Add time:08/26/2019         Source:sciencedirect.com

OBJECTIVES:Nicotinamide methylation followed by urinary excretion of N-METHYLNICOTINAMIDE (cas 114-33-0) increases in cirrhotic patients, despite the derangement of the overall methylation processes in liver disease. The rise in N-methylnicotinamide could depend, at least in part, on a reduced transformation of this molecule into 2-pyridone-5-carboxamide. The aim of this study was to investigate this hypothesis.METHODS:Serum and urinary levels (mean ± SEM) of N-methylnicotinamide and urinary excretion of 2-pyridone-5-carboxamide were measured in 10 healthy controls and 10 patients with liver cirrhosis in basal conditions and after a nicotinamide oral load (1.5 mg/kg body weight).RESULTS:N-methylnicotinamide serum levels increased significantly (p < 0.01) in cirrhotic patients compared to controls, both as basal values (0.43 ± 0.07 nmol/ml; 0.15 ± 0.01) and as area under the curve 5 h after a nicotinamide load (cirrhotics: 562.4 ± 50.5 nmol/ml · min; controls: 314.4 ± 23.8). Twenty-four-hour urinary excretion of N-methylnicotinamide and 2-pyridone-5-carboxamide was also significantly (p < 0.05) increased in cirrhotic patients versus controls, both in basal conditions (N-methylnicotinamide: 82.0 ± 8.4 μmol, 48.8 ± 4.8; 2-pyridone-5-carboxamide: 129.3 ± 23.0, 64.6 ± 9.8) and after a nicotinamide oral load (N-methylnicotinamide: 290.1 ± 23.1, 180.8 ± 7.4; 2-pyridone-5-carboxamide: 694.7 ± 32.5, 391.0 ± 21.9). Moreover, 24 h N-methylnicotinamide/2-pyridone-5-carboxamide ratio was similar in patients and controls (basal: 0.78 ± 0.39, 0.90 ± 0.51; load: 0.42 ± 0.11, 0.48 ± 0.16).CONCLUSIONS:In cirrhotic patients nicotinamide methylation is increased, as shown by the rise in urinary N-methylnicotinamide and 2-pyridone-5-carboxamide that is concurrent and proportional (constant 24-h metabolite ratio). The hyperfunction of this methylating pathway might play a protective role against the toxic effect of intracellular accumulation of nicotinamide deriving from the catabolic state of cirrhosis.

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