Inhibition of tobacco smoke-induced lung inflammation by a catalytic antioxidant.
Cigarette smokers experience airway inflammation and epithelial damage, the mechanisms of which are unknown. One potential cause may be free radicals either in tobacco smoke or produced during persistent inflammation. Inflammation may also be a driving force to cause airway epithelium to undergo changes leading to squamous cell metaplasia. To test whether tobacco smoke-induced inflammation could be reduced by a catalytic antioxidant, manganese(III)meso-tetrakis(N,N'-diethyl-1,3-imidazolium-2-yl) porphyrin (AEOL 10150) was given by intratracheal instillation to rats exposed to filtered air or tobacco smoke. Exposure to tobacco smoke for 2 d or 8 weeks (6 h/d, 3 d/week) significantly increased the number of cells recovered by bronchoalveolar lavage (BAL). AEOL 10150 significantly decreased BAL cell number in tobacco smoke-treated rats. Significant reductions in neutrophils were noted at 2 d and macrophages at 8 weeks. Lymphocytes were significantly reduced by AEOL 10150 at both time points. Squamous cell metaplasia following 8 weeks of tobacco smoke exposure was 12% of the total airway epithelial area in animals exposed to tobacco smoke without AEOL 10150, compared with 2% in animals exposed to tobacco smoke, but treated with AEOL 10150 (p <.05). We conclude that a synthetic catalytic antioxidant decreased the adverse effects of exposure to tobacco smoke.
Smith
Kevin R
KR
Center for Health and the Environment, University of California, Davis, CA 95616, USA. krsmith@ucdavis.edu
Uyeminami
Dale L
DL
Kodavanti
Urmila P
UP
Crapo
James D
JD
Chang
Ling-Ying
LY
Pinkerton
Kent E
KE
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002248:Carbon Monoxide / Q000097:blood; D002384:Catalysis / Q000187:drug effects; D002452:Cell Count; D019743:Chemokines, CXC; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D007322:Instillation, Drug; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D018655:Lymphocyte Count; D008264:Macrophages / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D008679:Metaplasia; D015846:Monokines / Q000032:analysis; D009504:Neutrophils / Q000473:pathology; D009538:Nicotine / Q000097:blood; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014132:Trachea
C472668:AEOL 10150; D000975:Antioxidants; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D008665:Metalloporphyrins; D015846:Monokines; D017382:Reactive Oxygen Species; D012906:Smoke; D014028:Tobacco Smoke Pollution; D018799:Intercellular Adhesion Molecule-1; D009538:Nicotine; D002248:Carbon Monoxide