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Supraphysiological testosterone supplementation improves granulation tissue maturation through angiogenesis in the early phase of a cutaneous wound healing model in rats

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Abstract

Objective

The aim of this study was to evaluate the effects of both testosterone depletion and supraphysiological testosterone supplementation in the early phase of an animal cutaneous wound healing model in comparison with the physiological hormonal condition.

Material and Methods

Forty rats were distributed into the following four groups: Control, Orchiectomy (OCX), Durateston (Dura) and OCX+Dura. On day 1, the testicles were removed (OCX group) and the rats (Dura group) received a supraphysiological dose (250 mg/kg) of exogenous testosterone weekly. After 15 days a full-thickness excisional skin wound was created in all animals, which was healed by the second intention for 7 days. On day 22, the rats were euthanatized and the wounds were harvested for histopathological evaluation, immunohistochemistry analyses and multiplex immunoassay. One-way ANOVA and post-hoc Tukey tests were performed.

Results

It was found that the supraphysiological testosterone level increased extracellular matrix deposition, promoted higher blood vessel formation and reduced wound contraction (p < 0.05). Additionally, it also stimulated PCNA-positive fibroblasts and KGF-positive cells (p < 0.05), while orchiectomy reduced the expression of IL-6 and TNF-α and increased VEGF and PDGF (p < 0.05) .

Conclusion

In conclusion, the results provide evidence that supraphysiological testosterone supplementation plays a positive role in the early phase of cutaneous wound healing, thus improving granulation tissue maturation through the enhancement of angiogenesis.

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Funding

This work was supported by São Paulo State Research Support Foundation (FAPESP) – Number 2015/20281–0.

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Authors and Affiliations

  1. Department of Physiology and Pathology, Araraquara School of Dentistry, University of São Paulo State, UNESP, Humaitá St., 1680 – Center, Araraquara, SP, 14801-903, Brazil

    Vinícius de Paiva Gonçalves & Luís Carlos Spolidorio

  2. Department of Stomatology, Federal University of Paraná, UFPR, Pref. Lothário Meissner Av., 632 – Center, Curitiba, PR, 80210-170, Brazil

    João Paulo Steffens

  3. Department of Diagnosis and Surgery, Araraquara School of Dentistry, University of São Paulo State, UNESP, Humaitá St., 1680 – Center, Araraquara, SP, 14801-903, Brazil

    Carlos Rossa Junior

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  1. Vinícius de Paiva Gonçalves
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  4. Luís Carlos Spolidorio
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Correspondence to Vinícius de Paiva Gonçalves.

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The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical Approval

All animal procedures were conducted in compliance with Brazilian National Council for the Control of Animal Experimentation with ethical standards that fully comply with Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. The experimental protocol was approved by the Local Ethics Committee on the Use of Animals (Process CEUA/FOAr #47/2014).

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de Paiva Gonçalves, V., Steffens, J.P., Junior, C.R. et al. Supraphysiological testosterone supplementation improves granulation tissue maturation through angiogenesis in the early phase of a cutaneous wound healing model in rats. Inflamm. Res. 71, 473–483 (2022). https://doi.org/10.1007/s00011-022-01553-7

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  • DOI: https://doi.org/10.1007/s00011-022-01553-7

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