ABSTRACT
Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-promoting phytochemicals. There are any reports about the effects of kale ingestion on the chemoprevention function and mechanism, but the interactions between kale and drugs have not been researched. We investigated the effects of kale intake on cytochrome P450 (CYP) metabolism by using cocktail probe drugs, including midazolam (for CYP3A4), caffeine (for CYP1A2), dextromethorphan (for CYP2D6), tolbutamide (for CYP2C9), omeprazole (for CYP2C19), and chlorzoxazone (for CYP2E1). Cocktail drugs were administered into rats treated with kale and cabbage (2000 mg/kg) for a week. The results showed that kale intake induced a significant increase in plasma levels and the AUC of midazolam, caffeine, and dextromethorphan. In addition, the plasma concentration and AUC of omeprazole tended to increase. Additionally, no almost differences in the mRNA expression levels of CYP enzymes in the liver were observed. In conclusion, kale ingestion was considered to have an inhibitory effect on the activities of CYP3A4, 1A2, 2D6, and 2C19 for a reason competitive inhibition than inhibitory changes in the mRNA expressions.
Subject(s)
Brassica/metabolism , Cytochrome P-450 Enzyme System/metabolism , Enzyme Inhibitors/pharmacology , Midazolam/pharmacokinetics , Administration, Oral , Animals , Area Under Curve , Caffeine/pharmacokinetics , Chlorzoxazone/pharmacokinetics , Cytochrome P-450 CYP1A2 , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP2D6 Inhibitors , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP2E1/metabolism , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/genetics , Cytochromes/antagonists & inhibitors , Cytochromes/genetics , Cytochromes/metabolism , Dextromethorphan/pharmacokinetics , Herb-Drug Interactions , Liver/enzymology , Metabolic Clearance Rate , Omeprazole/pharmacokinetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Tolbutamide/pharmacokineticsABSTRACT
Kale is a cruciferous vegetable (Brassicaceae) that contains a large amount of health-promoting phytochemicals. The chronic ingestion of cabbage of the same family is known to accelerate conjugating acetaminophen (AA) and decrease the plasma AA level. Therefore, we examined to clarify the effects of kale on the pharmacokinetics of AA, its glucuronide (AA-G) and sulfate (AA-S). AA was orally administered to rats pre-treated with kale or cabbage (2000 mg/kg/day) for one week. Blood samples were collected from the jugular vein, and the concentrations of AA, AA-G and AA-S were determined. In results, kale ingestion induced an increase in the area under the concentration-time curve (AUC) and a decrease in the clearance of AA, whereas cabbage had almost no influence. In addition, there were significant differences in the AUC of AA-G between the control and kale groups. mRNA expression levels of UDP-glucuronosyltransferases, the enzymes involved in glucuronidation, in the kale group were significantly higher than those in the control group. In conclusion, kale ingestion increased the plasma concentrations of both AA and AA-G. The results suggest that kale ingestion accelerates the glucuronidation of AA, but an increase of plasma AA levels has a different cause than the cause of glucuronidation.
Subject(s)
Acetaminophen/pharmacokinetics , Analgesics, Non-Narcotic/pharmacokinetics , Brassica , Food-Drug Interactions , Acetaminophen/blood , Analgesics, Non-Narcotic/blood , Animals , Base Sequence , Chromatography, Liquid , DNA Primers , Glucuronosyltransferase/genetics , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain ReactionABSTRACT
While brain development during embryogenesis has been extensively studied in precocial birds, there is no information available on altricial birds. Thus, the concentrations of the catecholamines norepinephrine (NE), epinephrine (E), and dopamine (DA), and the dopaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA) were determined at several stages during the late embryonic period (E13, E14, E15, E16, E17 and E18) and the day-of-hatch (P0) in the pigeon telencephalon, cerebellum, optic lobe, and brainstem. The concentrations of all catecholamines were higher than those reported in chicken embryos. During embryogenesis, NE, E, DOPAC and HVA concentrations in the various brain parts increased throughout embryonic development until shortly before hatching at which time they decreased. DA, however, continued to increase through hatching in the brainstem, and the changes in DA concentrations varied in several brain parts. In conclusion, catecholamine concentrations in the various brain parts tended to increase with embryonic age, and the concentrations were higher than those in chickens. Furthermore, brain catcholamine metabolism changed at hatch in pigeons.
Subject(s)
Brain/embryology , Catecholamines/metabolism , Columbidae/embryology , Animals , Brain/growth & development , Brain/metabolism , Brain Chemistry , Columbidae/growth & development , Columbidae/metabolism , Dopamine/metabolism , Epinephrine/metabolism , Norepinephrine/metabolismABSTRACT
Ghrelin is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. Ghrelin stimulates feeding in rats, however, intracerebroventricular (i.c.v.) injection of rat ghrelin inhibits feeding of neonatal chicks. In the present study, the effect of i.c.v. injection of different ghrelins including chicken and bullfrog ghrelin, and synthetic GH-releasing peptide (GHRP) on feeding of neonatal chicks was investigated. Chicken ghrelin strongly suppressed feeding. To compare the inhibitory effect, chicken and rat ghrelin were examined. The suppressive effect of feeding by chicken and rat ghrelin was almost identical. Bullfrog ghrelin contains a change in the acylated amino acid from Ser to Thr, strongly suppressed feeding. The i.c.v. injection of GHRP-2 (KP-102), a synthetic GHS, also inhibited feeding. These results indicate that the chicken GHS receptor is affected by several forms of GHS, and that food intake of neonatal chicks is inhibited by GHS receptor agonists.
