Cytoprotective Effects of Nicotinamide Derivatives in Endothelial Cells

Słomińska, Ewa M.; Yuen, Ada H. Y.; Osman, Lana; Gębicki, Jerzy; Yacoub, M; Smolenski, Ryszard T.

doi:10.1080/15257770802146528

Cited by 18 publications

(10 citation statements)

References 9 publications

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“…For example, nicotinamide can protect the function of the blood brain barrier [156,157], influence arteriolar dilatation and blood flow [172], increase skin vascular permeability [173], potentially lead to decreased atherosclerotic plaque through inhibition of poly(ADP-ribose) polymerase [174], and promote platelet production through megakaryocyte maturation [175]. Nicotinamide also can maintain EC viability during ROS exposure [132,133,134,135,176]. Nicotinamide is believed to be responsible for the preservation of cerebral [177] and endocardial [178,179] ECs during models of oxidative stress [178,179].…”

Section: Nicotinamide Oxidative Stress and Cellular Survivalmentioning

confidence: 99%

The Vitamin Nicotinamide: Translating Nutrition into Clinical Care

et al. 2009

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Nicotinamide, the amide form of vitamin B3 (niacin), is changed to its mononucleotide compound with the enzyme nicotinic acide/nicotinamide adenylyl-transferase, and participates in the cellular energy metabolism that directly impacts normal physiology. However, nicotinamide also influences oxidative stress and modulates multiple pathways tied to both cellular survival and death. During disorders that include immune system dysfunction, diabetes, and aging-related diseases, nicotinamide is a robust cytoprotectant that blocks cellular inflammatory cell activation, early apoptotic phosphatidylserine exposure, and late nuclear DNA degradation. Nicotinamide relies upon unique cellular pathways that involve forkhead transcription factors, sirtuins, protein kinase B (Akt), Bad, caspases, and poly (ADP-ribose) polymerase that may offer a fine line with determining cellular longevity, cell survival, and unwanted cancer progression. If one is cognizant of the these considerations, it becomes evident that nicotinamide holds great potential for multiple disease entities, but the development of new therapeutic strategies rests heavily upon the elucidation of the novel cellular pathways that nicotinamide closely governs.

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Section: Nicotinamide Oxidative Stress and Cellular Survivalmentioning

confidence: 99%

The Vitamin Nicotinamide: Translating Nutrition into Clinical Care

et al. 2009

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“…Nicotinamide can protect the function of the blood‐brain barrier, 270 , 271 influence arteriolar dilatation and blood flow, 285 increase skin vascular permeability, 286 inhibit atherosclerotic plaque formation through inhibition of poly(ADP‐ribose) polymerase, 287 and foster platelet production through megakaryocyte maturation 288 . Nicotinamide can enhance endothelial cell viability during ROS exposure 181 , 250 , 261 , 289 . Nicotinamide also may reverse a previously sustained early apoptotic injury, 61 , 181 , 250 , 252 , 253 , 261 suggesting that apoptosis prior to reaching genomic DNA degradation is dynamic and reversible in nature 61 , 181 , 251 , 261 .…”

Section: Novel Cellular Pathways and Diabetesmentioning

confidence: 99%

“…288 Nicotinamide can enhance endothelial cell viability during ROS exposure. 181,250,261,289 Nicotinamide also may reverse a previously sustained early apoptotic injury, 61,181,250,252,253,261 suggesting that apoptosis prior to reaching genomic DNA degradation is dynamic and reversible in nature. 61,181,251,261 Yet some studies in mice suggest that nicotinamide may either prevent or contribute to atherosclerotic plaques over a 3-to 6-month progression.…”

Section: Nicotinamidementioning

confidence: 99%

Novel Avenues of Drug Discovery and Biomarkers for Diabetes Mellitus

Maiese

Chong

Shang

et al. 2011

The Journal of Clinical Pharmacology

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Globally, developed nations spend a significant amount of their resources on healthcare initiatives that poorly translate into increased population life expectancy. As an example, the United States devotes sixteen percent of its gross domestic product to healthcare, the highest level in the world, but falls behind other nations that enjoy greater individual life expectancy. These observations point to the need for pioneering avenues of drug discovery to increase lifespan with controlled costs. In particular, innovative drug development for metabolic disorders such as diabetes mellitus (DM) becomes increasingly critical given that the number of diabetic individuals will increase exponentially over the next twenty years. Here we discuss the elucidation and targeting of novel cellular pathways that are intimately tied to oxidative stress in DM for new treatment strategies. Pathways that involve wingless, NAD + precursors, and cytokines govern complex biological pathways that determine both cell survival and longevity during DM and its complications. Furthermore, the role of these entities as biomarkers for disease can further enhance their utility irrespective of their treatment potential. Greater understanding of the intricacies of these unique cellular mechanisms will shape future drug discovery for DM to provide focused clinical care with limited or absent long-term complications. Keywords biomarkers; diabetes; oxidative stress Healthcare and metabolic diseaseCompared with other nations throughout the world, the United States devotes 16% of the gross domestic product to healthcare and spending for each individual equal to $7,290, the highest levels in the world 1 . Total spending on pharmaceuticals is also the highest in the world with $878 per individual. Yet, life expectancy in years in the United States equals 78.1 years and trails behind other countries such as Japan that allots 8% of the gross domestic product on healthcare, spends $2,514 for each individual, and has a life expectancy of 82.6 years. Furthermore, the United States is ranked as having the highest level of obesity in the population at 34.3% while countries such as Japan have a 3.4% level of obesity 1 . These statistics are the results of multiple factors, but also can support the arguments for not only improved preventive health measures, but also new directions to treat multiple disorders that can lead to improved lifespan while minimizing economic burden.In particular, one can consider diabetes mellitus (DM), a metabolic disorder closely associated with increased weight gain 2,3 . DM reaches approximately 20 million individuals in the United States and more than 165 million individuals worldwide 4 . By 2030, DM may affect more than 360 million individuals. Additionally, a significant portion of the population has undiagnosed diabetes, illustrating the need for improved early diagnosis 5 . The incidence of impaired glucose tolerance in the young also raises further concerns 6 . Individuals with impaired glucose tolerance have a greate...

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“…For the biological and pharmacological properties of pyridine-3-carboxamide derivatives, see: Balzarini et al (2009); Baumbach et al (1995); Girgis et al (2006); Guzel & Salman (2009); Kuramochi et al (2005); Moë ll et al (2009); Slominska et al (2008); Ur et al (2004); Vigorita et al (1992). For bondlength data, see: Allen et al (1987).…”

Section: Related Literaturementioning

confidence: 99%

N-[5-Methyl-2-(2-nitrophenyl)-4-oxo-1,3-thiazolidin-3-yl]pyridine-3-carboxamide monohydrate

et al. 2011

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In the title compound, C16H14N4O4S·H2O, the benzene and pyridine rings make a dihedral angle of 85.8 (1)°. Both enantiomers of the chiral title compound are statistically disordered over the same position in the unit cell. The methyl and carbonyl group attached to the stereogenic center (C5 of the thiazolidine ring) were therefore refined with common site-occupation factors of 0.531 (9) and 0.469 (9), respectively, for each stereoisomer. In the crystal, intermolecular N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds link the molecules, forming a three-dimensional supramolecular network. The crystal structure further shows π–π stacking interactions [centroid–centroid distance = 3.5063 (13) Å] between the pyridine rings.

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Cytoprotective Effects of Nicotinamide Derivatives in Endothelial Cells

Cited by 18 publications

References 9 publications

The Vitamin Nicotinamide: Translating Nutrition into Clinical Care

The Vitamin Nicotinamide: Translating Nutrition into Clinical Care

Novel Avenues of Drug Discovery and Biomarkers for Diabetes Mellitus

N-[5-Methyl-2-(2-nitrophenyl)-4-oxo-1,3-thiazolidin-3-yl]pyridine-3-carboxamide monohydrate

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