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Activity of natural latex biomembrane of Hevea brasiliensis rubber tree and oncostatin M on wound healing in diabetic rats

Grant number: 09/09355-0
Support Opportunities:Regular Research Grants
Duration: August 01, 2009 - July 31, 2011
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marco Andrey Cipriani Frade
Grantee:Marco Andrey Cipriani Frade
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


There are several diseases that affect negatively the process of tissue repair (such as diabetes mellitus). Recent works suggest the importance of ONCOSTATIN M (OSM) protein by stimulating the mitogenic response in fibroblasts, endothelial cells and recruitment of polymorphonuclear (PMN). Goren et al., 2006 showed a relationship between OSM and the infiltration of PMN in recent ulcers. Moreover, they demonstrate a leptin-improved healing of diabetic chronic wounds was associated with a dramatic loss of PMN cell numbers and OSM expression at the wound site. Thus, this study provides evidence that dysregulated OSM expression is functionally connected to the PMN wound infiltrate and associated with impaired healing conditions in chronically inflamed wounds. There is large interest in accelerate healing process especially in diabetic patients and/or immunodepressed in order to avoid complications with very common infections. The Natural Latex Biomembrana (NLB) of the rubber tree Hevea brasiliensis has been studied since 1994. Mendonça, 2004 and Maurício, 2006 performed DEAE-cellulose chromatography of latex and got 3 fractions. The fraction 1 was incorporated in gel with carboxymethyl cellulose 4% in 3 different concentrations: 0.01%, 0.1% and 1% and applied them in skin ulcers on the rabbits' ears. The 0.01% concentration was more efficient by stimulating the closing of injury in less time. In an attempt to seek information on the mechanism of action of NLB in healing, Andrade, 2007 made the implantation of subcutaneous NLB in the back of C57BL/6 mice, for analyzing the new formed tissue followed at the post-surgical moments representative of the inflammatory and tissue formation phases, comparing it with the membrane of denatured latex (surgical GLOVE), synthetic implant (ePTFE) and post-surgical trauma in mice's subcutaneous (SHAM). Using different methodologies such as images analysis by the ImageJ software of histological sections stained with HE, to study inflammatory infiltrate, angiogenesis and fibroplasia; Gomori trichrome to study about the colagenesis; immunohistochemistry for iNOS, IL-1², TGF-²1, VEGF; assays of IL-1² and TGF-²1 by ELISA and myeloperoxidase (determining the neutrophilic function). It was noted the NLB acts significantly in the inflammatory phase of healing, important in the neutrophilic recruitment to the site of injury, confirmed by high level of myeloperoxidase and IL-1². This fact seemed to influence directly at the subsequent phases of the healing process, confirmed by its ability to stimulating angiogenesis, probably not influenced by VEGF, and the stimulus to fibroplasia, independent of TGF-²1 and without modification in collagen production. Frade et al., 2004 used the NLB on wounds of diabetic patients with co-morbidities and complications. They concluded that the NLB acted in different stages of healing, removing necrotic tissue (debridement), stimulating the proliferation and granulation tissue and also the reepithelialization, different from the findings of Frade, 2003 and Frade et al., 2005 in non-diabetic patients, where was not confirmed clinically reepithelialization of the ulcer. According to this finding, it is important to study the latex mechanism of action in the healing of ulcers in diabetic animals. Thus, the findings of NLB as inducing the healing by the stimulation of inflammatory phase (FRADE, 2003; ANDRADE, 2007), mainly by increasing the neutrophilic infiltrate in the area in healing; the effectiveness of the NLB healing diabetic ulcers (FRADE et al., 2004) connected with recent works of Goren et al., 2006 on the role of Oncostatin M also related to the influx of PMN in diabetic ulcers; it becomes relevant to the study of tissues modifications and mechanisms of signaling involved in the wound healing treated with the latex rubber tree Hevea brasiliensis in diabetic rats. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MORETTI ANDRADE, THIAGO ANTONIO; MASSON-MEYERS, DANIELA SANTOS; CAETANO, GUILHERME FERREIRA; TERRA, VANIA APARECIDA; OVIDIO, PAULA PAYAO; JORDAO-JUNIOR, ALCEU AFONSO; CIPRIANI FRADE, MARCO ANDREY. Skin changes in streptozotocin-induced diabetic rats. Biochemical and Biophysical Research Communications, v. 490, n. 4, p. 1154-1161, . (09/09355-0)
PEGORIN, GIOVANA S.; LEITE, MARCEL N.; ANTONIASSI, MARCIO; CHAGAS, ANA LAURA D.; SANTANA, LUISIANE A.; GARMS, BRUNA C.; MARCELINO, MONICA Y.; HERCULANO, RONDINELLI D.; CIPRIANI FRADE, MARCO ANDREY. Physico-chemical characterization and tissue healing changes by Hancornia speciosa Gomes latex biomembrane. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, v. 109, n. 7, . (17/19603-8, 09/09355-0, 16/16437-7)

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