Comparison of coenzyme Q10 or fish oil for prevention of intermittent hypoxia-induced oxidative injury in neonatal rat lungs

Abstract

Background Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats. Methods Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O2 with brief hypoxia (12% O2); or (2) room air (RA) with brief hypoxia (12% O2), until P14 during which they were supplemented with daily oral CoQ10, fish oil, or olive oil from P0 to P14. Pups were studied at P14 or placed in RA until P21 with no further treatment. Lungs were assessed for histopathology and morphometry; biomarkers of oxidative stress and lipid peroxidation; and antioxidants. Results Of the two neonatal IH paradigms 21%/12% O2 IH resulted in the most severe outcomes, evidenced by histopathology and morphometry. CoQ10 was effective for preserving lung architecture and reduction of IH-induced oxidative stress biomarkers. In contrast, fish oil resulted in significant adverse outcomes including oversimplified alveoli, hemorrhage, reduced secondary crest formation and thickened septae. This was associated with elevated oxidants and antioxidants activities. Conclusions Data suggest that higher FiO2 may be needed between IH episodes to curtail the damaging effects of IH, and to provide the lungs with necessary respite. The negative outcomes with fish oil supplementation suggest oxidative stress-induced lipid peroxidation.

Biomarkers of lung alveolarization and microvascular maturation in response to intermittent hypoxia and/or early antioxidant/fish oil supplementation in neonatal rats

“…The IH profile consisted of an initial exposure of hyperoxia (50% O 2 ) for 30 min followed by three brief, 1‐min, clustered hypoxic events (12% O 2 ), with a 10‐min reoxygenation in 50% O 2 between each hypoxic event. Recovery between each IH episode occurred in 50% O 2 following each clustered IH event for 2.5 h for a total of eight clustering IH episodes per day for 14 days, as previously described 24–26 . This clustering IH pattern was first reported in newborn rats by Coleman et al 30 Studies in preterm infants confirm that early patterns of IH put infants at risk for future development of severe ROP 31 …”

“…Images were captured at ×20 magnification using an Olympus BX53 microscope, DP72 digital camera, and CellSens imaging software (Olympus), attached to a Dell Precision T3500 computer (Dell). Morphometric analyses included total alveolar space (μM 2 ); number of secondary crests; and width of the alveolar septae (μM), as previously described 24,25 . To assess alveolarization, two methods were used: (1) the radial alveolar count (RAC); and (2) the mean linear intercept (MLI).…”

“…At P0, RA, and IH exposed pups were randomized to receive 50 µL oral supplementation of: (1) extra virgin olive oil (OO); (2) coenzyme Q10 (CoQ10) in OO; (3) oral fish oil; (4) glutathione nanoparticle sublingual drops (nGSH, 200 mg/mL, optimized for instant absorption) diluted to 24 µg in 50 µL with extra virgin OO; or (5) combination CoQ10 + fish oil from the 1st day of life (P0) to P14. The doses of CoQ10 and fish oil, and methods of daily supplementation, were based on previous findings 25,26 . CoQ10 is lipid soluble.…”

“…Morphometric analyses included total alveolar space (μM 2 ); number of secondary crests; and width of the alveolar septae (μM), as previously described. 24,25 To assess alveolarization, two methods were used:…”

“…The doses of CoQ10 and fish oil, and methods of daily supplementation, were based on previous findings. 25,26 CoQ10 is lipid soluble. The choice for extra virgin oil was based on previous reports.…”