Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats.

Kay Beharry,Sara Chowdhury,Jacob Aranda,Michael Henry,Charles Cai,Gloria Valencia

doi:10.3390/antiox6040103

Kay Beharry, Sara Chowdhury + Show 4 more

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https://doi.org/10.3390/antiox6040103

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Abstract

Neonatal intermittent hypoxia (IH) increases the risk for many morbidities in extremely low birth weight/gestational age (ELBW/ELGA) neonates with compromised antioxidant systems and poor growth. We hypothesized that supplementation with coenzyme Q10 (CoQ10, ubiquinol) or n-3 polyunsaturated fatty acids (PUFAs) during neonatal IH improves antioxidant profiles and somatic growth in neonatal rats. Newborn rats were exposed to two IH paradigms at birth (P0): (1) 50% O2 with brief hypoxic episodes (12% O2); or (2) room air (RA) with brief hypoxia, until P14 during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only from P0 to P14. Pups were studied at P14 or placed in RA until P21 for recovery from IH (IHR). Body weight and length; organ weights; and serum antioxidants and growth factors were determined at P14 and P21. Neonatal IH resulted in sustained reductions in somatic growth, an effect that was reversed with n-3 PUFAs. Improved growth was associated with higher serum growth factors. CoQ10 decreased superoxide dismutase (SOD) and glutathione, but increased catalase, suggesting reduced oxidative stress. Further studies are needed to determine the synergistic effects of CoQ10 and n-3 PUFA co-administration for the prevention of IH-induced oxidative stress and postnatal growth deficits.

Highlights

Neonatal intermittent hypoxia (IH), defined as brief, repetitive cycles of arterial oxygen desaturations followed by re-oxygenation, often occurs in extremely low birth weight (ELBW)/extremely low gestational age (ELGA) neonates requiring oxygen supplementation and/or mechanical ventilation [1]
IH-induced growth following restrictionan byIHimproving antioxidant profiles are andclinically altering with to reverses re-oxygenation in hyperoxia event as these two paradigms relevant. These studies provided several interesting and important findings regarding growth: (1) Re-oxygenation in room air (RA) following an IH event causes sustained deficits in body weight and length accretion comparable with re-oxygenation in hyperoxia following an IH event, with no evidence of catchup growth during the recovery, IHR period. This finding was surprising considering the shorter range of oxygen variation from 21% O2 to 12% O2 versus 50% O2 to 12% O2, and implicates IH, but not hyperoxia, in the sustained suppression of somatic growth; (2) Supplementation with Coenzyme Q10 (CoQ10) did not reverse IH-induced growth restriction in the 50–12% O2 group, and moderately improved growth accretion in the 21–12% O2 group, but was effective for improving body length accretion in both IH groups; (3) Supplementation with n-3 polyunsaturated fatty acids (PUFAs) facilitated the most beneficial effects with significant improvements in body weight and length during and post treatment in IH, resulting in taller pups compared to their IH counterparts
It was interesting to note that in addition to overall body growth benefits, n-3 PUFA supplementation induced brain, liver and kidney mass and size suggesting that both CoQ10 and n-3 PUFAs may target these organs with significant weight sparing in the case of n-3 PUFAs, the liver when exposed to chronic neonatal IH

Summary

Introduction

Neonatal intermittent hypoxia (IH), defined as brief, repetitive cycles of arterial oxygen desaturations followed by re-oxygenation, often occurs in extremely low birth weight (ELBW)/extremely low gestational age (ELGA) neonates requiring oxygen supplementation and/or mechanical ventilation [1]. Re-oxygenation following an IH event (IHR) can occur in normoxia or hyperoxia, but whether the effects of IH with resolution in normoxia are less deleterious than that in hyperoxia, remains to be determined. After numerous episodes, occurring within minutes of each other, a “critical” point is achieved where the mechanisms induced by IH become indistinguishable from those induced by IHR [6]. The merging of these mechanisms has profound deleterious effects on mitochondrial homeostasis and redox state [7]

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