title: Topical anti-inflammatory effect of hypocholesterolaemic drugs.
abstract: OBJECTIVE
  The topical anti-inflammatory effect of simvastatin, atorvastatin, pravastatin, ezetimibe and combined ezetimibe + simvastatin was investigated, using the croton oil model of ear oedema in mice.
  
  
  METHODS
  Simvastatin, atorvastatin, pravastatin, ezetimibe and ezetimibe + simvastatin combination (dissolved in 20 µl of 70% acetone) were topically applied simultaneously with croton oil (200 µg/ear, dissolved in 20 µl of 70% acetone) at the inner surface of each ear. Ear oedema and myeloperoxidase activity, indicative of polymorphonuclear cell migration, were assessed 6 h after inflammatory stimuli.
  
  
  RESULTS
  It was found that statins can act as topical anti-inflammatories, but the pharmacological effect is dependent on statin polarity. At 0.3 mg/ear inhibition of ear oedema was 79%, 67% and 40% for simvastatin, atorvastatin and pravastatin, respectively. Simvastatin and atorvastatin also remarkably diminished myeloperoxidase activity, even at low concentrations (0.03 mg/ear). Pravastatin, the most polar statin, however, did not cause any reduction in ear oedema or myeloperoxidase activity at low doses. The order of topical anti-inflammatory activity was pravastatin < < < atorvastatin ≤ simvastatin. Ezetimibe, another hypocholesterolaemic drug, also presented anti-inflammatory effects, inhibiting ear oedema by 64% at 0.3 mg/ear. However, when used in combination with simvastatin, no further beneficial effect was observed.
  
  
  CONCLUSIONS
  These results consistently support current evidence showing that statins can be used for treatment of dermatological disorders. Polarity of the molecule, however, is a factor that should be considered before recommending use.
authors.affiliation: Laboratory of Inflammation, Department of Pharmacy and Pharmacology, University of Maringá, Maringá, Paraná, Brazil.
authors.forename: Lívia
authors.initials: L
authors.lastname: Bracht
authors.forename: Silvana Martins
authors.initials: SM
authors.lastname: Caparroz-Assef
authors.forename: Thiago Ferreira dos Santos
authors.initials: TF
authors.lastname: Magon
authors.forename: Alessandra Mileni Versuti
authors.initials: AM
authors.lastname: Ritter
authors.forename: Roberto Kenji Nakamura
authors.initials: RK
authors.lastname: Cuman
authors.forename: Ciomar Aparecida
authors.initials: CA
authors.lastname: Bersani-Amado
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D003436:Croton Oil / Q000633:toxicity; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects* / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003436:Croton Oil; D019821:Simvastatin; D009195:Peroxidase