Inhalation of an ethanol-based zileuton formulation provides a reduction of pulmonary adenomas in the A/J mouse model.
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.
Karlage
Kelly L
KL
College of Pharmacy, University of Arizona, 1703 E. Mabel St, Tucson, Arizona 85721, USA. karlage@pharmacy.arizona.edu
Mogalian
Erik
E
Jensen
Annikka
A
Myrdal
Paul B
PB
D000236:Adenoma / Q000473:pathology*; D000280:Administration, Inhalation; D000818:Animals; D001564:Benzo(a)pyrene; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D000431:Ethanol; D005260:Female; D006918:Hydroxyurea / Q000031:analogs & derivatives; D001239:Inhalation; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008805:Mice, Inbred A
D004304:Dosage Forms; D001564:Benzo(a)pyrene; D000431:Ethanol; C063449:zileuton; D006918:Hydroxyurea