Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis

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-inperitoneum. 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, in-flammation 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.

Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure

“…The reduction of systemic inflammation through inhibition of proinflammatory activation of circulating immune cells allows the system to break from the vicious cycle that perpetuates the disease. Mechanistically, NAD + repletion by NR has been shown to reduce mtROS production across tissue types (15,(43)(44)(45)(46), which suppresses NLRP3 inflammasome/caspase I axis and secretions of active IL-1B and IL-18 ( Figure 5 and ref. 28).…”

LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis

“…Sepsis-induced cardiomyopathy (SIC) is an infection-related cardiovascular disease. Studies have shown that at least 50% of patients with septic shock are clinically diagnosed with septic cardiomyopathy (Condor et al 2017 ; Hong et al 2018 ). Therefore, properly handling with the sepsis-induced heart failure became the urgent goal for all physicians worldwide.…”

Clinical Impact Potential of Supplemental Nutrients as Adjuncts of Therapy in High-Risk COVID-19 for Obese Patients

“…Because the increased activity of PARP elevates the inflammatory cytokines that contribute to the cytokine storm, vitamin B3 therapy may reduce cytokine storm in COVID-19 (6). The pyridine-nucleoside form of vitamin B3 called nicotinamide riboside functions as a precursor to nicotinamide adenine dinucleotide (NAD + ), prevented ALI/ARDS and heart injury, and improved the survival of mice after the LPS challenge or sepsis caused by intraperitoneal injection of feces (150). In LPSchallenged rats, the administration of nicotinamide prevented the decrease in mitochondrial respiration and intracellular NAD + levels in macrophages (151).…”