Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-κB pathway.
OBJECTIVE
To examine whether niacin attenuates lung inflammation and improves survival during sepsis and to determine whether the beneficial effects of niacin are associated with downregulation of the nuclear factor (NF)-κB pathway.


METHODS
Prospective laboratory study.


METHODS
University laboratory.


METHODS
Male Sprague-Dawley rats (n = 119).


METHODS
To induce endotoxemia in rats, lipopolysaccharide (Escherichia coli, O26:B6) at a dosage of 10 mg/kg was injected into a tail vein and 10 mins later, vehicle, a low dose of niacin (360 mg/kg), or a high dose of niacin (1180 mg/kg) was administered once through an orogastric tube, respectively.


RESULTS
We observed the survival of the subjects for 72 hrs. At 6 hrs postlipopolysaccharide, we euthanized animals and measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, tumor necrosis factor-α, and interleukin-6 gene expressions and histologic damages in lung tissues. We also measured nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, and malondialdehyde levels in lung tissues. High dose of niacin suppressed NF-κB activation and proinflammatory cytokine gene expressions in lung tissues, reduced histologic lung damages, and improved survival in endotoxemic rats. Furthermore, it increased nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and glutathione levels and decreased malondialdehyde level in lung tissues.


CONCLUSIONS
High dose of niacin attenuated lung inflammation, reduced histologic lung damages, and improved survival during sepsis in rats. These therapeutic benefits were associated with downregulation of the NF-κB pathway.
Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea.
Woon Yong
WY
Kwon
Gil Joon
GJ
Suh
Kyung Su
KS
Kim
Young Ho
YH
Kwak
D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D015536:Down-Regulation; D019446:Endotoxemia / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics; D009525:Niacin / Q000008:administration & dosage*; D011014:Pneumonia / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D020551:Pulse Therapy, Drug; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015996:Survival Rate; D013997:Time Factors
D016328:NF-kappa B; D009525:Niacin