Metabolic Effects and Liver Damage after Prolonged Administration of High Doses of Nicotinamide to Rats

Jaus, Heinrich; Sturm, G.; Grässle, B.; Romen, W; Siebert, Günther

doi:10.1159/000176101

Cited by 3 publications

(2 citation statements)

References 1 publication

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“…It should be noted that large doses of nicotinic acid and nicotinamide may induce liver damage [45,46] , therefore, long-term investigation may be necessary to determine the relationship between chronic nicotinamide overload and non-alcoholic steatohepatitis. Historically, the epidemic of pellagra has been restricted mainly to those who have performed heavy industrial labor with poor nutrient supply [9] .…”

Section: Aox Skin Aoxmentioning

confidence: 99%

Nicotinamide overload may play a role in the developmentof type 2 diabetes

Zhou

Li²,

Sun³

et al. 2009

WJG

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AIM:To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS:Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N 1 -methylnicotinamide on glucose metabolism, plasma H2O2 levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS:Diabetic subjects had significantly higher plasma N 1 -methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N 1 -methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N 1 -methylnicotinamide. Moreover, cumulative exposure to N 1 -methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N 1 -methylnicotinamide in vitro . Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N 1 -methylnicotinamide clearance. CONCLUSION:These findings suggest that nicotinamide overload, which induced an increase in plasma N 1 -methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

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Section: Aox Skin Aoxmentioning

confidence: 99%

Nicotinamide overload may play a role in the developmentof type 2 diabetes

Zhou

Li²,

Sun³

et al. 2009

WJG

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show abstract

“…This thesis is consistent with the fact that rapid-acting niacin, which is less prone to damage the liver, is more likely to be excreted as nicotinuric acid than is timerelease niacin. Also consistent is the fact that niacinamide, which lacks the hypolipidemic and flush-inducing effects of niacin, but which requires methylation for its metabolism, can induce hepatic damage when administered in high doses (17)(18)(19). In rats consuming choline-deficient diets, high-dose niacinamide has been reported to diminish liver SAM levels, induce fatty liver and DNA singlestrand breaks, and depress creatine synthesis (20)(21)(22), these effects are alleviated by administration of methyl donors.…”

Section: Depletion Of Hepatic Sam As a Mechanism For Niacin Hepatotoxmentioning

confidence: 92%

Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy

McCarty¹

2000

Medical Hypotheses

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The relationship between the ability of pyridine and substituted pyridines to maintain cytochrome P-450 and inhibit protein synthesis in rat hepatocyte cultures

Villa

Hockin

Paine

1980

Biochemical Pharmacology

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Metabolic Effects and Liver Damage after Prolonged Administration of High Doses of Nicotinamide to Rats

Cited by 3 publications

References 1 publication

Nicotinamide overload may play a role in the developmentof type 2 diabetes

Nicotinamide overload may play a role in the developmentof type 2 diabetes

Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy

The relationship between the ability of pyridine and substituted pyridines to maintain cytochrome P-450 and inhibit protein synthesis in rat hepatocyte cultures

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