Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects

Podyacheva, Ekaterina; Toropova, Yana

doi:10.3390/nu13103435

Cited by 12 publications

(6 citation statements)

References 120 publications

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“…To better understand the role of NAD metabolism during pro-inflammatory macrophage activation, we investigated the effect of supplementation with different NAD + precursors on macrophage activation. The NAD + precursors NMN and NR have been extensively studied and supplementation with these NAD + intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiology and disease conditions (2,39,40). To determine whether NAD precursors regulate the inflammatory phenotype in macrophages, we performed our supplementation experiments in resting BMDM, comparing the effects of NMN, NR, and NAM with the recently described precursor NRH.…”

Section: Discussionmentioning

confidence: 99%

Dihydronicotinamide Riboside Is a Potent NAD+ Precursor Promoting a Pro-Inflammatory Phenotype in Macrophages

Chini

Peclat²,

Gomez³

et al. 2022

Front. Immunol.

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Nicotinamide adenine dinucleotide (NAD) metabolism plays an important role in the regulation of immune function. However, a complete picture of how NAD, its metabolites, precursors, and metabolizing enzymes work together in regulating immune function and inflammatory diseases is still not fully understood. Surprisingly, few studies have compared the effect of different forms of vitamin B3 on cellular functions. Therefore, we investigated the role of NAD boosting in the regulation of macrophage activation and function using different NAD precursors supplementation. We compared nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide (NAM) supplementation, with the recently described potent NAD precursor NRH. Our results show that only NRH supplementation strongly increased NAD+ levels in both bone marrow-derived and THP-1 macrophages. Importantly, NRH supplementation activated a pro-inflammatory phenotype in resting macrophages, inducing gene expression of several cytokines, chemokines, and enzymes. NRH also potentiated the effect of lipopolysaccharide (LPS) on macrophage activation and cytokine gene expression, suggesting that potent NAD+ precursors can promote inflammation in macrophages. The effect of NRH in NAD+ boosting and gene expression was blocked by inhibitors of adenosine kinase, equilibrative nucleoside transporters (ENT), and IκB kinase (IKK). Interestingly, the IKK inhibitor, BMS-345541, blocked the mRNA expression of several enzymes and transporters involved in the NAD boosting effect of NRH, indicating that IKK is also a regulator of NAD metabolism. In conclusion, NAD precursors such as NRH may be important tools to understand the role of NAD and NADH metabolism in the inflammatory process of other immune cells, and to reprogram immune cells to a pro-inflammatory phenotype, such as the M2 to M1 switch in macrophage reprogramming, in the cancer microenvironment.

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Section: Discussionmentioning

confidence: 99%

Dihydronicotinamide Riboside Is a Potent NAD+ Precursor Promoting a Pro-Inflammatory Phenotype in Macrophages

Chini

Peclat²,

Gomez³

et al. 2022

Front. Immunol.

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“…administered to assess its ability to mitigate doxorubicin (DOX)-induced cardiomyopathy. OXS, autolysosomes accumulation and autophagic flux blockade because of DOX cardiotoxicity were all prevented by NR via NAD + /SIRT1 signaling pathway [ 87 , 88 ]. For the specific pathogen-free male Wistar rats, the protective effect exhibited significant levels through the preventive use of NR [ 89 ].…”

Section: Effects Of Nicotinamide Riboside On Several Organs and Systemsmentioning

confidence: 99%

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives

Biță

Scorei²,

Ciocîlteu

et al. 2023

Molecules

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Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging and longevity appear to be closely related to NAD+ and its related metabolites, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). As a dietary supplement, NR appears to be well tolerated, having better pharmacodynamics and greater potency. Unfortunately, NR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Recently, work related to prebiotic chemistry discovered that NR borate is considerably more stable than NR itself. However, immediately upon consumption, the borate dissociates from the NR borate and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NR left behind is expected to behave pharmacologically in ways identical to NR itself. This review provides a comprehensive summary (through Q1 of 2023) of the literature that makes the case for the consumption of NR as a dietary supplement. It then summarizes the challenges of delivering quality NR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NR borate in these processes.

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“…Four pathways have been identified for the biosynthesis of NAD + (as shown in Figure 2): (1) the De novo pathway (also known as the kynurenine pathway), which involves eight steps and metabolizes tryptophan; (2) the Preiss-Handler pathway, which uses both exogenous and endogenous nicotinic acid (NA); (3) the Salvage pathway, which produces NAD + from nicotinamide riboside (NR); and (4) the Core Recycling pathway, which recycles NAD + from nicotinamide (NAM) [35]. In each of these pathways its own enzyme systems are uses.…”

Section: Nad + Metabolismmentioning

confidence: 99%

The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis

Podyacheva

Toropova

2023

IJMS

Self Cite

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The World Health Organization has identified oncological diseases as one of the most serious health concerns of the current century. Current research on oncogenesis is focused on the molecular mechanisms of energy-biochemical reprogramming in cancer cell metabolism, including processes contributing to the Warburg effect and the pro-oncogenic and anti-oncogenic roles of sirtuins (SIRTs) and poly-(ADP-ribose) polymerases (PARPs). However, a clear understanding of the interaction between NAD+, SIRTs in cancer development, as well as their effects on carcinogenesis, has not been established, and literature data vary greatly. This work aims to provide a summary and structure of the available information on NAD+, SIRTs interactions in both stimulating and countering carcinogenesis, and to discuss potential approaches for pharmacological modulation of these interactions to achieve an anticancer effect.

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Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects

Cited by 12 publications

References 120 publications

Dihydronicotinamide Riboside Is a Potent NAD+ Precursor Promoting a Pro-Inflammatory Phenotype in Macrophages

Dihydronicotinamide Riboside Is a Potent NAD+ Precursor Promoting a Pro-Inflammatory Phenotype in Macrophages

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for Healthy Aging and Longevity: Current Research and Perspectives

The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis

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