title: Effect of atorvastatin on wound healing in rats.
abstract: Skin-wound healing is a complex and dynamic biological process involving inflammation, proliferation, and remodeling. Recent studies have shown that statins are new therapeutical options because of their actions, such as anti-inflammatory and antioxidant activity, on vasodilation, endothelial dysfunction and neoangiogenesis, which are independent of their lipid-lowering action. Our aim was to investigate the effect of atorvastatin on tissue repair after acute injury in healthy animals. Rats were divided into four groups: placebo-treated (P), topical atorvastatin-treated (AT), oral atorvastatin-treated (AO), topical and oral atorvastatin-treated (ATO). Under anesthesia, rats were wounded with an 8-mm punch in the dorsal region. Lesions were photographed on Days 0, 1, 3, 7, 10, 12, and 14 post-injury and samples taken on Days 1, 3, 7, and 14 for protein-expression analysis of insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase (GSK)-3, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK), interleukin (IL)-10, IL-1β, IL-6, and tumor necrosis factor (TNF)-α. Upon macroscopic examination, we observed significant reductions of lesion areas in groups AT, AO, and ATO compared to the P group. Additionally, AT and AO groups showed increased expression of IRS-1, PI3K, Akt, GSK-3, and IL-10 on Days 1 and 3 when compared with the P group. All atorvastatin-treated groups showed higher expression of IRS-1, PI3K, Akt, GSK-3, IL-10, eNOS, VEGF, and ERK on Day 7. On Days 1, 3, and 7, all atorvastatin-treated groups showed lower expression of IL-6 and TNF-α when compared with the P group. We conclude that atorvastatin accelerated tissue repair of acute lesions in rats and modulated expressions of proteins and cytokines associated with cell-growth pathways.
authors.affiliation: Faculty of Nursing, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Vanessa Ferraz
authors.initials: VF
authors.lastname: Suzuki-Banhesse
authors.affiliation: Faculty of Nursing, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Flávia Figueiredo
authors.initials: FF
authors.lastname: Azevedo
authors.affiliation: Faculty of Nursing, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Eliana Pereira
authors.initials: EP
authors.lastname: Araujo
authors.affiliation: Herminio Ometto University Center (UNIARARAS), Araras, São Paulo, Brazil.
authors.forename: Maria Esméria Corezola
authors.initials: ME
authors.lastname: do Amaral
authors.affiliation: Institute of Biomedical Sciences, University of Sao Paulo (USP), São Paulo, Brazil.
authors.forename: Andrea Moro
authors.initials: AM
authors.lastname: Caricilli
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Mario Jose Abdalla
authors.initials: MJ
authors.lastname: Saad
authors.affiliation: Faculty of Nursing, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil mhmelolima@gmail.com.br.
authors.forename: Maria Helena Melo
authors.initials: MH
authors.lastname: Lima
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000069059:Atorvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015151:Immunoblotting; D016753:Interleukin-10 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis; D058539:Phosphatidylinositol 3-Kinase / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D051381:Rats; D011972:Receptor, Insulin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C052994:interleukin-1beta (163-171); D016753:Interleukin-10; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; D058539:Phosphatidylinositol 3-Kinase; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3
keywords: hydroxymethylglutaryl-CoA reductase inhibitors; nursing; wound healing