• Woon Yong Kwon, Gil Joon Suh, Kyung Su Kim, Yoon Sun Jung, Sung Hee Kim, A Rum Lee, Kyoung Min You, and Min Ji Park.
• Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
• Crit. Care Med. 2018 Aug 1; 46 (8): e788-e796.

ObjectivesTo determine neuroprotective effects and mechanism of the combination therapy of niacin and selenium in cardiac arrest rats.DesignProspective laboratory study.SettingUniversity laboratory.SubjectsRat cortex neurons and male Sprague-Dawley rats (n = 68).InterventionsIn 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 ResultsIn 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).ConclusionsThe 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.

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