Inhalation of an Ethanol-Based Zileuton Formulation Provides a Reduction of Pulmonary Adenomas in the A/J Mouse Model
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Potential efficacy of zileuton, a 5-LOX inhibitor, was evaluated for the reduction of pulmonary adenomas in the A/J murine model when administered via nose-only inhalation. Development of pulmonary adenomas was induced with benzo(a)pyrene. Animals were treated with a zileuton solution (5 mg/mL in 85:15 ethanol/water) either twice weekly or five times a week via nose-only inhalation; The placebo solution (85:15 EtOH/H2O, no active) was also evaluated. Dose delivered was calculated to be 1.2 mg/kg per exposure for each zileuton group. After 20 weeks of treatment, surface tumors were enumerated and histologically assessed. A significant reduction in tumor count was noted for both the twice weekly administration (40%) and the five times a week administration (59%). The data also showed a significant reduction for the group, which received the placebo (approximately 58%). The treatment groups were also found to have an impact on the histological stages of adenoma development.
Key wordsaerosol chemoprevention ethanol lung cancer zileuton
This research study was funded by the Arizona Biomedical Research Commission, Grant no. 5-082.
- 1.American Cancer Society. Cancer Reference Information [Internet]. c2009 [cited 2009 Jun 8]. http://www.cancer.org/docroot/CRI/content.
- 3.Gagnadoux F, Hureaux J, Vecellio L, Urban T, Le Pape A, Valo I, et al. Aerosolized chemotherapy. J Aerosol Med. 2008;21(1):1–9.Google Scholar
- 10.Carter GW, Young PR, Albert DH, Bouska J, Dyer R, Bell RL, et al. 5-Lipoxygenase inhibitory activity of Zileuton. J Pharm Exp Thera. 1991;256(3):929–37.Google Scholar
- 15.Wattenberg LW, Wiedmann TS, Zimmerman CL, Galbraith AR, Steele VE, Kelloff GJ. Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone diproprionate and by the combination of aerosolized budesonide and dietary myo-inositol. Carcinogenesis. 2000;21:179–82.CrossRefPubMedGoogle Scholar
- 16.Alexander DJ, Collins CJ, Coombs DW, Gilkison IS, Hardy CJ, Healey G, et al. Association of inhalation toxicologists (AIT) working party recommendation for standards delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals. Inhal Toxicol. 2008;20:1179–89.CrossRefPubMedGoogle Scholar
- 18.Dungworth DL, Rittinghausen S, Schwartz L, Harkema JR, Hayashi Y, Killel B, et al. Respiratory system and mesothelium. In: Mohr U, editor. International classification of rodent tumors: the mouse. Germany: Springer; 2001. p. 87–138.Google Scholar
- 25.Altmann H-J, Dusemond B, Goll M, Grunow W. Effect of ethanol on the induction of lung tumors by ethyl carbamate in mice. Toxicology. 2005;43:1–19.Google Scholar
- 26.Djousee L, Dorgan JF, Zhang Y, Schatzkin A, Hood M, D’Agostino RB, et al. Alcohol consumption and risk of lung cancer: the Framingham study. J Natl Cancer Inst. 2002;94(24):1877–82.Google Scholar
- 29.Stoewsand GS, Anderson JL, Munson L. The role of wine in ethyl carbamate induced carcinogenesis inhibition. ACS Symposium Series. 1997;661:220–36.Google Scholar
- 32.Yum S, Lee E, Taskovich L, Theeuwes F. Permeation enhancement with ethanol: mechanism of action through the skin. Drugs Pharmaceut Sci. 1994;62:143–70.Google Scholar