with experimental colitis was assessed based on the disease activity index, production of inflammatory cytokines, colon length and histopathological investigations. The results of the present study demonstrated a significantly higher survival rate in the PBA‑treated group compared with the PBA‑untreated (DSS control) group (P=0.0156). PBA treatment improved pathological indices of experimental colitis (P<0.05). Furthermore, the oral administration of PBA significantly inhibited the DSS‑induced shortening of the colon (P<0.05) and overproduction of interleukin (IL)‑1β and IL‑6 (both P<0.05) as measured in colonic lavage fluids. A marked attenuation of the DSS‑induced overproduction of tumor necrosis factor was also observed. For histopathological analysis, a marked decrease in mature goblet cells and increase in enlarged nuclei of the absorptive cells was observed in colon lesions of DSS control mice as compared with normal untreated mice. However, in the PBA‑treated mice, no such lesions were observed and the mucosa resembled that of DSS‑untreated mice. The results of the present study, combined with those results of a previous study, suggest that oral and intraperitoneal administration of PBA have similar preventative effects on DSS‑induced colitis, achieved by suppressing its pathogenesis.

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