Histopathological and biochemical effects of prophylactic vitamin a and isotretinoin on rats that are given lung defect using hyperoxia-reoxygenation

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that causes significant morbidity and mortality in premature infants. Inflammation and oxidative defect play an important role in BPD pathogenesis. Currently there is no treatment model proved to be effective in that area. In our study, we researched histopathological and biochemical effects of prophylactic Vitamin A and Isotretinoin on rats that are given lung defect using hyperoxia-reoxygenation. In our experiment, which started on the third day of postnatal period and ended on the 13th day, neonatal baby rats were classified randomly into four groups: Group 1 (Room air + Control, n=12), Group 2 (Serum Physiologic + Hyperoxia, n=12), Group 3 (Vitamin A + Hyperoxia, n=12), and Group 4 (Isotretinoin + Hyperoxia, n=12). Group 1 and 2 were given intraperitoneal serum physiologic; Group 3 was given 5000 IU/day Vitamin A with intraperitoneal insulin injector for 3 days per week; and Group 4 was given daily 1 mcg/gr Isotretinoin that was put in soya oil using gastric lavage. In order to observe the effects of Vitamin A and Isotretinoin: alveolar surface area, fibrosis and smooth muscle actin (SMA) score were evaluated for their histopatologic effects on lung tissue; fattening, hydropic degeneration, apoptotic cells and fibrosis in liver were evaluated for their histopatologic effects on liver tissue; and IL-1β, IL-6, IL-10, IL-8 and TNF-α levels were evaluated for their effects on biochemical parameters. Findings of our study shows no statistically meaningful difference found between Vitamin A + Hyperoxia group and Isotretinoin + Hyperoxia group in terms of fibrosis in lungs (p>0.05). Alveolar surface area was apparently normal in the control group (p<0,001). Reduction in alveolar surface area was more apparent in SP + Hyperoxia group compared to other groups (p<0.001). Level of increase in lung surface area was statistically meaningful in Isotretinoin + Hyperoxia group compared to Vitamin A + Hyperoxia group (p<0.001). There was no meaningful difference between Vitamin A + Hyperoxia group and Isotretinoin + Hyperoxia group in terms of lung fibrosis (p>0.05). There was a statistically meaningful decrease in the number of SMA-painted cells in Vitamin A + Hyperoxia group and Isotretinoin Hyperoxia group compared to SP + Hyperoxia group (p<0.01). While there was no effect of Vitamin A or Isotretinoin on proinflammatory cytokines; level of anti-inflammatory IL-10 was statistically higher in Vitamin A + Hyperoxia group and Isotretinoin + Hyperoxia group compared to SP + Hyperoxia group (p<0.001). Histopathologically, no adverse effect caused by Vitamin A or Isotretinoin was found in liver tissue. In conclusion, we observed that Vitamin A and Isotretinoin therapy was superior to placebo therapy in our hyperoxic lung defect model in rats; there was no pathologic finding in liver tissues after using Vitamin A and RA; Isotretinoin increases anti-inflammatory IL-10 (an anti-inflammatory) level; and Isotretinoin usage may be considered safe based on data. Anahtar Kelimeler: Bronkopulmoner displazi, İzotretinoin, Vitamin A