Absorción in vivo de oligómeros de epicatequina

Identifier:  TDX:433

Handle: https://hdl.handle.net/20.500.11797/TDX433

Authors:  García Ramírez, Bernardino

Abstract:
In the last years, a great interest in the existing relation between moderate wine consumption and health has appeared. The beneficial effects associated to the moderate wine consumption are due mainly to the presence of phenolic compounds in wine. Nevertheless, the absorption, sanguineous transport, tissue distribution, metabolism and excretion of phenolic compounds in general (and procyanidins in particular) remain unknown due to methodological problems associated with this type of compounds. Procyanidins are oligomeric compounds present in red wine in high concentrations that exert beneficial physiological effects for the health. However, so that these compounds can develop these beneficial effects, they must be absorbed from the diet. Therefore, this PhD thesis is based on the synthesis and radiolabel of epicatechin oligomers and in the study of the absorption of these compounds in rats. Epicatechin oligomers synthesis is carried out simulating a series of polymerization reactions that take place during the red wine aging process between procyanidins and acetaldehyde. The simulation on laboratory scale of this type of reactions between epicatechin (monomer) and acetaldehyde allowed the synthesis of oligomeric structures with a condensation degree between 2 and 10 (when acetaldehyde in defect was added to the reaction medium) and polymers of 16 epicatechin units and trimers (when acetaldehyde in excess was added to the reaction medium). Besides, the use of radiolabelled acetaldehyde allowed to radiolabel the epicatechin oligomers with 14C. On the other hand, the stability of these compounds in acid surroundings, similar to the existing one in the stomach, and basic surroundings, similar to which exists in the small intestine, was evaluated. The obtained results indicated that epicatechin oligomers were stable in acid surroundings, whereas they were not stable in basic surroundings. In order to study the absorption in vivo in rats of the synthesized epicatechin oligomers, 50 mg of epicatechin oligomers were administered orally by direct stomach intubation to male Wistar rats. The presence of a dimeric structure formed by two epicatechins linked by an ethyl bridge was detected in the plasma of these experimentation animals. In addition, it was verified that the maximum plasma concentration of this dimeric compound was reached two hours after the administration of epicatechin oligomers to the rats. Moreover, the presence of this dimeric compound in the liver of these animals was also detected, what indicated that the liver was a target organ of procyanidins in accordance with previous results obtained by our investigation group, that had detected changes at hepatic gene expression level and hepatic metabolism level. The presence of the epicatechin dimer in the liver is an important finding, because in the bibliography is not described the presence of these compounds in the liver and, in addition, the changes in the liver previously commented and attributed to the procyanidins could have been due to the direct interaction of these compounds with signalling and/or regulatory proteins present in this organ.