Synergy of Antioxidants and Omega-3 Polyunsaturated Fatty Acids for Reducing Oxidative Stress and Inflammation in the Neonatal Rat Terminal Ileum.

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ESPR183
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Synergy of Antioxidants and Omega-3 Polyunsaturated Fatty Acids for Reducing Oxidative Stress and Inflammation in the Neonatal Rat Terminal Ileum. 

Mustafa G, Cai CL, Aranda JV, Beharry KD.  Departments of Pediatrics & Ophthalmology State University of New York Medical Center, Brooklyn, NY.  

Background. Extremely premature infants are at increased risk for oxygen radical diseases of the newborn, including necrotizing enterocolitis (NEC). Almost all extremely preterm infants experience intermittent hypoxia (IH) events and subsequent oxidative stress due to immature antioxidant systems. 

Objectives. We tested the hypothesis that early supplementation with antioxidants and/or omega 3 polyunsaturated fatty acids (n-3 PUFAs) protects the immature terminal ileum from inflammation and oxidative injury induced by neonatal IH.

Methods. Newborn rats were exposed to brief IH episodes (12%) during hyperoxia (50% O2) from the first day of life (P0) until P14 during which they received daily oral supplementation with: 1) omega-3 polyunsaturated fatty acids (n-3 PUFAs) in fish oil; 2) coenzyme Q10 (CoQ10) in olive oil (OO); 3) glutathione nanoparticles (nGSH); 4) n-3 PUFAs+CoQ10; or 5) OO (placebo controls). Pups were placed in RA from P14 to P21 with no further treatment. Control littermates remained in RA from birth to P21 with all treatments identical and served as RA controls. Terminal ileum was assessed at P21 for histopathology, oxidative stress (8-isoPGF), nitric oxide (NO) stable metabolites (NOx), marker for nitrosative stress), and biomarkers of inflammation.  

Results.  Histopathology showed severely shortened, damaged and denuded villi in the groups exposed to IH, characteristics that are consistent with NEC, that persisted despite recover/reoxygenation in RA. This was associated with higher 8-isoPGF, inducible cyclooxygenase and NO isoforms, and toll-like receptor-4. The most effective treatment for reducing oxidative stress, suppression inflammatory biomarkers, and preserving the terminal ileum integrity during neonatal IH were nGSH and combination CoQ10+PUFAs

Conclusions.  Early postnatal supplementation with antioxidants and/or n-3 PUFAs during neonatal IH may be favorable for preserving gut integrity and reducing oxidative injury. These beneficial effects appear to be associated with elevations in vasodilators and reductions in vasoconstrictors, oxidative stress, and inflammation.

 
SUNY Downstate Medical Center
SUNY Downstate Medical Centre

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