Safety and Preclinical Efficacy of Aerosol Pioglitazone on Lung Adenoma Prevention in A/J Mice

We examined the animals for any physical toxicity and bronchoalveolar lavage fluids for inflammatory and cytotoxicity markers. Doses up to and including 450 μg/kg bw/d failed to demonstrate toxicity with aerosol pioglitazone. For chemoprevention experiments, A/J mice were randomized to treatment groups of inhaled doses of 0, 50, 150, or 450 μg/kg bw/d pioglitazone 1 or 8 weeks after the last dose of B[a]P. For the early treatment group, we found up to 32% decrease in lung adenoma formation with 450 μg/kg bw/d pioglitazone. We repeated the treatments in a second late-stage experiment and found up to 44% decreases in lung adenoma formation in doses of pioglitazone of 150 and 450 μg/kg bw/day. Both the early- and the late-stage experiments demonstrated biologically relevant and statistically significant decreases in adenoma formation. We conclude that aerosol pioglitazone is well-tolerated in the A/J mouse model and a promising chemoprevention agent for the lower respiratory tract. Cancer Prev Res; 10(2); 124–32. ©2016 AACR.

Source: Cancer Prevention Research - February 1, 2017 Category: Cancer & Oncology Authors: Seabloom, D. E., Galbraith, A. R., Haynes, A. M., Antonides, J. D., Wuertz, B. R., Miller, W. A., Miller, K. A., Steele, V. E., Suen, C. S., O'Sullivan, M. G., Ondrey, F. G. Tags: Research Articles Source Type: research