253 - Effect of Phthalate Exposure on Development of Bronchopulmonary Dysplasia in a Newborn Rat Model

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease among children. BPD is a complex and multifactorial condition with unclear etiology. Various factors including exposure to oxygen, infection, inflammation, and toxins have been implicated in the development of this devastating condition among premature infants. Phthalates are a family of chemicals used to improve the flexibility and durability of a variety of types of plastic medical equipment. Preterm infants requiring intensive care are exposed to high levels of phthalates via medical tubing and devices. These exposures may contribute to the development of Bronchopulmonary dysplasia.

Objective: Di (2-ethylhexyl) phthalate (DEHP) exposure in early neonatal period is associated with enhanced oxidative injury in the immature rat lung leading to changes consistent with bronchopulmonary dysplasia

Design/Methods: Newborn rat pups were divided into 4 exposure groups: control (room air), hyperoxia (60% oxygen), hyperoxia + DEHP (60% oxygen and 25mg/m3 DEHP for 6 hours per day), and DEHP (25mg/m3 for 6 hours per day). Each group was maintained in the group environment from birth to 14 days of life. Urine samples were collected weekly for future phthalate measurement. All pups were sacrificed on 14^th day and lung tissue and blood were collected for histopathology and to measure markers of inflammation and angiogenesis. Endothelin 1(ET-1) was measured via ELISA in serum. VEGF, SFlt-1, KDR/Flk-1 and eNOS were measured in lung homogenates by RT-qPCR and Western blot. Histopathological studies were performed using H&E staining

Results:

The hyperoxia + DEHP group showed scanty blood vessels, distorted alveolar growth, and increased septal wall thickness (P < 0.001) as histopathological evidence of poor angiogenesis and alveologenesis compared to both the hyperoxia alone and control groups. The hyperoxia + DEHP group also showed a significant decrease in expression of the pro-angiogenic factors VEGF, VEGFR2 (KDR/Flk-1), and eNOS as well as enhanced expression of the anti-angiogenic factor SFlt1 compared to the DEHP only or hyperoxia only groups (P< 0.05). The hyperoxia + DEHP group also showed enhanced expression of ET-1 (a potent inflammatory marker) compared to controls (P< 0.001).

 

Conclusion(s):

Our results indicate that DEHP exposure in early life produces an exaggerated histopathologic finding consistent with the development of BPD and an anti-angiogenic state in the neonatal rat lung. These findings support our hypothesis and may provide a promising target for a modifiable contributor to the development of BPD for future exploration.  

 
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