Aspirin and indomethacin reduce lung inflammation of mice exposed to cigarette smoke.
Neutrophil accumulation response to cigarette smoke (CS) in humans and animal models is believed to play an important role in pathogenesis of many tobacco-related lung diseases. Here we evaluated the lung anti-inflammatory effect of aspirin and indomethacin in mice exposed to CS. C57BL/6 mice were exposed to four cigarettes per day during 4 days and were treated i.p. with aspirin or indomethacin, administered each day 1h before CS exposure. Twenty four hours after the last exposure, cells and inflammatory mediators were assessed in bronchoalveolar lavage (BAL) fluid and the lungs used for evaluation of lipid peroxidation, p38 mitogen-activated protein kinase (MAPK) phosphorylation and nuclear transcription factor kappaB (NF-kappaB) activation. Exposure to CS resulted in a marked lung neutrophilia. Moreover, the levels of oxidative stress-related lipid peroxidation, prostaglandin E(2) (PGE(2)), interleukin 1beta (IL-1beta), monocyte chemotactic protein 1 (MCP-1), and activated NF-kappaB and p38 MAPK were greatly increased in CS group. Aspirin or indomethacin treatment led to a significant reduction of neutrophil influx, but only aspirin resulted in dramatic decrease of inflammatory mediators. Moreover, both drugs reduced lung p38 MAPK and NF-kappaB activation induced by CS. These results demonstrate that short-term CS exposure has profound airway inflammatory effects counteracted by the anti-inflammatory agents aspirin and indomethacin, probably through COX-dependent and -independent mechanisms.
Castro
Paulo
P
Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Brazil.
Nasser
Helena
H
Abrahão
Agessandro
A
Dos Reis
Larissa Cardilo
LC
Riça
Ingred
I
Valença
Samuel S
SS
Rezende
Daniele C
DC
Quintas
Luis E M
LE
Cavalcante
Moisés C Marinho
MC
Porto
Luis Cristóvão
LC
Koatz
Vera Lucia G
VL
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products
D012906:Smoke; D001241:Aspirin; D007213:Indomethacin