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Effects of topical topiramate in wound healing in mice

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Abstract

Recent studies have indicated that systemic topiramate can induce an improvement on the aesthetic appearance of skin scars. Here, we evaluated topical topiramate as an agent to improve wound healing in C57/BL6 mice. Mice were inflicted with a 6.0 mm punch to create two wounds in the skin of the dorsal region. Thereafter, mice were randomly assigned to either vehicle or topical topiramate (20 µl of 2% cream) once a day for 14 days, beginning on the same day as wound generation. We analyzed the wound samples over real-time PCR, Western blotting, and microscopy. There was no effect of the topiramate treatment on the time for complete reepithelization of the wound. However, on microscopic analysis, topiramate treatment resulted in increased granulation tissue, thicker epidermal repair, and improved deposition of type I collagen fibers. During wound healing, there were increased expressions of anti-inflammatory markers, such as IL-10, TGF-β1, and reduced expression of the active form of JNK. In addition, topiramate treatment increased the expression of active forms of two intermediaries in the insulin-signaling pathway, IRS-1 and Akt. Finally, at the end of the wound-healing process, topiramate treatment resulted in increased expression of SOX-2, a transcription factor that is essential to maintain cell self-renewal of undifferentiated embryonic stem cells. We conclude that topical topiramate can improve the overall quality of wound healing in the healthy skin of mice. This improvement is accompanied by reduced expression of markers involved in inflammation and increased expression of proteins of the insulin-signaling pathway.

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Acknowledgements

We thank Dr. E. Roman, G. Ferraz, and M. Cruz for technical assistance. Sao Paulo Research Foundation and Coimbra Group of Brazilian Universities Education provided the grants for this study. The authors belong to the Obesity and Comorbidities Research Center, Brazil.

Funding

This work was supported by grant from São Paulo Research Foundation—CEPID-OCRC—Obesity Comorbidities Center.

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Authors and Affiliations

  1. Nursing School, University of Campinas, Campinas, SP, 13084-970, Brazil

    Carlos Poblete Jara, Vanessa Cristina Dias Bóbbo, Maria H. M. Lima & Eliana P. Araújo

  2. Laboratory of Cell Signaling, University of Campinas, Campinas, SP, 13084-970, Brazil

    Carlos Poblete Jara, Vanessa Cristina Dias Bóbbo, Rodrigo Scarpari Carraro, Thiago Matos Ferreira de Araujo, Maria H. M. Lima, Licio A. Velloso & Eliana P. Araújo

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  1. Carlos Poblete Jara
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Correspondence to Eliana P. Araújo.

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The Ethics Committee of the University of Campinas approved all experiments.

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Jara, C.P., Bóbbo, V.C.D., Carraro, R.S. et al. Effects of topical topiramate in wound healing in mice. Arch Dermatol Res 310, 363–373 (2018). https://doi.org/10.1007/s00403-018-1822-z

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