Skip to main content
Top
Published in: Archives of Dermatological Research 4/2018

01-05-2018 | Original Paper

Effects of topical topiramate in wound healing in mice

Authors: 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

Published in: Archives of Dermatological Research | Issue 4/2018

Login to get access

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.
Literature
3.
go back to reference Benoliel AM, Kahn-Perles B, Imbert J, Verrando P (1997) Insulin stimulates haptotactic migration of human epidermal keratinocytes through activation of NF-kappa B transcription factor. J Cell Sci 110(Pt 17):2089–2097PubMed Benoliel AM, Kahn-Perles B, Imbert J, Verrando P (1997) Insulin stimulates haptotactic migration of human epidermal keratinocytes through activation of NF-kappa B transcription factor. J Cell Sci 110(Pt 17):2089–2097PubMed
4.
go back to reference Bharti R, Agarwal L (2005) Topiramate and scars. Dermatol Online J 11(3):42PubMed Bharti R, Agarwal L (2005) Topiramate and scars. Dermatol Online J 11(3):42PubMed
5.
go back to reference Caricilli AM, Penteado E, de Abreu LL, Quaresma PG, Santos AC, Guadagnini D, Razolli D, Mittestainer FC, Carvalheira JB, Velloso LA, Saad MJ, Prada PO (2012) Topiramate treatment improves hypothalamic insulin and leptin signaling and action and reduces obesity in mice. Endocrinology 153(9):4401–4411. https://doi.org/10.1210/en.2012-1272 CrossRefPubMed Caricilli AM, Penteado E, de Abreu LL, Quaresma PG, Santos AC, Guadagnini D, Razolli D, Mittestainer FC, Carvalheira JB, Velloso LA, Saad MJ, Prada PO (2012) Topiramate treatment improves hypothalamic insulin and leptin signaling and action and reduces obesity in mice. Endocrinology 153(9):4401–4411. https://​doi.​org/​10.​1210/​en.​2012-1272 CrossRefPubMed
10.
go back to reference Faught E (2007) Topiramate in the treatment of partial and generalized epilepsy. Neuropsychiatr Dis Treat 3(6):811–821PubMedCentralPubMed Faught E (2007) Topiramate in the treatment of partial and generalized epilepsy. Neuropsychiatr Dis Treat 3(6):811–821PubMedCentralPubMed
14.
15.
go back to reference Hish GA Jr, Diaz JA, Hawley AE, Myers DD Jr, Lester PA (2014) Effects of analgesic use on inflammation and hematology in a murine model of venous thrombosis. J Am Assoc Lab Anim Sci 53(5):485–493PubMedCentralPubMed Hish GA Jr, Diaz JA, Hawley AE, Myers DD Jr, Lester PA (2014) Effects of analgesic use on inflammation and hematology in a murine model of venous thrombosis. J Am Assoc Lab Anim Sci 53(5):485–493PubMedCentralPubMed
16.
go back to reference Jaber SM, Hankenson FC, Heng K, McKinstry-Wu A, Kelz MB, Marx JO (2014) Dose regimens, variability, and complications associated with using repeat-bolus dosing to extend a surgical plane of anesthesia in laboratory mice. J Am Assoc Lab Anim Sci 53(6):684–691PubMedCentralPubMed Jaber SM, Hankenson FC, Heng K, McKinstry-Wu A, Kelz MB, Marx JO (2014) Dose regimens, variability, and complications associated with using repeat-bolus dosing to extend a surgical plane of anesthesia in laboratory mice. J Am Assoc Lab Anim Sci 53(6):684–691PubMedCentralPubMed
26.
31.
go back to reference Panayiotopoulos CP (2005) In: The epilepsies: seizures, syndromes and management, chap 4. Bladon Medical Publishing, Oxfordshire. ISBN-10: 1-904218-34-2 Panayiotopoulos CP (2005) In: The epilepsies: seizures, syndromes and management, chap 4. Bladon Medical Publishing, Oxfordshire. ISBN-10: 1-904218-34-2
36.
go back to reference Ryback R (2002) Topiramate in the treatment of psoriasis: a pilot study. Br J Dermatol 147(1):130–133CrossRefPubMed Ryback R (2002) Topiramate in the treatment of psoriasis: a pilot study. Br J Dermatol 147(1):130–133CrossRefPubMed
38.
go back to reference Shapira NA, Lessig M, Murphy TK, Annis AM, Lazoritz M (2003) Evaluation of open-label topiramate for scar therapy. Dermatol Online J 9(5):3PubMed Shapira NA, Lessig M, Murphy TK, Annis AM, Lazoritz M (2003) Evaluation of open-label topiramate for scar therapy. Dermatol Online J 9(5):3PubMed
43.
go back to reference Spanheimer RG, Umpierrez GE, Stumpf V (1988) Decreased collagen production in diabetic rats. Diabetes 37(4):371–376CrossRefPubMed Spanheimer RG, Umpierrez GE, Stumpf V (1988) Decreased collagen production in diabetic rats. Diabetes 37(4):371–376CrossRefPubMed
45.
go back to reference Walraven M, Akershoek JJ, Beelen RH, Ulrich MM (2017) In vitro cultured fetal fibroblasts have myofibroblast-associated characteristics and produce a fibrotic-like environment upon stimulation with TGF-beta1: Is there a thin line between fetal scarless healing and fibrosis? Arch Dermatol Res 309(2):111–121. https://doi.org/10.1007/s00403-016-1710-3 CrossRefPubMed Walraven M, Akershoek JJ, Beelen RH, Ulrich MM (2017) In vitro cultured fetal fibroblasts have myofibroblast-associated characteristics and produce a fibrotic-like environment upon stimulation with TGF-beta1: Is there a thin line between fetal scarless healing and fibrosis? Arch Dermatol Res 309(2):111–121. https://​doi.​org/​10.​1007/​s00403-016-1710-3 CrossRefPubMed
46.
go back to reference Wang XJ, Han G, Owens P, Siddiqui Y, Li AG (2006) Role of TGF beta-mediated inflammation in cutaneous wound healing. J Investig Dermatol Symp Proc 11(1):112–117CrossRefPubMed Wang XJ, Han G, Owens P, Siddiqui Y, Li AG (2006) Role of TGF beta-mediated inflammation in cutaneous wound healing. J Investig Dermatol Symp Proc 11(1):112–117CrossRefPubMed
48.
Metadata
Title
Effects of topical topiramate in wound healing in mice
Authors
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
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 4/2018
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-018-1822-z

Other articles of this Issue 4/2018

Archives of Dermatological Research 4/2018 Go to the issue