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Tests to evaluate the liver energy reserve and hepatocyto-protective effect of drugs in man.
No full textTests to evaluate the liver energy reserve and hepatocyto-protective effect of drugs in man.
No full textNicotinamide methylation and hepatic energy reserve: a study by liver perfusion in vitro.
No full textAbstract: Background/Aims: The synthesis of pyridine nucleotides from nicotinamide requires adenosine triphosphate. In man when exogenous nicotinamide is poorly utilized in this synthesis, the excess follows a dissipative metabolic pathway and is excreted in urine as N-methylnicotinamide. In human cirrhosis N-methylnicotinamide serum levels are higher than normal, in basal condition and after nicotinamide oral load, The aim of this study was to verify N-methylnicotinamide production in relation to hepatic content of adenosine triphosphate during in vitro perfusion of rat liver, in normal conditions and after adenosine triphosphate depletion by metabolic stress.
Methods: ''Stress'' was obtained by pre-washing with saline for 15 min before the perfusion with nutritive medium.
Results: The adenosine triphosphate decrease in the stressed liver was 38% after pre-washing with saline and 80% at the end of nutritive perfusion, In control liver the corresponding decreases were 1% after pre-washing with nutritive medium and 65% at the end of perfusion with the same medium, The total nicotinamide adenine dinucleotide decreases were 44% and 56% in the stressed liver, and 19% and 52% in the control liver, The output levels of N-methylnicotinamide at 90 min of rat liver nutritive perfusion were 31.50+/-4.72 nmol/g for normal liver and 66.40+/-13.17 for stressed liver (p<0.001). Liver adenosine triphosphate was inversely related to N-methylnicotinamide production (r=0.93; p<0.001).
Conclusions: These data suggest that nicotinamide methylation may be enhanced when there is hepatic adenosine triphosphate decrease and energy failure induced by hypoxia or metabolic stress, similar to that obtained in vitro by saline washing before perfusion with nutritive medium, This study shows that the evaluation of N-methylnicotinamide production in man (before and after nicotinamide load) might be useful to explore the energy state of diseased live
Nicotinamide methylation and hepatic energy reserve.
No full textIn liver diseases the reduction of hepatic energy reserve may affect many metabolic pathways that require ATPR e.g. the synthesis of pyridine nucleotides from nicotinamide (NAM). When exogenous NAM is poorly utilized in this synthesis, it follows a dissipative metabolic pathway and is excreted in urine as N-methyinicotinamide (NMN).
Recently we reported a significant increase of NMN production and excretion in cirrhotic patients in basal condition and after NAM oral load. The aim of this study was to verify NAM methylation in relation to liver content of ATP and glycogen during rat liver in vitro perfusion with or without metabolic stress. The stress was obtained by a 15 min delay in Krebs medium perfusion of isolated liver. The metabolic stress significantly reduced the liver content of ATP The production of NMN in the stressed rat liver is significantly higher than in normal liver. The NAM liver methylation is inversely related to ATP (r = -0.74; p < 0.01) and glycogen (r = -0.53; p < 0.05) levels.
In conclusion this study suggests that the increase of NMN production in cirrhotic patients may depend on the energy crisis of liver cel
The metabolism of nicotinamide in human liver cirrhosis: a study on N-methylnicotinamide and 2-pyridone-5-carboxamide production.
No full textOBJECTIVES: Nicotinamide methylation followed by urinary excretion of N-methylnicotinamide 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 x 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 micromol, 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 cirrhosi
Nicotinamide methylation and hepatic energy reserve: a study by liver perfusion in vitro.
No full text
Nicotinamide methylation and hepatic energy reserve: a study by liver perfusion in vitro.
No full text- …
