Comparative Study of Unfractionated Heparins and Low Molecular Weight Heparin on Skin Wound Repair
Natália Lopes Viana
Biology Institute, State University of Campinas, Campinas-SP, 13083-862, Brazil and Biomedical Sciences Institute, Federal University of Uberlândia, Uberlândia-MG, 38400-902, Brazil.
Francyelle Borges Rosa de Moura
Biomedical Sciences Institute, Federal University of Uberlândia, Uberlândia-MG, 38400-902, Brazil and Biology Institute, Federal University of Catalão-GO, 75704-020, Brazil.
José Augusto Leoncio Gomide
Biotechnology Institute, Federal University of Uberlândia, Uberlândia-MG, 38405-319, Brazil.
Bruno Antonio Ferreira
Biotechnology Institute, Federal University of Uberlândia, Uberlândia-MG, 38405-319, Brazil.
Elusca Helena Muniz
Biomedical Sciences Institute, Federal University of Uberlândia, Uberlândia-MG, 38400-902, Brazil.
Fernanda de Assis Araújo
Biomedical Sciences Institute, Federal University of Uberlândia, Uberlândia-MG, 38400-902, Brazil.
Daniele Lisboa Ribeiro
Biomedical Sciences Institute, Federal University of Uberlândia, Uberlândia-MG, 38400-902, Brazil.
Mauro Sérgio Gonçalves Pavão
Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro-RJ, 21941-902, Brazil.
Edson Rosa Pimentel
Biology Institute, State University of Campinas, Campinas-SP, 13083-862, Brazil.
Tatiana Carla Tomiosso *
Biomedical Sciences Institute, Federal University of Uberlândia, Uberlândia-MG, 38400-902, Brazil.
*Author to whom correspondence should be addressed.
Abstract
Aims: Heparin (HP) has aroused interest in the treatment of skin wounds. The HP extraction sources and the chemical diversity of its structural chain result in different clinical responses. In this study, a comparison was made among the effects of unfractionated heparin from bovine (bovHP) and swine (swi.HP) sources and low molecular weight heparin (LMWH) on skin lesions treatment.
Study Design: Wounds were induced on the back of Swiss mice using a punch. Then, the wounds were treated with heparins for 3 and 7 days.
Place and Duration of Study: Institute of Biomedical Sciences and Animal Breeding Network and Rodents of the Federal University of Uberlândia, between April 2018 and February 2020.
Methodology: Wound closure was performed with a digital caliper. The inflammatory infiltrate was assessed by the activity of neutrophils and macrophages. Angiogenesis was measured by quantifying blood vessels and measuring hemoglobin. While fibrogenesis was assessed by picrosirius red staining.
Results: None of the heparins had a healing effect. Swi.HP showed delay in wound closure and intensification of the inflammatory process compared to bov.HP. Swine and bovine heparins showed pro-angiogenic activity, although this did not differ between them. Difference between the groups of heparins was observed in relation to the deposition and organization of collagen fibers, with a reduction in fibrogenesis in wounds of the LMWH group compared to the other heparins, especially bov.HP. A better fibrogenic activity was observed for bov.HP.
Conclusion: Thus, we conclude that the source of the heparin used should be considered, as its pharmacological response for wound treatment is quite diverse. Although none of the heparins was able to accelerate wound closure, bov.HP had an anti-inflammatory and pro- fibrogenic effect compared to the other heparins and therefore showed the best response in this experimental model.
Keywords: Bovine heparin, collagen, glycosaminoglycan, healing, porcine heparin