title: Effects of Kaurenoic Acid and Arginine on Random Skin Flap Oxidative Stress, Inflammation, and Cytokines in Rats.
abstract: BACKGROUND
  Kaurenoic acid (KA), a diterpene extracted from copaíba oil-resin, is known to have potent antioxidant and anti-inflammatory properties. L-Arginine (LA) is an amino acid and a nitrogenous precursor for the synthesis of nitric oxide (NO). NO paper in wound healing has already been well documented. The aim of this study was to investigate the protective effects of LA and KA against ischemia reperfusion injury in a randomized skin flap model in rats.
  
  
  METHODS
  A modified McFarlane flap model measuring 2.5 wide × 8 cm long was established in 36 anesthetized rats and evaluated within 3 groups: group control, group L-arginine, and group kaurenoic acid. Each group was subdivided into two subgroups (T1 and T2, n = 6 each). Samples were collected 24 h (T1)/48 h (T2) postoperatively for oxidative stress (glutathione), as non-protein thiols, malondialdehyde (MDA), NO2, inflammation [myeloperoxidase (MPO)], and cytokines TNF-α and IL-1β assays.
  
  
  RESULTS
  KA promoted a significant decrease of TNF-α and IL-1 expression and MPO activity at T1/T2 time points. NSGH levels increased significantly in KA-treated rats, while MDA levels decreased significantly in the same rats. Arginine promoted a significant decrease in MDA levels at the T1 time point and a significant increase in non-protein thiols concentrations at T1/T2 time points. NO2 concentration also decreased at the T1 time point.
  
  
  CONCLUSIONS
  KA may attenuate the oxidative stress and the inflammation, thereby reducing tissue damage induced by ischemia/reperfusion in rats subjected to dorsal skin flaps.
  
  
  METHODS
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authors.affiliation: Department of Surgery, Federal University of Ceará (UFC), Rua Professor Costa Mendes, 1608/3º andar, Bloco Didático, Fortaleza, CE, 60430-140, Brazil. cirurgiaoplastico@joaquimjose.med.br.
authors.forename: Joaquim José de Lima
authors.initials: JJ
authors.lastname: Silva
authors.affiliation: Course of Chemical Engineering (UFC), Av. da Universidade, 2853 - Benfica, Fortaleza, CE, 60020-181, Brazil. deboragpompeu@gmail.com.
authors.forename: Débora Gramosa
authors.initials: DG
authors.lastname: Pompeu
authors.affiliation: Faculty of Pharmacy, Dentistry and Nursing (UFC), Rua Alexandre Baraúna, 949 - Rodolfo Teófilo, Fortaleza, CE, 60430-160, Brazil. naiaracx@gmail.com.
authors.forename: Naiara Coelho
authors.initials: NC
authors.lastname: Ximenes
authors.affiliation: Department of Morphology (UFC), Rua Delmiro de Farias s/n - Rodolfo Teófilo, Fortaleza, CE, 60416-030, Brazil. asouzagomes@yahoo.com.br.
authors.forename: Antoniella Souza Gomes
authors.initials: AS
authors.lastname: Duarte
authors.affiliation: Department of Organic and Inorganic Chemistry (UFC), Campus do Pici, bloco 940 Bairro Pici, Fortaleza, CE, 60451-970, Brazil. nilcegramosapompeu@yahoo.com.br.
authors.forename: Nilce Viana
authors.initials: NV
authors.lastname: Gramosa
authors.affiliation: Clinical Pharmacology and Molecular Laboratory, School of Medicine, Ceara State University (UECE), Av. Dr. Silas Muguba, 1700 - Campus do Itaperi, Fortaleza, CE, 60740-000, Brazil. carvalhokris@gmail.com.
authors.forename: Krishnamurti de Morais
authors.initials: Kde M
authors.lastname: Carvalho
authors.affiliation: Department of Morphology (UFC), Rua Delmiro de Farias s/n - Rodolfo Teófilo, Fortaleza, CE, 60416-030, Brazil. gerlybrito@hotmail.com.
authors.forename: Gerly Anne de Castro
authors.initials: GA
authors.lastname: Brito
authors.affiliation: Department of Surgery, Federal University of Ceará (UFC), Rua Professor Costa Mendes, 1608/3º andar, Bloco Didático, Fortaleza, CE, 60430-140, Brazil. sergiobotelho@terra.com.br.
authors.forename: Sergio Botelho
authors.identifier: http://orcid.org/0000-0002-3837-234X
authors.initials: SB
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects* / Q000502:physiology*; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D013524:Surgical Flaps
chemical_list: D016207:Cytokines; D004224:Diterpenes; C051436:kaurenoic acid; D001120:Arginine
keywords: Cutaneous flaps; Inflammatory response; Kaurenoic acid; L-Arginine; Oxidative stress; Rats; Wistar