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The novel mechanism of valproate to prevent peritoneal adhesion formation

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Abstract

Purpose

A novel pharmacological mechanism of valproate was analyzed using a hamster model of adhesion.

Methods

Valproate or placebo was administered just after cecal injury and adhesion severity scores and histological were analyzed.

Results

The adhesion severity scores in the placebo- and valproate-treated groups were 2.67 ± 0.42 and 1.0 ± 0.37, respectively, with a significant difference between the groups. A significant increase in mast cell numbers was observed in the placebo-treated group vs. the sham-operated group; however, the mast cell number in the adhesive lesion was significantly lower in the valproate-treated group than in the placebo-treated group. The number of cells positive for chymase, an enzyme in mast cells, in the adhesive lesion was significantly higher in the placebo-treated group, but its increase was attenuated significantly by treatment with valproate. The myeloperoxidase gene expression level in the cecum was significantly higher in the placebo-treated group than in the sham-operated group, but there was no significant difference in the myeloperoxidase gene expression level between the sham-operated and valproate-treated groups in. In an in vitro experiment, valproate inhibited purified human and hamster chymases dose-dependently.

Conclusion

The chymase inhibitory effect of valproate may contribute to prevent adhesion formation after abdominal injury.

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Funding

This study was partially supported by Grants 61671098 and 31560312 from the National Nature Science Foundation of China and Grants 17K09741 and 18K06709 from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Chronic Disease Research Center, Medical College, Dalian University, Dalian, 116622, Liaoning, China

    Shuangping Liu, Liping Liu & Qinggao Zhang

  2. Department of Innovative Medicine, Osaka Medical College, Takatsuki, 569-8686, Japan

    Denan Jin & Shinji Takai

Authors
  1. Shuangping Liu
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  2. Liping Liu
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  3. Denan Jin
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  4. Qinggao Zhang
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  5. Shinji Takai
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Contributions

SL: conception, investigation, and formal analysis; LL: conception, investigation, and formal analysis; DJ: investigation, formal analysis, and validation; QZ: project administration, supervision, writing—review, and editing; ST: project administration, supervision, writing—review, and editing. All authors contributed to the research.

Corresponding authors

Correspondence to Qinggao Zhang or Shinji Takai.

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Liu, S., Liu, L., Jin, D. et al. The novel mechanism of valproate to prevent peritoneal adhesion formation. Surg Today 50, 1091–1098 (2020). https://doi.org/10.1007/s00595-020-01979-8

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  • DOI: https://doi.org/10.1007/s00595-020-01979-8

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