title: Effects of All trans-Retinoic Acid on Alveolar Regeneration in Dexamethasone-Induced Emphysema Models and Its Relationship to Exposure in ICR and FVB Mice.
abstract: During the past two decades, it has been reported that treatment with all-trans-retinoic acid (ATRA) induces alveolar regeneration in rodent emphysema models. In the present study, we investigated the regeneration by ATRA at various exposure conditions in two strains of mice with induced emphysema. The emphysema model was created by postnatal administration of dexamethasone to ICR and FVB mice, which were then treated with ATRA from postnatal day 42. The regeneration was observed in ICR mice but not in FVB mice given 10 and 40 mg/kg/d ATRA for 10 d. The concentration-time profiles of ATRA in plasma and lung were similar in both strains. These results suggest that the strain difference in the regeneration by ATRA was not caused by differences in the exposure to ATRA. On the other hand, the regeneration in ICR mice was enhanced by an increase of the intraperitoneal dose in the range of 10-40 mg/kg/d for 10 d. At an intraperitoneal dose of 40 mg/kg/d, the regeneration was observed after 10 and 20 d of treatment but not after 1 to 5 d of treatment. Meanwhile, the regeneration by intraperitoneal administration of ATRA was enhanced more than that by oral administration. Exposure to ATRA during repeated intraperitoneal administration to ICR mice was higher than that in oral administration. The results suggest that the regeneration in ICR mice requires at least 10 d of treatment with ATRA and its effects depend on the exposure to ATRA in plasma, which parallels that in lung.
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohashi
authors.forename: Anri
authors.initials: A
authors.lastname: Fujishiro
authors.forename: Yuka
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Ayumi
authors.initials: A
authors.lastname: Hiramatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirota
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003907:Dexamethasone; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008297:Male; D008813:Mice, Inbred ICR; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012038:Regeneration / Q000187:drug effects*; D014212:Tretinoin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D014212:Tretinoin; D003907:Dexamethasone