RESUMEN
It is thought that eating habits induces individual variation in intestinal absorption and metabolism of drugs. The objective of this research was to clarify the influence of vegetables juices on CYP3A4 activity, which is an important enzyme in intestine. Five vegetables juices (VJ-o, Kagome Original(®); VJ-g, Kagome 30 kinds of vegetables and fruits(®); VJ-p, Kagome Purple vegetables(®); VJ-r, Kagome Sweet Tomato(®); and VJ-y, Kagome Fruity Salada(®); KAGOME Co., Ltd., Aichi, Japan) were centrifuged (1630×g, 10 min) and filtered using filter paper and 0.45-µm membrane filters. In this study, recombinant CYP3A4 and LS180 cells were used for the evaluation of CYP3A4 activity. The metabolisms to 6ß-hydroxytestosterone by recombinant CYP3A4 were significantly inhibited by VJ-o, VJ-g, and VJ-y in a preincubation time-dependent manner, and CYP3A4 activity in LS180 cells were significantly inhibited by VJ-o and VJ-y. These results show that the difference in ingestion volume of vegetable juices and vegetables might partially induce individual difference in intestinal drug metabolism.
Asunto(s)
Citocromo P-450 CYP3A/metabolismo , Jugos de Frutas y Vegetales , Hidroxitestosteronas/antagonistas & inhibidores , Línea Celular Tumoral , Interacciones Alimento-Droga , Humanos , Hidroxitestosteronas/metabolismo , Proteínas Recombinantes/metabolismo , VerdurasRESUMEN
The progesterone 17alpha-hydroxylase activity, which is one of the steroidogenic enzymes in rat testis microsomes, was significantly inhibited by crude marijuana extracts from Delta(9)-tetrahydrocannabinolic acid (THCA)- and cannabidiolic acid (CBDA)-strains. Delta(9)-Tetrahydrocannabinol, cannabidiol and cannabinol also inhibited the enzymatic activity with relatively higher concentration (100-1000 microM). Testosterone 6beta- and 16alpha-hydroxylase activities together with androstenedione formation from testosterone in rat liver microsomes were also significantly inhibited by the crude marijuana extracts and the cannabinoids. Crude marijuana extracts (1 and 10 microg/ml) of THCA strain stimulated the proliferation of MCF-7 cells, although the purified cannabinoids (THC, CBD and CBN) did not show significant effects, such as the extract at the concentration of 0.01-1000 nM. These results indicate that there are some metabolic interactions between cannabinoid and steroid metabolism and that the constituents showing estrogen-like activity exist in marijuana.
Asunto(s)
Androstenodiona/metabolismo , Cannabis/toxicidad , Alucinógenos/toxicidad , Testosterona/metabolismo , Androstenodiona/antagonistas & inhibidores , Animales , Cannabinoides/toxicidad , Cannabinol/toxicidad , Cannabis/química , Línea Celular Tumoral , Inhibidores Enzimáticos del Citocromo P-450 , Dronabinol/toxicidad , Femenino , Alucinógenos/química , Antagonistas de Hormonas/metabolismo , Antagonistas de Hormonas/toxicidad , Hidroxitestosteronas/antagonistas & inhibidores , Hidroxitestosteronas/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Hojas de la Planta/toxicidad , Ratas , Ratas Sprague-Dawley , Esteroide 17-alfa-Hidroxilasa/antagonistas & inhibidores , Esteroide Hidroxilasas/antagonistas & inhibidores , Testículo/efectos de los fármacos , Testículo/enzimología , Testículo/metabolismoRESUMEN
The etiology of male-pattern alopecia is explained as an interrelationship of three factors, genetic--a single dominant sex-limited gene; endocrine--dihydrotestosterone is the specific hormone responsible; and age. Other factors previously used to explain male-pattern alopecia are debunked. Treatment today is directed in the area of endocrinology, basically using either antiandrogens that block 5-alpha-reductase, thus preventing the formation of dihydrotestosterone, or steroids that interfere with dihydrostestosterone cytosol--nuclear binding protein expression.