Search results for " P4"

Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients.

2013

Background and aims: Lower 25-Hydroxyvitamin D (25[OH]D) serum lev- els have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reduc- tase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Material and methods: Two hundred sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels wer…

A time-course investigation of vitamin A levels and drug metabolizing enzyme activities in rats following a single treatment with prototypic polychlo…

1987

Xenobiotics previously characterized as selective inducers of drug-metabolizing enzymes were chosen to probe possible relationships between enzyme induction and vitamin A metabolism. Liver, kidney and serum retinol and retinyl palmitate levels were investigated in male Sprague--Dawley rats receiving a single i.p. injection of the polychlorinated biphenyls (PCBs), 2,2',5,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl or 2,2',4,4',5,5'-hexachlorobiphenyl (300 mumol/kg) or 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (DDT) (150 mumol/kg). While 2,2',5,5'-tetrachlorobiphenyl, a weak or non-inducer, and 2,2',4,4',5,5'-hexaclorobiphenyl and DDT, phenobarbital-type inducers of cytochrome…

Effect of onion consumption by rats on hepatic drug-metabolizing enzymes

2001

Fruits and vegetables or their natural constituents which increase detoxication enzymes and/or reduce activating enzymes are considered as good candidates to prevent chemically-induced carcinogenesis. In this study, rats were fed a diet supplemented with 20% onion powder for 9 days. Several cytochrome P450 (CYP)s enzymes (CYP 1A, 2B, 2E1, 3A), which are involved in carcinogen activation, were determined by measuring their enzyme activities using specific substrates. In addition, phase II enzymes activities such as UDP-glucuronosyltransferase (UGT) and glutathione S-transferase (GST), involved in detoxication of carcinogens, were measured. Protein levels of CYPs and GST A1/A2, A3/A5, Ml, M2 …

Three cytochrome P450 genes are over-expressed in ryegrass (Lolium sp.) plants resistant to the ALS inhibitors iodosulfuron+mesosulfuron or pyroxsula…

2013

One of the most intense abiotic stresses encountered by arable weeds infesting agricultural fields is herbicide application. Non-target-site based resistance (NTSR), which belongs to the weed herbicide stress response pathways, is an adaptive response to herbicides. Stress response is driven by gene regulation. It follows that NTSR is endowed by differences in the expression of a set of genes between sensitive and resistant plants. We developed an accurate and reliable quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay to detect differences in gene expression in the major grass weed Lolium sp. using two ALS inhibitors (iodosulfuron+mesosulfuron and pyroxsulam). Res…

Cytochrome P450 1A- and stress protein-induction in early life stages of medaka (Oryzias latipes) exposed to trichloroethylene (TCE) soot and differe…

2013

It has previously been shown that trichloroethylene (TCE) soot extracts cause dioxinlike toxic effects in medaka fish (Oryzias latipes) and primary liver cell culture of rainbow trout (Oncorhynchus mykiss). This study examines embryonic and larval induction of cytochrome P450 1A and stress proteins after exposure of medaka embryos to extracts and fractions of TCE combustien-generated aerosols. Embryos were exposed to three concentrations of whole soot extract (WE; 2.7, 7.2 and 18 μg l -1 incomplete combustion by-products), TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, 3 ng l -1 ) and four TCE fractions with different polarity (Fr 1-4; 18 μg l -1 ) for 8 days. Approximately 50% of the embryos w…

The solubilization site of 5,10,15,20-tetrakis-(2,6-dichlorophenyl)-porphyrin-Mn(III) in DPPC vesicles: A spectrophotometric and tensiometric study

2006

The solubilization site of 5,10,15,20-tetrakis-(2,6-dichlorophenyl)-porphyrin-Mn(III) (MnTDPPC) in (L)-alpha-dipalmitoylphosphatidyl choline (DPPC) vesicles was determined in a systematic UV-vis spectrophotometric study. Measurements of the MnTDPPC absorbance have been conducted at constant temperatures (in the interval 30 degrees C <= T <= 48 degrees C) and varying concentrations of phospholipid. In the entire temperature range, the absorption due to MnTDCCP was found to increase with increasing DPPC concentration, until it reaches a plateau value. The data have been analyzed using a pseudo-phase model yielding the binding constant of MnTDCPP to vesicular aggregates. No significant tempera…

An in vitro tool to assess cytochrome P450 drug biotransformation-dependent cytotoxicity in engineered HepG2 cells generated by using adenoviral vect…

2011

Many adverse drug reactions leading to hepatotoxicity are caused by the cytochrome P450-dependent activation of non-toxic drugs or chemicals into reactive metabolites. To this end, adenoviruses were used as a tool to efficiently deliver specific CYP genes into cultured cells (i.e., human hepatoma cell line HepG2). Recombinant-defective adenoviral vectors encoding for genes CYP3A4 (Adv-CYP3A4), CYP2E1 (Adv-CYP2E1), CYP2A6 (Adv-CYP2A6) and CYP1A2 (Adv-CYP1A2) were used to confer specific CYP drug metabolic capabilities to HepG2 cells. Upgraded cells transiently expressed single specific cytochrome P450 enzymatic activities in terms of the number of the infecting virus particles used in their …

2019

The olfactory epithelium is continuously exposed to exogenous chemicals, including odorants. During the past decade, the enzymes surrounding the olfactory receptors have been shown to make an important contribution to the process of olfaction. Mammalian xenobiotic metabolizing enzymes, such as cytochrome P450, esterases and glutathione transferases (GSTs), have been shown to participate in odorant clearance from the olfactory receptor environment, consequently contributing to the maintenance of sensitivity toward odorants. GSTs have previously been shown to be involved in numerous physiological processes, including detoxification, steroid hormone biosynthesis, and amino acid catabolism. The…

Phosphorylation of cytochrome P450 isoenzymes in intact hepatocytes and its importance for their function in metabolic processes.

1990

Recent data show that besides the well-known long-term regulation of cytochrome P450-dependent monooxygenase activity by induction there also exists a fast regulation by phosphorylation. This phosphorylation occurs when purified cytochromes P450 are combined with purified protein kinases, and also in intact cells. This process is donor- and acceptor-selective leading to phosphorylation of defined isoenzymes by defined protein kinases. This in turn leads to fast and marked changes in metabolism which are selective for given substrates and regio- and stereo-selective for given positions. This in turn is selectively and differentially influenced by the individual control of the protein kinase …

Significance of Posttranslational Modification of Drug Metabolizing Enzymes by Phosphorylation for the Control of Carcinogenic Metabolites

1995

The total activity of foreign compound metabolizing enzymes may change by altering the amount or the specific activity of the enzyme by induction or repression, or by activation or inhibition. The important contribution of enzyme induction is well known (Conney 1982, Oesch 1986, Nebert and Jones 1989). This is a relatively slow process which requires the biosynthesis of the enzyme protein. The possibility of a faster regulation of foreign compound metabolism by posttranslational modification by phosphorylation of an already preexisting protein molecule has only recently received attention. A central role in the metabolism of foreign compounds is played by the cytochrome P450-dependent monoo…