The effects of subcutaneous breast milk exosome on hyperoxia-induced lung injury in neonatal rats

Bronchopulmonary dysplasia (BPD), which is one of the most important causes of morbidity and mortality affecting premature infants, has no proven treatment or preventive strategy. In this study, we planned to investigate the histopathologic and biochemical effects of subcutaneous breast milk exosome in the lungs of neonatal rats in which BPD was induced by hyperoxic lung injury (HLI). Sprague-Dawley rat pups in which HLI was induced were exposed to hyperoxia (oxygen concentration 85%) in a closed space made of plexiglass from postnatal day one to postnatal day seven. Oxygen concentration was checked twice a day (anesthetic gas monitor, Drager, 1996) and humidity was kept between 60-80%. Carbon dioxide was removed from the environment with soda-lime. Rat pups were divided into six groups of eight in each. Group I (room air, control group, n=8), Group II (HLI model, n=8), Group III (prophylaxis placebo group, HLI+1.-6. days subcutaneous saline administered, n=8), Group IV (prophylaxis treatment group, HLI+1.-6. days, subcutaneous breast milk exosome administered n=8), Group V (placebo treatment group, HLI+7.-11. days, subcutaneous saline administered, n=8), Group VI (treatment group, HLI+7.-11. days, subcutaneous breast milk exosome administered, n=8). Groups I, II, III and IV were euthanized on postnatal day 7, and groups V and VI on postnatal day 11. After euthanasia, alveolar surface area score, fibrosis and smooth muscle actin score were evaluated in the right lung tissue samples of the rats. Left lung tissue samples were analyzed for total antioxidant capacity (TAC) and total oxidant capacity (TOC) levels with commercial ELISA kits, and TAC and TOC levels in blood obtained by cardiac intervention with commercial ELISA kits were analyzed by antigen antibody reaction based sandwich immunoassay method in the Medical Biochemistry Research Laboratory. Both lung alveolar surface area score and smooth muscle actin score were significantly higher in the HLI model compared to the control group (p<0.05), but no difference was found in terms of fibrosis (p>0.05). TOC levels in both lung tissue and blood were found to be higher in the HLI group compared to the control group, but not statistically significant.Prophylactic administration of breast milk exosome significantly decreased both lung alveolar surface area score and smooth muscle actin score compared to groups II, III, V and VI (p<0.05) and no statistical difference was found between theprophylactic treatment groupand the control group. In addition, prophylactic breast milk exosome administration significantly decreased lung tissue TOS levels compared to both HLI group and placebo group (p<0.05). In conclusion, in this experimental study in which hyperoxic lung injury and BPD model were established, it was shown that prophylactic breast milk exosome administration has a preventive effect on lung injury both histopathologically and biochemically. In recent years, especially early diagnosis and preventive strategies have been emphasized. In this respect, we think that our study is important in terms of prophylactic administration of breast milk exosome as a preventive treatment method to infants with a high probability of developing BPD, but more comprehensive and further studies are needed in this field. Keywords: Breast milk exosome, hyperoxia-induced lung injury, treatment