Effect of inhaled liposomal retinoids on the hyperoxia induced lung injury in newborn guinea pigs

Pharmacological approaches to prevent bronchopulmonary dysplasia (BPD) have been not developed yet. We used hyperoxia model of BPD to study the influence of inhaled liposomal retinoids on the lung morphology and lung tissue growth factors (TGFβ1, VEGF), neutrophil elastase and its inhibitor, α1-antitrypsin (A1-AT) in newborn guinea pigs. The studied groups: “hyperoxia” (n=10, 70% O 2 , 14 days), “hyperoxia+liposomes” (n=6, liposomes containing dipalmitoylphosphatidylcholine (45 mg/kg), retinol (6 mg/kg), retinoic acid (0,6 mg/kg) were introduced by nebulizer on alternate days on hyperoxia exposure), “control” (n=9, exposed to room air). Increased level of elastase and A1-AT (2,9-fold and 1,8-fold, respectively, p<0,05 versus controls), reduced VEGF (82% from controls, p<0,05) and unchanged TGFβ1 have been found in "hyperoxia" group. Lung sections demonstrated small-focal atelectases, parenchymal inflammatory cell infiltrates, decreased alveolar number and septa, increased area of alveolar spaces (11,7 (11,3 – 12,4) μm 2 versus 10,5 (10,3 – 10,7) μm 2 in controls, p<0,05). In “hyperoxia+liposomes” group growth factors in the lung tissue were not changed as compared to “hyperoxia”, elastase level decreased and did not differ significantly from the control group, the activity of A1-AT was 2,5-fold higher than in controls (p<0,05). Intraalveolar accumulation of macrophages was revealed (probably, in response to liposome introduction), however, lung morphometry data showed correspondence with the control group. Thus, inhaled liposomal retinoids improve elastase/A1-AT ratio and prevent the development of morphological changes in lungs of newborn guinea pigs exposed to prolonged hyperoxia.