Inhalation of an ethanol-based zileuton formulation provides a reduction of pulmonary adenomas in the A/J mouse model

Abstract

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.

Fig. 1

Chemical structure of zileuton

Fig. 2

Particle size data for zileuton solutions administered five times a week (filled squares) and twice a week (filled triangles). Solid symbols depict MMAD, while outlined symbols represent GSD

Fig. 3

Negative control (top left) depicts what normal alveolar space looks like in the A/J mouse lung. The other three pictures are representative adenomas observed in zileuton five times a week (top right), positive control (bottom left), and solution placebo (bottom right). Magnification at ×100

Fig. 4

Relative percent composition for each group as a function of total tumor count within each group