Topical Delivery of 13-cis-Retinoic Acid by Inhalation Up-Regulates Expression of Rodent Lung but not Liver Retinoic Acid Receptors

摘要: Chemopreventive retinoids may be more effective if delivered to the lung epithelium by inhalation. 13- cis -Retinoic acid (13- -RA) was comparable all- trans -retinoic (RA) in inducing transglutaminase II (TGase II) cultured human cells. Inhaled -RA had a significant stimulatory activity on TGase rat ( P < 0.001) but not liver tissue 0.544). Furthermore, inhaled at daily deposited doses of 1.9 mg/kg/day up-regulated expression retinoic receptors (RARs) α,β , and γ day 1 (RARα 3.4-fold, RARβ 7.2-fold, RARγ 9.7-fold) 17 4.2-fold, 10.0-fold, 12.9-fold). At lower aerosol concentration, 0.6 were also 28 days. Lung RARα induced 4.7-fold, 8.0-fold, 8.1-fold. Adjustment dose exposure duration effective; thus, inhalation an concentration 62.2 μg/liter, for durations from 5 240 min 14 days, all RARs 30.6- 74-fold shortest time. None animals exposed aerosols showed RAR induction livers. By contrast, diet containing pharmacological RA (30 μg/g diet) failed induce SENCAR mouse lung, although it (RARα, 21.8-fold; RARβ, 13.5-fold; RARγ, 12.5-fold); II. A striking increase evident nuclei hepatocytes. Pharmacological dietary stimulated RARα, as early 2-, 4-, 2.1-fold, respectively, without effect RARs. Therefore, rats is potent stimulant Conversely, stimulates These data support concept that epithelial delivery chemopreventive efficacious way attain up-regulation retinoid possibly achieve chemoprevention.