Estudios científicos
Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: a review of the literature.
Abstract:
Sulfotransferase catalyzes the transfer of sulfate, donated by 3'-phosphoadenosine-5'-phosphosulfate, to an acceptor substrate that may be a hydroxy group or an amine group. Man is exposed daily to drugs and dietary chemicals that can inhibit sulfotransferase activity. The aim of this study was to review the literature concerning the inhibition of sulfotransferases by drugs and dietary chemicals in the human liver and duodenum. The IC50 value of mefenamic acid for human liver phenol sulfotransferase (SULT 1A1) was 0.02 microM and for human liver catechol sulfotransferase (SULT1A3) 76 microM with a SULT 1A3/SULT1A1 ratio for the IC50 of 3,800. Mefenamic acid is therefore a potent and selective inhibitor of human liver SULT1A1. The IC50 values of mefenamic acid for the sulfation rates of (-)-salbutamol and (-)-apomorphine were 4 orders of magnitude greater in the human duodenum than in the liver. Salicylic acid inhibited the sulfation of (-)-apomorphine in human liver with an IC50 of 54 gM but did not inhibit the sulfation of (-)-apomorphine in human duodenum. Quercetin, a flavonoid present in edible fruit, vegetable and wine, was a potent inhibitor of human liver SULT1A1 and estrogen sulfotransferase (EST) activities and the sulfation of resveratrol. Quercetin inhibited the sulfation of dopamine, (-)-salbutamol, minoxidil and paracetamol and the IC50 values were 1 – 2 orders of magnitude greater in human duodenum than in the liver. In conclusion, mefenamic acid, salicylic acid and quercetin inhibit SULT1A1 whereas SULT1A3 is relatively resistant to the inhibition by these compounds. Under particular circumstances, human duodenum sulfotransferase is more resistant than liver sulfotransferase to the inhibition by mefenamic acid, salicylic acid and quercetin.
Comentarios divulgativos:
La Sulfotransferasa cataliza la transferencia de sulfato, donados por 3'-fosfoadenosina-5'-fosfosulfato, a un sustrato aceptor que puede ser un grupo hidroxilo o un grupo amino. El hombre está expuesto diariamente a los medicamentos y productos químicos que pueden inhibir la actividad de la sulfotransferasa. El objetivo de este estudio fue revisar la literatura respecto a la inhibición de sulfotransferasas por las drogas y productos químicos alimentarios en el hígado humano y el duodeno. La quercetina, un flavonoide presente en las frutas vegetales comestibles, y el vino, era un potente inhibidor de hígado humano de SULT1A1 sulfotransferasa actividades y la sulfatación de resveratrol. La quercetina inhibe la sulfatación de la dopamina, (-)-salbutamol, minoxidil y el paracetamol y los valores de IC50 fueron 1 a 2 órdenes de magnitud mayor en el duodeno de humanos que en el hígado. En conclusión, el ácido mefenámico, ácido salicílico y la quercetina inhibe a SULT1A1 SULT1A3 mientras que es relativamente resistente a la inhibición de estos compuestos. Bajo determinadas circunstancias, la sulfotransferasa del duodeno humano es más resistente que la sulfotransferasa del hígado a la inhibición por el ácido mefenámico, ácido salicílico y quercetina.
