Garlic extracts have been shown to decrease drug exposure for saquinavir, a P-glycoprotein and cytochrome P450 3A4 substrate. In order to explore the underlying mechanisms and to study the effects of garlic on pre-systemic drug elimination, healthy volunteers were administered garlic extract for 21 days. Prior to and at the end of this period, expression of duodenal P-glycoprotein and cytochrom...

Expression and activities of cytochrome P450 enzymes are down-regulated in the liver during the host response to inflammation or infection, leading to alterations in drug clearance and toxin activation. This review focuses on recent studies on the mechanisms of this down-regulation, as well as the cytokines and cell types involved. Possible reasons for cytochrome P450 down-regulation are discus...

The cytochrome P450 monooxygenases are an important metabolic system whose level of activity can be influenced by several dietary constituents. We examined the effects of six known P450 inducers on the levels of total cytochromes P450, cytochrome b(5), and six monooxygenase activities in adult German cockroaches. In addition, the levels of CYP6L1 and CYP9E2 mRNA were also investigated. Phenobar...

Cytochrome P450 (P450) enzymes primarily catalyze mixed-function oxidation reactions, plus some reductions and rearrangements of oxygenated species, e.g. prostaglandins. Most of these reactions can be rationalized in a paradigm involving Compound I, a high-valent iron-oxygen complex (FeO), to explain seemingly unusual reactions including ring couplings, ring expansion and contraction, and fusio...

Ethanol-inducible cytochrome P450 2E1 (CYP2E1) involved in the metabolism of gluconeogenetic precursors and some cytotoxins is distinguished from other cytochrome P450 enzymes by its rapid turnover (in vivo half-life of 4-7 h), with ligands to the haem iron, both substrates and inhibitors, stabilizing the protein. CYP2E1 is also known to have a high oxidase activity in the absence of substrate,...

Introduction: Rhabdomyolysis-induced myoglobinuric acute renal failure accounts for about 10-40% of all cases of acute renal failure (ARF). Iron and Cytochrome P450 are involved in the pathogenesis of myoglobinuric ARF. The Aim of this Study: To explore the effect of cimetidine as a potent cytochrome P450 inhibitor on myoglobinuric ARF in rat. Methods: Twenty four rats were divided into 3 group...

Clopidogrel is a thienopyridine platelet antagonist that irreversibly inhibits the binding of adenosine diphosphate to platelet receptors, ultimately leading to inhibition of platelet aggregation. Clopidogel is a prodrug requiring hepatic bioactivation via cytochrome P450 isozymes (CYP2C19, CYP3A4, CYP3A5) to its pharmacologically active form. Inhibition of cytochrome P450 may interfere with me...