Oxidative stress in critically ill ventilated adults: effects of vitamin D-3 and associations with alveolar macrophage function

• Type of Material: Article
• Authors: Jenny Elizabeth Han, Emory University; Jessica A. Alvarez, Emory University; Bashar S. Staitieh, Emory University; Vin Tangpricha, Emory University; Li Hao, Emory University; Thomas R Ziegler, Emory University; Greg Martin, Emory University; Lou Ann Brown, Emory University
• Language: English
• Date: 2018-05-01
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Macmillan Publishers Limited, part of Springer Nature.
• Final Published Version (URL): http://dx.doi.org/10.1038/s41430-017-0047-0
• Title of Journal or Parent Work: European Journal of Clinical Nutrition
• ISSN: 0954-3007
• Volume: 72
• Issue: 5
• Start Page: 744
• End Page: 751
• Grant/Funding Information: This project was supported, in part, by National Institutes of Health grants: NIH R21 HL110044 (GSM, TRZ, LAB, VT, JEH), K24 DK096574 (TRZ), UL1 TR000454 (JEH, GSM, TRZ, VT), K01 DK102851 (JAA), T32 HL076118 (BS), and T32 AA013528 (JEH).
• Keywords: MARKERS; REDOX STATUS; GUANYLATE-CYCLASE; RANDOMIZED CONTROLLED-TRIAL; RESPIRATORY-DISTRESS-SYNDROME; FLUID; NITRIC-OXIDE; PROFILE; GLUTATHIONE; Science & Technology; Life Sciences & Biomedicine; Nutrition & Dietetics; D DEFICIENCY

Abstract

Background/objectives: Disruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: (1) characterize the plasma and alveolar thiol/disulfide redox pools, (2) examine their associations with alveolar macrophage phagocytosis, and (3) determine the effect of high dose Vitamin D3on plasma thiol/disulfide redox. Subjects/methods: Subjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) Vitamin D3or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14. Results: Baseline plasma Cys was inversely associated with alveolar PI (ρ = -0.69, P = 0.003), and EhCySS was positively associated with PI (ρ = 0.61, P = 0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in EhGSSG (P < 0.01 for both), with no difference by treatment group. Vitamin D3decreased oxidized plasma GSSG to a more normal state (P for group x time = 0.009). Conclusions: Oxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose Vitamin D3decreased plasma GSSG concentrations, which suggests that Vitamin D can possibly improve the oxidative stress environment.