title: Evaluating the Effect of 3% Papain Gel Application in Cutaneous Wound Healing in Mice.
abstract: While the US Food and Drug Administration has not approved the use of 3% papain gel in the United States, the authors feel this study adds to the literature regarding its use.
  
  
  BACKGROUND
  The aim of this study was to evaluate the effect of 3% papain gel on wounds in mice.
  
  
  METHODS
  Thirty healthy C57BL mice (25-30 g) aged 10 weeks were randomly divided into 2 groups: mice treated with 3% papain gel and mice treated with placebo gel. Skin incisions were performed with a 6-mm metallic punch with a cutting blade edge. On days 3 and 7 after creating the lesion, the mice were euthanized and lesion samples were collected. The lesion samples were processed and sectioned into 3 fragments of skin to be stained with 3 types of dye: hematoxylin and eosin, Picrosirius red, and Weigert. In addition, immunohistochemical analysis (α-SM actin and Ki67) followed by real-time polymerase chain reaction (PCR) protocol was performed on the samples.
  
  
  RESULTS
  On gross examination, the 3% papain-treated group took less time to heal the wounds compared with the control. On day 7, microscopic examination showed the 3% papain-treated group had lower numbers of inflammatory cells, increased neovascularization, and improved organization of collagen and elastic fibers. Using PCR analysis, the 3% papain-treated group showed a significant increase in transforming growth factor beta and interleukin-6 expression compared with the control (P < .05).
  
  
  CONCLUSIONS
  Due to a reduced local inflammatory response, increased angiogenesis, and improved organization of collagen deposition, these findings demonstrate 3% papain gel can improve cutaneous wound healing in mice.
authors.affiliation: State University of Campinas, School of Nursing, São Paulo, Brazil.
authors.forename: Flávia
authors.initials: F
authors.lastname: Figueiredo Azevedo
authors.affiliation: State University of Campinas, School of Nursing, São Paulo, Brazil.
authors.forename: Letícia P
authors.initials: LP
authors.lastname: Santanna
authors.affiliation: State University of Campinas, School of Nursing, São Paulo, Brazil.
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Bóbbo
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Edson A
authors.initials: EA
authors.lastname: Libert
authors.affiliation: State University of Campinas, School of Nursing, São Paulo, Brazil.
authors.forename: Eliana P
authors.initials: EP
authors.lastname: Araújo
authors.affiliation: Department of Internal Medicine, FCM, State University of Campinas.
authors.forename: Mário
authors.initials: M
authors.lastname: Abdalla Saad
authors.affiliation: State University of Campinas, School of Nursing, São Paulo, Brazil.
authors.forename: Maria Helena M
authors.initials: MHM
authors.lastname: Lima
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D006097:Granulation Tissue / Q000473:pathology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010206:Papain / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D003094:Collagen; D010206:Papain