Nicotinamide counteracts alcohol-induced impairment of hepatic protein metabolism in humans.
We have recently shown that a large amount of wine (750 mL, approximately 70 g of alcohol) markedly impairs postprandial hepatic protein metabolism in healthy subjects. This is probably due to the shift in the intracellular redox state (increased NADH/NAD+) induced by ethanol oxidation. If this hypothesis is true, the administration of nicotinamide (NAD+ precursor) should provide NAD+ in excess and thus correct the NADH/NAD+ abnormalities and prevent the ethanol hepatotoxicity. Whole-body protein metabolism and the fractional secretory rates of hepatic (albumin, fibrinogen) and extra-hepatic (immunoglobulin G, IgG) plasma proteins were measured in the basal postabsorptive and in the absorptive states in 15 healthy subjects, that had been assigned to three groups matched for age and body mass index. During the absorptive state (intragastric meal), the three groups received water (control), 750 mL of wine, or 750 mL of wine + 1.25 g of nicotinamide, respectively. The redox state was estimated by determining the plasma lactate/pyruvate ratio. Compared with the basal state, wine alone increased the lactate/pyruvate ratio twofold and depressed the fractional secretory rates of albumin and fibrinogen (P < 0.01 vs. control and nicotinamide); nicotinamide reduced the effects of wine on the lactate/pyruvate ratio (P < 0.02 vs. wine alone) and prevented the reduction of albumin and fibrinogen secretory rates (P > 0.05 vs. control). These results indicate that nicotinamide counteracts the acute hepatotoxic effects of ethanol by ameliorating the redox state.
Volpi
E
E
Department of Internal Medicine, Endocrine and Metabolic Sciences, University of Perugia, 06126 Perugia, Italy.
Lucidi
P
P
Cruciani
G
G
Monacchia
F
F
Reboldi
G
G
Brunetti
P
P
Bolli
G B
GB
De Feo
P
P
D000328:Adult; D000418:Albumins / Q000096:biosynthesis; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D015992:Body Mass Index; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D007930:Leucine / Q000378:metabolism / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D011773:Pyruvates / Q000097:blood
D000418:Albumins; D001786:Blood Glucose; D007074:Immunoglobulin G; D007328:Insulin; D007773:Lactates; D011506:Proteins; D011773:Pyruvates; D009243:NAD; D009536:Niacinamide; D000431:Ethanol; D005340:Fibrinogen; D007930:Leucine