Efeitos do resveratrol sobre o processo cicatricial de feridas cutâneas em modelos experimentais com e sem obesidade

Abstract

Obesity is one of the most growing public health problems in the world, with a significant impact on the increase in morbidity and mortality rates. Furthermore, recent research has focused on the mechanisms by which obesity can delay the healing of skin wounds. Much research has been done on the extensive biological property of resveratrol in activating and inhibiting numerous molecular targets. However, it is noted that there are still gaps in the literature regarding the mechanisms of action of resveratrol in the wound healing process, especially in situations of obesity. In view of the above, the present study aimed to review, in the scientific literature, the effects of resveratrol on healing processes and to evaluate the effects of the topical formulation of ointment containing 2% resveratrol on the tissue of excisional skin wounds in experimental animal models with and without obesity. This thesis presents three scientific products about the effects of resveratrol on wound healing. The first article is a narrative review, the objective of which was to perform a complete and in-depth analysis of what the world's scientific literature has already produced on the effects of resveratrol on the wound healing process. Three in vitro studies, 27 in vivo studies, two in silico studies and one clinical study were analyzed, which evaluated the various mechanisms of action of resveratrol, which are potentially involved in wound healing. The studies showed that resveratrol is capable of inhibiting inflammation, increasing the synthesis of collagen fibers, increasing granulation, enhancing angiogenesis, scar formation and improving wound healing. Additionally, resveratrol favors the reconstruction and increase in the thickness of the epidermis, promotes the secretion of growth factors related to wound healing, in addition to implying in reduced wound areas, contributing to epidermal regeneration and organized collagen deposition. The second product is an experimental study conducted with 32 male mice of the SWISS line, which were randomly divided into four groups (n=8 animals/group): i) standard diet + placebo (DP+VEI), ii) standard diet + 2% resveratrol-based ointment associated with Transcutol® CG 1% and Pentravan® (DP+RES), iii) hyperglycemic diet + placebo (DHG+VEI) and, iv: DHG + 2% resveratrol-based ointment associated with Transcutol® CG 1% and Pentravan® (DHG+RES). The excisional wound was made in the dorsal region. The treatments were applied for 14 days. To verify the kinetics of wound closure, the wound area was measured on days 3, 5, 7, 10 and 14 of treatment. On days 7 and 14, the animals were euthanized and wound tissue samples were processed for hematoxylin and eosin and Masson's trichrome staining. The expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF) and transforming growth factor beta (TGFb) were evaluated. This study concluded that resveratrol accelerated the kinetics of wound healing compared to the other groups. Histological analysis demonstrated that wounds treated with 2% resveratrol developed improved anatomical characteristics of the skin, as well as increased angiogenesis. Molecular analysis of epithelial tissue showed that the groups treated with 2% resveratrol-based ointment presented increased TGFb, VEGF and FGF. Topical treatment with 2% resveratrol-based ointment increases the expression of factors important for healing. In view of these results, the third product was generated, a patent application for the use of the topical ointment formulation containing 2% resveratrol developed in the present study. The results provide strong evidence of the healing activity of resveratrol. However, it is important to highlight the importance of conducting further clinical studies to investigate the effects of resveratrol on the wound healing process.