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Abstract
Aims
Sepsis-caused multiple organ failure remains the major cause of morbidity and
mortality in intensive care units. Nicotinamide riboside (NR) is a precursor of
nicotinamide adenine dinucleotide (NAD+), which is important in regulating oxidative
stress. This study investigated whether administration of NR prevented oxidative
stress and organ injury in sepsis.
Methods
Mouse sepsis models were induced by injection of lipopolysaccharides (LPS) or
feces-injection-in-peritoneum. NR was given before sepsis onset. Cultured
macrophages and endothelial cells were incubated with various agents.
Results
Administration of NR elevated the NAD+ levels, and elicited a reduction of oxidative
stress, inflammation and caspase-3 activity in lung and heart tissues, which correlated
with attenuation of pulmonary microvascular permeability and myocardial
dysfunction, leading to less mortality in sepsis models. These protective effects of NR
were associated with decreased levels of plasma high mobility group box-1 (HMGB1)
in septic mice. Consistently, pre-treatment of macrophages with NR increased NAD
content and reduced HMGB1 release upon LPS stimulation. NR also prevented
reactive oxygen species (ROS) production and apoptosis in endothelial cells induced
by a conditioned-medium collected from LPS-treated macrophages. Furthermore,
inhibition of SIRT1 by EX527 offset the negative effects of NR on HMGB1 release in
macrophages, and ROS and apoptosis in endothelial cells.
Conclusions
Administration of NR prevents lung and heart injury, and improves the survival in
sepsis, likely by inhibiting HMGB1 release and oxidative stress via the NAD
/SIRT1 signaling. Given NR has been used as a health supplement, it may be a useful agent to
prevent organ injury in sepsis.
Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis
Guangliang Hong, Dong Zheng, Zhang Lulu, Rui
Ni, Grace Wang, Guo-Chang Fan, Zhongqiu Lu,
Tianqing Peng
PII: S0891-5849(18)30906-7
DOI: https://doi.org/10.1...med.2018.05.073
Reference: FRB13775
To appear in:
Free Radical Biology and Medicine
