Avaliação da atividade cicatrizante de derivados de tiossemicarbazonas no tratamento de feridas em ratos

Abstract

Healing is a process that aims to restore tissue integrity, but in the presence of comorbidities such as diabetes, obesity, atherosclerosis, infection and chronic wounds, for example, this physiological process can be delayed. Topical substances have been tested in the interest of optimizing the time, the quality of the scar and the costs inherent to the process. This study evaluated the healing activity of two thiosemicarbazone derivatives in Wistar rats. These synthetic substances have scientific value and interest due to the versatility of their chemical and biological properties and because they are bioisteroids of aminoguanidine, a substance already known for having several properties (including healing). The two thiosemicarbazone derivatives that showed better anti-glycant activity and showed no toxicity were selected for the in vivo assay. The in vivo experiments were conducted at the Laboratory of Cardiovascular Pharmacology of the Institute of Pharmaceutical Sciences at UFAL, under the approval of CEUA / UFAL nº 06/2019. The 36 animals were randomly divided into 4 groups with 9 animals each: CP (positive control), CN (negative control), LQM 9.1 (derivative 1) and LQM 11.1 (derivative 2). They were submitted to anesthesia, to circular excisions with punch in the dorsal region and topical creams were applied to the wounds containing the substances. Dressings and wound assessment were performed daily for 21 days. Euthanasias occurred at each stage of healing (on the 7th, 14th and on the 21st day, with the sacrifice of 12 animals each day). For macroscopic analysis, the following variables were considered: repilation, hyperemia, clot, presence of bleeding, wound retraction, exudate, hyperplasia at the edges of the wound, inflammation, wound size. For histological analysis by microscopy of the treated wounds, the flaps were stained with hematoxylin-eosin and the evaluated criteria were: presence of clot (crust), hyperplasia at the edges of the wound, presence of infection, presence of inflammation, inflammatory components, granulation tissue, cell proliferation (macrophages and fibroblasts) and collagen deposition at the center and at the edges of the wound. After the analysis, it was found that the tested substances did not show toxicity according to the concentration at which they were tested (10µM). Characteristics were observed that demonstrated an acceleration of healing in phases 1 and 2 (granulation, wound retraction and little exudate), with abbreviation of the proliferative phase (phase 2) and characteristics of the remodeling phase (phase 3). It was found that microscopically, in phase 2, the wounds no longer had hyperplasia at the edge of the wound and macroscopically they had a scarred appearance, demonstrating that thiosemicarbazone derivatives can be low-cost and promising prototypes for rapid healing.