| dc.description.abstract | D-003 es una mezcla de ácidos alifáticos de cadena muy larga con efectos antiplaquetarios que reducen el colesterol y concomitantes. El sistema microsómico del citocromo P-450 comprende una superfamilia de proteínas presentes en tejidos hepáticos y extrahepáticos que es responsable del metabolismo de muchos fármacos. El presente estudio se llevó a cabo para investigar los efectos de D 003 en las enzimas hepáticas metabolizadoras de fármacos in vivo. Se realizaron dos series experimentales (n = 6 animales / grupo). En la primera serie, las ratas se distribuyeron aleatoriamente en un control y dos grupos tratados con D-003 a 1.000 y 2.000 mg / kg durante 14 días. En el segundo se distribuyeron en un control y tres grupos tratados con D-003 (250, 500 y 1.000 mg / kg) durante 6 meses. Todos los tratamientos se administraron oralmente por sonda gástrica. Las ratas de control se trataron oralmente sólo con vehículo de goma de acacia / agua. El contenido de P-450 microsómico, los citocromos b5, los grupos sulfhidrilo totales, los grupos sulfhidrilo no proteicos y los grupos sulfhidrilo unidos a proteínas así como las actividades de NADPH citocromo c reductasa, aminopirina desmetilasa, dimetilnitrosamina N-desmetilasa, 7-etoxiorresorufina O desmetilación, 7-pentoxyresorufin O-depentilación, y citosólica glutatión S-transferasa. D-003 administrado hasta 2.000 mg / kg o 1.000 mg / kg durante 14 días o 6 meses no afectó las actividades de las enzimas hepáticas metabolizadoras del fármaco investigadas. Se concluye que el D-003 no es metabolizado por el sistema del citocromo hepático y que el riesgo potencial derivado de las interacciones entre D-003 y fármacos concomitantes parece ser bajo. D-003 is a mixture of very-long-chain aliphatic acids with cholesterol-lowering and concomitant anti-platelet effects. The microsomal cytochrome P-450 system comprises a superfamily of proteins present in hepatic and extrahepatic tissues that is responsible for the metabolism of many drugs. The present study was undertaken to investigate the effects of D 003 on in vivo drug-metabolizing hepatic enzymes. Two experimental series (n = 6 animals/group) were performed. In the first series rats were randomly distributed in one control and two groups treated with D-003 at 1,000 and 2,000 mg/kg for 14 days. In the second one they were distributed in one control and three groups treated with D-003 (250, 500, and 1,000 mg/kg) for 6 months. All treatments were orally administered by gastric gavage. Control rats were orally treated only with acacia gum/water vehicle. The content of microsomal P-450, b5 cytochromes, total sulfhydryl groups, nonprotein sulfhydryl groups, and protein-bound sulfhydryl groups as well as the activities of NADPH cytochrome c reductase, aminopyrine demethylase, dimethylnitrosamine N-demethylase, 7-ethoxyresorufin O deethylation, 7-pentoxyresorufin O-depentylation, and cytosolic glutathione S-transferase were assessed. D-003 administered up to 2,000 mg/kg or 1,000 mg/kg during 14 days or 6 months did not affect the activities of the hepatic drug-metabolizing enzymes investigated. It is concluded that D-003 is not metabolized by the liver cytochrome system and that potential risk derived from drug-to-drug interactions between D-003 and concomitant drugs appears to be low. | es_ES |
