Next Article in Journal
Association of Serum Bilirubin with the Severity and Outcomes of Intracerebral Hemorrhages
Next Article in Special Issue
Male Disadvantage in Oxidative Stress-Associated Complications of Prematurity: A Systematic Review, Meta-Analysis and Meta-Regression
Previous Article in Journal
High-Carbohydrate Diet Alleviates the Oxidative Stress, Inflammation and Apoptosis of Megalobrama amblycephala Following Dietary Exposure to Silver Nanoparticles
Previous Article in Special Issue
NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats
Article

NAC and Vitamin D Improve CNS and Plasma Oxidative Stress in Neonatal HIE and Are Associated with Favorable Long-Term Outcomes

1
Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, 10 McClennan Banks Drive, Charleston, SC 29425, USA
2
Center for Biomedical Imaging, Department of Radiology, Medical University of South Carolina, Charleston, SC 29425, USA
3
Centre for Perinatal Neuroscience, Imperial College London, London W12 0HS, UK
4
Neonatal Research Group, Health Research Institute Hospital La Fe, 46026 Valencia, Spain
5
Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC 29425, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Gaspar Ros Berruezo and Stanley Omaye
Antioxidants 2021, 10(9), 1344; https://doi.org/10.3390/antiox10091344
Received: 21 July 2021 / Revised: 11 August 2021 / Accepted: 23 August 2021 / Published: 25 August 2021
N-acetylcysteine (NAC) and vitamin D provide effective neuroprotection in animal models of severe or inflammation-sensitized hypoxic ischemic encephalopathy (HIE). To translate these FDA-approved drugs to HIE neonates, we conducted an early phase, open-label trial of 10 days of NAC (25, 40 mg/kg q12h) + 1,25(OH)2D (calcitriol 0.05 mg/kg q12h, 0.03 mg/kg q24h), (NVD), for pharmacokinetic (PK) estimates during therapeutic hypothermia and normothermia. We paired PK samples with pharmacodynamic (PD) targets of plasma isoprostanoids, CNS glutathione (GSH) and total creatine (tCr) by serial MRS in basal ganglia (BG) before and after NVD infusion at five days. Infants had moderate (n = 14) or severe HIE (n = 16), funisitis (32%), and vitamin D deficiency (75%). NVD resulted in rapid, dose-responsive increases in CNS GSH and tCr that correlated positively with plasma [NAC], inversely with plasma isofurans, and was greater in infants with lower baseline [GSH] and [tCr], suggesting increases in these PD markers were titrated by neural demand. Hypothermia and normothermia altered NAC PK estimates. NVD was well tolerated. Excluding genetic syndromes (2), prolonged ECMO (2), lost-to-follow-up (1) and SIDS death (1), 24 NVD treated HIE infants have no evidence of cerebral palsy, autism or cognitive delay at 24–48 months. These data confirm that low, safe doses of NVD in HIE neonates decreased oxidative stress in plasma and CNS, improved CNS energetics, and are associated with favorable developmental outcomes at two to four years. View Full-Text
Keywords: N-acetylcysteine; vitamin D; neonatal HIE; oxidative stress; MRS N-acetylcysteine; vitamin D; neonatal HIE; oxidative stress; MRS
Show Figures

Graphical abstract

MDPI and ACS Style

Jenkins, D.D.; Moss, H.G.; Brown, T.R.; Yazdani, M.; Thayyil, S.; Montaldo, P.; Vento, M.; Kuligowski, J.; Wagner, C.; Hollis, B.W.; Wiest, D.B. NAC and Vitamin D Improve CNS and Plasma Oxidative Stress in Neonatal HIE and Are Associated with Favorable Long-Term Outcomes. Antioxidants 2021, 10, 1344. https://doi.org/10.3390/antiox10091344

AMA Style

Jenkins DD, Moss HG, Brown TR, Yazdani M, Thayyil S, Montaldo P, Vento M, Kuligowski J, Wagner C, Hollis BW, Wiest DB. NAC and Vitamin D Improve CNS and Plasma Oxidative Stress in Neonatal HIE and Are Associated with Favorable Long-Term Outcomes. Antioxidants. 2021; 10(9):1344. https://doi.org/10.3390/antiox10091344

Chicago/Turabian Style

Jenkins, Dorothea D., Hunter G. Moss, Truman R. Brown, Milad Yazdani, Sudhin Thayyil, Paolo Montaldo, Maximo Vento, Julia Kuligowski, Carol Wagner, Bruce W. Hollis, and Donald B. Wiest 2021. "NAC and Vitamin D Improve CNS and Plasma Oxidative Stress in Neonatal HIE and Are Associated with Favorable Long-Term Outcomes" Antioxidants 10, no. 9: 1344. https://doi.org/10.3390/antiox10091344

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop