Abstract
We have recently shown that a large amount of wine (750 mL, ∼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.
Highlights
We have recently shown that a large amount of wine (750 mL, Ç70 g of alcohol) markedly impairs postprandial hepatic protein metabolism in healthy subjects
This hypothesis is consistent with studies in dogs, demonstrating that hepatic secreted plasma proteins may serve as an important source of amino acids for protein synthesis in muscle and other peripheral tissues (Elwyn 1970, Elwyn et al 1968), and in elderly humans, in whom serum albumin concentration significantly associates with muscle mass (Baumgartner et al 1996)
Fibrinogen and immunoglobulin G (IgG) tracer incorporation rates (DSA/Dt) and fractional secretory rates (FSR) in normal humans in the postabsorptive period and during the intragastric administration of a mixed meal combined with the ingestion of either water or wine with (NA) or without (W) the administration of nicotinamide1
Summary
We have recently shown that a large amount of wine (750 mL, Ç70 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. One potential nutritional role of albumin is as a temporary storage pool of amino acids, protecting some fraction of ingested amino acids from irreversible oxidation and ensuring their delivery to peripheral tissues for utilization in protein synthesis days after their intake This hypothesis is consistent with studies in dogs, demonstrating that hepatic secreted plasma proteins may serve as an important source of amino acids for protein synthesis in muscle and other peripheral tissues (Elwyn 1970, Elwyn et al 1968), and in elderly humans, in whom serum albumin concentration significantly associates with muscle mass (Baumgartner et al 1996). Total leucine Ra3 Ig leucine infusion rate Endogenous leucine Ra Leucine oxidation rate Nonoxidative leucine disposal Net leucine balance
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