Niacin and Selenium Attenuate Brain Injury After Cardiac Arrest in Rats by Up-Regulating DJ-1-Akt Signaling

Objectives: To determine neuroprotective effects and mechanism of the combination therapy of niacin and selenium in cardiac arrest rats. Design: Prospective laboratory study. Setting: University laboratory. Subjects: Rat cortex neurons and male Sprague-Dawley rats (n = 68). Interventions: In rat cortex neurons underwent 90 minutes of oxygen-glucose deprivation and 22.5 hours of reoxygenation, effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 μM) were investigated. The role of DJ-1 was determined using DJ-1 knockdown cells. In cardiac arrest rats, posttreatment effects of the combination therapy of niacin (360 mg/kg) and selenium (60 μg/kg) were evaluated. Measurements and Main Results: In oxygen-glucose deprivation and 22.5 hours of reoxygenation cells, combination therapy synergistically activated the glutathione redox cycle by a niacin-induced increase in glutathione reductase and a selenium-induced increase in glutathione peroxidase activities and reduced hydrogen peroxide level. It increased phosphorylated Akt and intranuclear Nuclear factor erythroid 2–related factor 2 expression and attenuated neuronal injury. However, these benefits were negated by DJ-1 knockdown. In cardiac arrest rats, combination therapy increased DJ-1, phosphorylated Akt, and intranuclear nuclear factor erythroid 2–related factor 2 expression, suppressed caspase 3 cleavage, and attenuated histologic injury in the brain tissues. It also improved the 7-day Neurologic Deficit Scales from 71.5 (66.0–74.0) to 77.0 (74.–80.0) (p = 0.02). Conclusions: The combination therapy of clinically relevant doses of niacin and selenium attenuated brain injury and improved neurologic outcome in cardiac arrest rats. Its benefits were associated with reactive oxygen species reduction and subsequent DJ-1-Akt signaling up-regulation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare (grant number: HI12C1117). All authors have disclosed that this work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare (grant number: HI12C1117). For information regarding this article, E-mail: suhgil@snu.ac.kr Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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