Eucalyptol attenuates cigarette smoke-induced acute lung inflammation and oxidative stress in the mouse.
Short-term cigarette smoke (CS) exposure does not cause emphysema; however, some pathogenesis hallmarks are maintained, such as oxidative stress and inflammation. This study aimed to test the efficacy of eucalyptol against short-term CS exposure in mice. C57BL/6 mice were exposed to 12 cigarettes per day for 5 days (CS group). The control group was exposed to sham smoking. Three groups of mice exposed to CS were treated to different concentrations of eucalyptol (1, 3, 10 mg/mL) via inhalation (15 min/daily) for 5 days (CS + 1 mg, CS+3 mg and CS+10 mg groups). CS group and control one were sham treated by using vehicle. The anti-inflammatory and antioxidant effects of eucalyptol were assessed 24 h after the last CS exposure by determining cell counts, measuring cytokine production and performing western blotting, biochemical and histological analyses. Eucalyptol at 3 mg/mL and 10 mg/mL concentrations reduced total leukocyte numbers compared to the CS group (p < 0.001), while macrophage numbers were reduced at all concentrations (p < 0.001). Myeloperoxidase, used as neutrophil marker, was reduced at 3 mg/mL (p < 0.01) and 10 mg/mL (p < 0.05) concentrations. Eucalyptol reduced cytokine levels (IL-1β, IL-6 and KC) at 3 mg/mL and 10 mg/mL concentrations (p < 0.01) compared to the CS group. The exception was TNF-α, with a reduction only at 10 mg/mL of eucalyptol compared to the CS group (p < 0.001). Additionally, eucalyptol decreased the NF-kappa B p65 subunit at 3 mg/mL and 10 mg/mL compared to the CS group (p < 0.01). Regarding oxidative stress, eucalyptol reduced reactive oxygen species, superoxide dismutase, catalase and malondialdehyde, mainly at 3 mg/mL and 10 mg/mL concentrations compared to the CS group (at least p < 0.05), parallel to reduced glutathione levels at the same concentrations (p < 0.001). Furthermore, treatment with eucalyptol attenuated CS-induced histopathological alterations. Collectively, these results indicate that eucalyptol acts through a mechanism involving decreased oxidative stress, inflammation and the NF-kappa B p65 subunit against CS-induced acute lung inflammation. Thus, eucalyptol may be a potential agent in the treatment of pulmonary inflammation caused by CS in humans.
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Emanuel
E
Kennedy-Feitosa
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Renata Tiemi
RT
Okuro
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Vanessa
V
Pinho Ribeiro
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Manuella
M
Lanzetti
Programa de Pós-graduação em Imunologia e Inflamação, Instituto de Microbiologia Paulo de Goés, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Marina Valente
MV
Barroso
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Walter Araújo
WA
Zin
Programa de Pós-graduação em Biologia Humana e Experimental, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Luís Cristóvão
LC
Porto
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Lycia
L
Brito-Gitirana
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: samuelv@ufrj.br.
Samuel Santos
SS
Valenca
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077591:Eucalyptol; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003511:Cyclohexanols; D039821:Monoterpenes; D017382:Reactive Oxygen Species; D012906:Smoke; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D000077591:Eucalyptol
Cigarette smoke; Eucalyptol; Inflammation; Oxidative stress