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  • 1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-κB activity in mice.

1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-κB activity in mice.

Life sciences (2013-05-25)
Patricia Rodrigues Lima, Tiago Sousa de Melo, Karine Maria Martins Bezerra Carvalho, Ítalo Bonfim de Oliveira, Bruno Rodrigues Arruda, Gerly Anne de Castro Brito, Vietla Satyanarayana Rao, Flávia Almeida Santos
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Eucalyptol, 99%
Sigma-Aldrich
Caerulein, ≥95% (HPLC)
Supelco
Eucalyptol, analytical standard
Supelco
1,8-Cineole, primary reference standard
Sigma-Aldrich
Eucalyptol, natural, ≥99%, FCC, FG
Cineole, European Pharmacopoeia (EP) Reference Standard
Supelco
Eucalyptol, certified reference material, TraceCERT®