The therapeutic effect and mechanism of niacin on acute lung injury in a rat model of hemorrhagic shock: Down-regulation of the reactive oxygen species–dependent …

KY Jeong, GJ Suh, WY Kwon, KS Kim… - Journal of Trauma …, 2015 - journals.lww.com
KY Jeong, GJ Suh, WY Kwon, KS Kim, YS Jung, YC Kye
Journal of Trauma and Acute Care Surgery, 2015journals.lww.com
BACKGROUND The purpose of the current study was to investigate the protective effect of
niacin on acute lung injury by the down-regulation of the nuclear factor κB (NF-κB) pathway
in hemorrhagic shock (HS) rats. METHODS HS was induced in male Sprague-Dawley rats
by withdrawing blood to maintain a mean arterial pressure of 20 mm Hg to 25 mm Hg for 40
minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS),
a low-dose of niacin (360 mg/kg, HS+ LD-NA), or a high dose of niacin (1,080 mg/kg, HS+ …
Abstract
BACKGROUND
The purpose of the current study was to investigate the protective effect of niacin on acute lung injury by the down-regulation of the nuclear factor κB (NF-κB) pathway in hemorrhagic shock (HS) rats.
METHODS
HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20 mm Hg to 25 mm Hg for 40 minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS+ LD-NA), or a high dose of niacin (1,080 mg/kg, HS+ HD-NA) were administered orally. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours after HS induction. We measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, MEK partner 1 activity, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We also measured TNF-α, IL-6, and IL-8 levels in the serum.
RESULTS
The survival rates of the sham, HS, HS+ LD-NA, and HS+ HD-NA groups were 6 of 6 (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate levels, and glutathione–glutathione disulfide ratios; decreased lung malondialdehyde levels; down-regulated the NF-κB pathway; suppressed TNF-α, IL-6, and IL-8 levels in the lung tissue and serum; and attenuated histologic lung damage.
CONCLUSION
A high dose of niacin attenuated lung inflammation, suppressed proinflammatory cytokine release, reduced histologic lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the down-regulation of the reactive oxygen species–dependent NF-κB pathway.
Lippincott Williams & Wilkins