Search results for "cytochrome p450"
showing 10 items of 135 documents
The effects of short-term glyphosate-based herbicide exposure on insect gene expression profiles
2023
Glyphosate-based herbicides (GBHs) are the most frequently used herbicides worldwide. The use of GBHs is intended to tackle weeds, but GBHs have been shown to affect the life-history traits and antioxidant defense system of invertebrates found in agroecosystems. Thus far, the effects of GBHs on detoxification pathways among invertebrates have not been sufficiently investigated. We performed two different experiments—1) the direct pure glyphosate and GBH treatment, and 2) the indirect GBH experiment via food—to examine the possible effects of environmentally relevant GBH levels on the survival of the Colorado potato beetle (Leptinotarsa decemlineata) and the expression profiles of their deto…
Metabolism and bioactivation of toxicants in the lung. The in vitro cellular approach.
2005
Lung is a target organ for the toxicity of inhalated compounds. The respiratory tract is frequently exposed to elevated concentrations of these compounds and become the primary target site for toxicity. Occupational, accidental or prolonged exposure to a great variety of chemicals may result in acute or delayed injury to cells of the respiratory tract. Nevertheless, lung has a significant capability of biotransforming such compounds with the aim of reducing its potential toxicity. In some instances, the biotransformation of a given compound can result in the generation of more reactive, and frequently more toxic, metabolites. Indeed, lung tissue is known to activate pro-carcinogens (i.e. po…
Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes
2015
The adverse effects to humans and environment of only few chemicals are well known. Absorption, distribution, metabolism, and excretion (ADME) are the steps of pharmaco/toxicokinetics that determine the internal dose of chemicals to which the organism is exposed. Of all the xenobiotic-metabolizing enzymes, the cytochrome P450 (CYP) enzymes are the most important due to their abundance and versatility. Reactions catalyzed by CYPs usually turn xenobiotics to harmless and excretable metabolites, but sometimes an innocuous xenobiotic is transformed into a toxic metabolite. Data on ADME and toxicity properties of compounds are increasingly generated using in vitro and modeling (in silico) tools.…
Effects of garlic powders with varying alliin contents on hepatic drug metabolizing enzymes in rats
2003
International audience; The anticarcinogenic effect of garlic has been demonstrated in both epidemiologic and experimental studies. In this study, possible mechanisms involved in the anticarcinogenic effect of garlic consumption were assessed by determining its capacity to alter drug metabolizing enzymes, in relation with its alliin content. Rats were fed a diet for 2 weeks containing 5% garlic powders produced from bulbs grown on soils with different levels of sulfate fertilization and therefore containing differing amounts of alliin. Activities of several hepatic enzymes, which are important in carcinogen metabolism such cytochromes P450 (CYP) and phase II enzymes, were determined. Garlic…
Evaluation of the genotoxic and cytochrome P450 monooxygenase‐inhibitory potential of dicuran on procaryotic and eucaryotic test systems
2000
The effect of the herbicide Dicuran 500 FL (formulated product) on the phenotypical and genotypical changes in procaryotic and eucaryotic organisms was investigated using short-term tests for detecting genotoxins. Since pesticides discharged in the water environment can modulate the mixed-function monooxygenases (MFO) detoxification system of water organisms, the in vivo and in vitro effects of Dicuran on hepatic cytochrome P450 (cyt P450) monooxygenase activities were also examined in juvenile carp (Cyprinus carpio L.). By measuring the activities of MFO in experimental carp exposed to Dicuran an attempt was made to establish whether Dicuran could be bioactivated by MFO into ultimate mutag…
Modulation of cytochrome P450 1A in sea bass liver by model substances and seawater extracts
1998
Abstract 1. 1. Immunochemical and catalytic assays for cytochrome P450 1A induction in liver of sea bass Dicentrarchus labrax treated with different model substances and organic seawater extracts have been performed. 2. 2. Ethoxyresorufin-O-deethylase (EROD) activities in fish liver were elevated by Arochlor 1254 (Aro), 3-methylcholanthrene (MC) and β-naphtoflavone (βNF). but not by phenobarbital (PB) treatment. 3. 3. Elevated levels of P450 1A protein followed by induction of EROD activity were detected only in βNF treated fish. 4. 4. Treatment of fish with organic seawater extracts revealed that there is no simple correlation between EROD activities and its catalyst P450 1A level. Seawate…
Investigating the Role of the Microsomal Epoxide Hydrolase Membrane Topology and Its Implication for Drug Metabolism Pathways
1996
The microsomal epoxide hydrolase (mEH) catalyzes the hydrolysis of reactive epoxides which are formed by the action of cytochromes P450 from xenobiotics. In addition the mEH has been found to mediate the transport of bile acids. For the mEH it has been shown that it is cotranslationally inserted into the endoplasmic reticulum. Here we demonstrate that the amino-terminal twenty amino acid residues of this protein serve as its single membrane anchor signal sequence and that the function of this sequence can be also supplied by a cytochrome P450 (CYP2B1) anchor signal sequence.
Multifaceted contributions of epidermal langerhans cells to cutaneous carcinogenesis.
2015
Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAH) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LC) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LC rapidly internalize an…
Charged Tags for the Identification of Oxidative Drug Metabolites Based on Electrochemistry and Mass Spectrometry
2020
Abstract Most of the active pharmaceutical ingredients like Metoprolol are oxidatively metabolized by liver enzymes, such as Cytochrome P450 monooxygenases into oxygenates and therefore hydrophilic products. It is of utmost importance to identify the metabolites and to gain knowledge on their toxic impacts. By using electrochemistry, it is possible to mimic enzymatic transformations and to identify metabolic hot spots. By introducing charged‐tags into the intermediate, it is possible to detect and isolate metabolic products. The identification and synthesis of initially oxidized metabolites are important to understand possible toxic activities. The gained knowledge about the metabolism will…
Effect of polybrominated biphenyls on bromobenzene lethality in mice.
1977
Polybrominated biphenyls (PBBs) are inducers of hepatic microsomal cytochrome P450 and P1 450 in rats and mice. The purpose of this study was to determine, in mice, the effect of PBBs on the lethality of the hepatotoxin bromobenzene. Female NMRI mice were administered a single ip injection of 150 mg/kg PBBs and other mice received phenobarbital (PB), 100 mg/kg daily for 3 days, or 3‐methylcholanthrene (MC), 20 mg/kg daily for 3 days. At 24 hr after PB or MC and 24, 48, and 96 hr after PBBs animals received 3,150 mg/kg bromobenzene ip (LD85) and the time to death was recorded. Both PB and MC enhanced bromobenzene lethality and decreased the median time to death (LT50) from 23 hr in controls …