We reported that norepinephrine and angiotensin II (Ang II) activate the Ras/mitogen-activated protein (MAP) kinase pathway primarily through the generation of cytochrome P450 (CYP450) metabolites. The purpose of the present study was to determine the contribution of Ras and CYP450 to Ang II-dependent hypertension in rats. Infusion of Ang II (350 ng/min for 6 days) elevated mean arterial blood ...

Enhanced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and other endothelial cell adhesion molecules (ECAMs) are associated with the onset and progression of inflammatory bowel disease (IBD). We show in this study that two cytochrome p-450 (CYP450) inhibitors from Citrus paradis (grapefruit), bergamottin, and 6',7'-dihydroxybergamottin (DHB) block tumor necrosis factor (TN...

Previously, we have reported that the coronary reactive hyperemic response was reduced in adenosine A2A receptor-null (A2AAR?/?) mice, and it reversed by soluble epoxide hydrolase (sEH) inhibitor. However, is unknown aortic vascular response, therefore, hypothesized A2AAR-gene deletion mice affects adenosine-induced increase sEH A1 receptor (A1AR) activities. A2AAR?/? showed an sEH, AI AR CYP45...

Inhibition of cytochrome P450 (CYP450) enzymes can result in potential clinical drug-drug interaction liabilities. Because of the safety and economic concern leading to clinical failure or product withdrawal, screening of lead molecules for CYP450 inhibition potential is nowadays conducted much earlier in the drug development process. At this early phase, a large number of lead molecules are in...

We recently reported that norepinephrine and angiotensin II activate the Ras/mitogen-activated protein (MAP) kinase pathway through generation of a cytochrome P450 (CYP450) and lipoxygenase metabolites. The purpose of this study was to determine the contribution of Ras/MAP kinase to deoxycorticosterone acetate (DOCA)-salt-induced hypertension in rats. Administration of DOCA and 1% saline drinki...

Liver cirrhosis, a progressive disease, presents no obvious symptoms in the early stage. So far, no comprehensive study has focused on the dynamic changes of liver function and the metabolic ability of CYP450 enzymes. In this study, thirty-two Sprague-Dawley Rats were randomly divided into two groups: Control-group (n=10) and cirrhosis-group (n=22). The cirrhotic rat model was developed by subc...

Cytochrome P450 (CYP450) is a major drug-metabolizing enzyme system mainly distributed in liver microsomes and involved the metabolism of many endogenous substances (such as fatty acids arachidonic acids), exogenous compounds drugs, toxicants, carcinogens, procarcinogens). Due to similarity structures catalytic functions between CYP450 isoforms, lack effective selective detection tools greatly ...

To investigate the auto-induction of cytochrome P450 (CYP450) by Chloroxoquinoline (CXL), a novel anticancer drug. Three experiments related to the induction of CYP450 were performed: a) In vitro use of the rat fresh hepatocytes model; b) In vivo 'cocktail' of CYP450 probe model; c) Pharmacokinetic (PK) study of the single and multiple doses. Some typical CYP enzyme probes and inducers were use...

PURPOSE To examine the relation between variant alleles in 3 CYP450 genes (CYP2D6, CYP2C9 and CYP2C19), interacting drugs and akathisia in subjects referred to a forensic psychiatry practice in Sydney, Australia. PATIENTS AND METHODS This paper concerns 10/129 subjects who had been referred to the first author's practice for expert opinion or treatment. More than 120 subjects were diagnosed w...

The aim of this study was to improve knowledge about transplacental transfer of an environmentally relevant PCB mixture by evaluating congener levels in livers and brains of rat dams and fetuses after maternal exposure, and correlating them to the levels of CYP450 and P-glycoprotein, involved in biotransformation and xenobiotics export, respectively. Pregnant dams were injected daily from gesta...