Analysis of biochemical, cellular and molecular mechanisms in rat skin wound healing using creams of hydroalcoholic extract and oleoresin of Copaifera langsdorffii

Author(s)

Lucas Fernando Sérgio Gushiken

• Document type: Master's Dissertation
• Press: Botucatu. 2017-03-29.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2017-02-23
• Advisor: Cláudia Helena Pellizzon; Ariane Leite Rozza

Abstract

The skin is fundamental to maintain the integrity of the body and the disruption of this system promotes the wound healing mechanism, physiological process that can be divided into inflammatory, proliferative and remodeling phases. The skin wounds have great importance in the investment of public resources due to the possibility of some type of physical disability or even death. The Copaifera langsdorffii Desf. (Leguminosae) is a tree that, according to popular knowledge, has anti-inflammatory, antimicrobial and wound healing activities. Therefore, the aim of this study was to investigate the healing potential of the ointments containing hydroalcoholic extracts of the leaves (10% EH) or oleoresin of the bark (10% OR) of Copaifera langsdorffii in cutaneous wounds of rats and the mechanisms involved. Male Wistar rats were randomly divided into four experimental groups (n = 8): lanette ointment (negative control - vehicle), Collagenase 1.2 IU ointment (positive control), 10% EH or 10% OR ointments. The animals were submitted to anesthesia and induction of the dorsal lesion of 2 cm in diameter. The lesions were treated once a day and had their areas measured for 3, 7 and 14 days. After euthanasia, the wounds were assigned to molecular, histological, immunohistochemical analysis and determination of the local anti-inflammatory activity. Our results show the healing potential of treatments 10% EH and 10% OR, with significant retraction of the wounds compared to the Lanette group. The copaiba-based treatments showed anti-inflammatory activity, with reduction of pro-inflammatory cytokines and increase of the anti-inflammatory cytokine IL-10. Molecular and immunohistochemical results showed the activity of 10% EH and 10% OR in the mechanisms of cell proliferation, VEGF-stimulated angiogenesis, reepithelialization mediated by EGF, MMP-2 and MMP-9, MIF-stimulated wound retraction and remodeling of collagen fibers. Thus, the treatments 10% EH and 10% OR presented great potential in skin wound healing, with better results than the reference drug in the proliferation, angiogenesis and retraction of the lesion and presenting similar results as the reference drug in reepithelialization and remodeling, with great potential in the skin wound healing. (AU)

• FAPESP's process: 14/23684-5 - Evaluation of cellular and molecular mechanisms in skin wound healing using Copaifera langsdorffii hydroalcoholic extract and oil resin ointments
• Grantee: Lucas Fernando Sérgio Gushiken
• Support Opportunities: Scholarships in Brazil - Master