title: All-trans-retinoic acid (ATRA) is of no benefit in bleomycin-induced lung injury.
abstract: All-trans-retinoic acid (ATRA) has anti-fibrotic and antiinflammatory properties, and may be useful as a therapeutic agent in lung fibrosis. To test this hypothesis we investigated the effect of ATRA on bleomycin-induced lung fibrosis in Sprague-Dawley rats. Treatment groups included: (1) a single intratracheal (i.t.) instillation of bleomycin and daily intraperitoneal (i.p.) injection of 0.5 mg/kg per day ATRA; (2) i.t. bleomycin and i.p. ATRA, 2 mg/kg per day, (3) i.t. bleomycin and i.p. diluent (cottonseed oil); (4) i.t. saline and i.p. ATRA, 0.5 mg/kg per day, (5) i.t. saline and i.p. ATRA, 2 mg/kg per day; and (6) i.t. saline and i.p. diluent. Animals were studied 14 days after i.t. instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semi-quantitative morphological index of lung injury, and by biochemical analysis of lung hydroxyproline content. Overt signs of lung injury were apparent in bleomycin-treated rats by all measures. These changes were not affected by treatment with ATRA at either dose. This study does not support the use of ATRA to prevent or ameliorate lung fibrosis.
authors.affiliation: Lung Cellular & Molecular Biology Laboratory, Institute of Pulmonology, Hadassah University Hospital, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
authors.forename: M J
authors.initials: MJ
authors.lastname: Segel
authors.forename: R
authors.initials: R
authors.lastname: Or
authors.forename: A
authors.initials: A
authors.lastname: Tzurel
authors.forename: E C
authors.initials: EC
authors.lastname: Lucey
authors.forename: R H
authors.initials: RH
authors.lastname: Goldstein
authors.forename: G
authors.initials: G
authors.lastname: Izbicki
authors.forename: R
authors.initials: R
authors.lastname: Breuer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001761:Bleomycin / Q000009:adverse effects*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000517:prevention & control* / Q000662:veterinary; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001761:Bleomycin; D014212:Tretinoin