Skin healing under treatment with monoterpene (menthol) and triterpene (Lupeol) in experimental model

Abstract

The loss of skin integrity due to physical, chemical or thermal injuries results in the formation of a wound. In consequence, the healing process is triggered, reestablishing the function and integrity of the injured skin. The healing process is classified into three overlapping phases: inflammatory (hemostasis and inflammation), proliferative (granulation tissue formation and reepithelization) and extracellular matrix remodeling phase. Menthol and lupeol presents antinociceptive, antiinflammatory and antimicrobial effects. This research project aims to evaluate the healing potential from menthol and lupeol, in topical cream, in cutaneous wounds in rats and horses, elucidating the mechanism of action. Male Wistar rats (n=7) or horses will be distributed into groups: ointment base (control), collagenase cream (positive control), lupeol or menthol ointment at 2.5, 5 and 10% (w/w). After anesthesia, a circular excision of 2 cm of diameter will be created on the dorsal region of the animals. The wounds will be treated and measured daily for 3, 7 or 21 days (according to the phases described in the literature). After euthanasia, histological (inflammatory cells count, inflammatory score, morphology of collagen fibers), histomorphometrical (regenerative epithelium height measurement) and immunohistochemistry (epidermal and vascular endothelial growth factors, cell proliferation, apoptosis and cytoprotection) analyses will be performed, besides molecular analyses (qPCR and RT-PCR for collagen I and III, epidermal and ²1-transforming growth factor). Analyses of antioxidant activity (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and myeloperoxidase) will be performed in the liver of the rats and analyses of anti-inflammatory activity (tumor necrosis factor-±, pro-inflammatory interleukins IL-1² and IL-6 and anti-inflammatory interleukin IL-10) will be performed in the rats' serum. (AU)