title: Topical continuous use of Lippia sidoides Cham. essential oil induces cutaneous inflammatory response, but does not delay wound healing process.
abstract: BACKGROUND
  The essential oil of Lippia sidoides (EOLS) has been used in Brazilian folk medicine as a topical antiseptic agent in skin for treatment of wounds and superficial infections of the body. The aim of this study was to investigate the effects of EOLS on intact and damaged skin, including its action on expression of mediators, COX-2 and VEGF, involved in healing full-thickness cutaneous lesions in vivo.
  
  
  METHODS
  EOLS was analyzed chemically and used at different concentrations to dose-response experiments in skin mice. Skin irritation tests by one-dosage and multiple-dosages and irritation to damaged skin were assessed by macroscopy, morphometry and histological and immunohistochemical analyses. To evaluate the effects of EOLS on wound healing, excision wounds were surgically created on the dorsum of rats, and the ointments at 6% and 12% were applied daily to the wound area. Cutaneous lesions were assessed by planimetric (wound contraction) and macroscopic parameters.
  
  
  RESULTS
  Skin irritation tests showed that topical application of EOLS promoted cutaneous inflammation in varying degrees, which was demonstrated by increase of skin thickness and formation of cutaneous edema and erythema. Topical administration of EOLS in high concentrations presented an irritant response to skin, but this irritation is lighter when low concentrations this oil were used. Histological evaluation supported the outcome of these models, which revealed accentuated presence of inflammatory cells infiltration. In wound healing process, the lesions treated with EOLS showed intense edema and exsudation up to day 5, but there were not significant differences in the wound contraction on days 14 and 21. No immunohistochemical staining was verified to COX-2 and VEGF mediators in skin treated with EOLS 12%.
  
  
  CONCLUSIONS
  The continuous application of EOLS in adequate concentrations on cutaneous wounds increases inflammatory response without delay the lesions closure. The association of these results with antimicrobial action previously related to EOLS allows its indication as an alternative therapeutic modality for topical treatment of infected cutaneous wound. Nevertheless, further studies need to be performed to determine the mechanism of action and support its application in clinical practice.
authors.affiliation: Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará, Campus do Itaperi, CEP 60740-903 Fortaleza, Ceará, Brazil.
authors.forename: Maria Liduína Maia
authors.initials: ML
authors.lastname: de Oliveira
authors.affiliation: Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará, Campus do Itaperi, CEP 60740-903 Fortaleza, Ceará, Brazil.
authors.forename: Belise Maria Oliveira
authors.initials: BM
authors.lastname: Bezerra
authors.affiliation: Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará, Campus do Itaperi, CEP 60740-903 Fortaleza, Ceará, Brazil.
authors.forename: Luana Oliveira
authors.initials: LO
authors.lastname: Leite
authors.affiliation: Departamento de Morfologia, Faculdade de Medicina, Universidade Federal do Ceará, Campus do Porangabuçu, CEP 60430-170 Fortaleza, Ceará, Brazil.
authors.forename: Virgínia Cláudia Carneiro
authors.initials: VC
authors.lastname: Girão
authors.affiliation: Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará, Campus do Itaperi, CEP 60740-903 Fortaleza, Ceará, Brazil. Electronic address: diana.pinheiro@uece.br.
authors.forename: Diana Célia Sousa
authors.initials: DC
authors.lastname: Nunes-Pinheiro
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001938:Brazil; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D032411:Lippia / Q000737:chemistry*; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D009822:Oils, Volatile / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D009824:Ointments; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000473:pathology; D023422:Skin Irritancy Tests; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D009822:Oils, Volatile; D009824:Ointments; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2
keywords: Essential oil; Inflammation; Lippia sidoides; Skin; Verbenaceae; Wound healing