title: 1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-κB activity in mice.
abstract: OBJECTIVE
  Acute pancreatitis (AP) is an inflammatory condition wherein pro-inflammatory mediators, oxidative stress, and NF-κB signaling play a key role. Currently, no specific therapy exists and treatment is mainly supportive and targeted to prevent local pancreatic injury and systemic inflammatory complications. This study was aimed to examine whether 1,8-cineole, a plant monoterpene with antioxidant and anti-inflammatory properties could ameliorate cerulein-induced acute pancreatitis.
  
  
  METHODS
  AP was induced in Swiss mice by six one hourly injections of cerulein (50 μg/kg, i.p.). 1,8-cineole (100, 200 and 400mg/kg, p.o.) was administered 1h prior to first cerulein injection, keeping vehicle and thalidomide treated groups as controls. Blood samples were taken 6-h later to determine serum levels of amylase and lipase, and cytokines. The pancreas was removed for morphological examination, myeloperoxidase (MPO) and malondialdehyde (MDA) assays, reduced glutathione (GSH) levels, and for nuclear factor (NF)-κB immunostaining.
  
  
  RESULTS
  1,8-cineole effectively reduced the cerulein-induced histological damage, pancreatic edema and NF-κB expression, levels of MPO activity and MDA, and replenished the GSH depletion. Cerulein increased serum levels of amylase and lipase, and pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were also decreased by 1,8-cineole pretreatment, similar to thalidomide, a TNF-α inhibitor. The anti-inflammatory IL-10 cytokine level was, however, enhanced by 1,8-cineole.
  
  
  CONCLUSIONS
  These findings indicate that 1,8-cineole can attenuate cerulein-induced AP via an anti-inflammatory mechanism and by combating oxidative stress. Further studies are needed to clearly elucidate its benefits in patients on acute pancreatitis.
authors.affiliation: Post-Graduate Programme in Medical Sciences, Faculty of Medicine, Federal University of Ceará, 60430-140 Fortaleza, Ceará, Brazil.
authors.forename: Patricia Rodrigues
authors.initials: PR
authors.lastname: Lima
authors.forename: Tiago Sousa
authors.initials: TS
authors.lastname: de Melo
authors.forename: Karine Maria Martins Bezerra
authors.initials: KM
authors.lastname: Carvalho
authors.forename: Ítalo Bonfim
authors.initials: ÍB
authors.lastname: de Oliveira
authors.forename: Bruno Rodrigues
authors.initials: BR
authors.lastname: Arruda
authors.forename: Gerly Anne
authors.initials: GA
authors.lastname: de Castro Brito
authors.forename: Vietla Satyanarayana
authors.initials: VS
authors.lastname: Rao
authors.forename: Flávia Almeida
authors.initials: FA
authors.lastname: Santos
mesh_terms: D000818:Animals; D002108:Ceruletide / Q000633:toxicity*; D003511:Cyclohexanols / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism* / Q000502:physiology; D000077591:Eucalyptol; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*
chemical_list: D003511:Cyclohexanols; D016207:Cytokines; D039821:Monoterpenes; D016328:NF-kappa B; D002108:Ceruletide; D000077591:Eucalyptol