Search results for "CYP"
showing 10 items of 480 documents
In vivo studies on the antiandrogenic effects of cimetidine versus cyproterone acetate in rats
1981
To investigate the antiandrogenic action of cimetidine in vivo, prostatic androgen uptake and metabolism, spermatogenesis, morphology of the prostate and testes, and plasma hormone levels were studied using Sprague-Dawley rats, and the results were compared with the effects of cyproterone acetate or castration. Cimetidine and cyproterone acetate caused significant reduction in the weights of the ventral prostate and testes. The changes of ventral prostate were accompanied by a dose-related epithelial atrophy. No adverse effect on spermatogenesis was observed after treatment with cimetidine at daily doses of 50 mg/kg or cyproterone acetate of 10 mg/kg. Although cimetidine treatment induced a…
The predictability of helminth community structure in space: a comparison of fish populations from adjacent lakes
2002
Patterns in helminth community structure can suggest that various processes are acting to shape parasite communities into organised, non-random assemblages of species. It is not clear, however, whether a pattern observed in one host population at one time would be observed again at another time, or at the same time in a different but comparable host population. Here, we test the repeatability of parasite community structure in space, and to a lesser extent time, with data on helminth parasites of two fish species, perch Perca fluviatilis and roach Rutilus rutilus, collected in different seasons from four adjacent lakes in Central Finland. Since populations of the same fish species harbour t…
Brain metabolism of ethanol and alcoholism: an update.
2007
It has long been suggested that some of the neuropharmacological, neurochemical and behavioural effects of ethanol are mediated by its first metabolite, acetaldehyde. In spite of the well documented psychoactivity of acetaldehyde, the precise role of this compound in alcohol abuse remains a matter of intense debate among scientists devoted to the study of alcoholism. Very frequently, the main drawback has been related to the presence of adequate levels of acetaldehyde or its derivatives inside the brain after ethanol ingestion. Since penetration into the central nervous system from blood of peripherically derived acetaldehyde is very low due to the high aldehyde dehydrogenase activity at th…
Efavirenz and the CNS: what we already know and questions that need to be answered
2015
The NNRTI efavirenz has long been one of the most frequently employed antiretroviral drugs in the multidrug regimens used to treat HIV infection, in accordance with its well-demonstrated antiretroviral efficacy and favourable pharmacokinetics. However, growing concern about its adverse effects has sometimes led to efavirenz being replaced by other drugs in the initial treatment selection or to switching of therapy to efavirenz-free regimens in experienced patients. Neurological and neuropsychiatric reactions are the manifestations most frequently experienced by efavirenz-treated patients and range from transitory effects, such as nightmares, dizziness, insomnia, nervousness and lack of conc…
Reduction of nevirapine-driven HIV mutations by carbamazepine is modulated by CYP3A activity
2014
Item does not contain fulltext OBJECTIVES: The reduction in mother-to-child transmission of HIV-1 by single-dose nevirapine given at birth onset is achieved at the expense of de novo HIV-1 resistance mutations. In the VITA1 study, single-dose carbamazepine accelerated nevirapine elimination, but the accompanying trend towards fewer de novo HIV-1 mutations was statistically non-significant. METHODS: We investigated if the effect of carbamazepine was confounded by the individual variability in nevirapine metabolism and transport. RESULTS: Nine of 34 (26%) single-dose nevirapine-treated women had one or more nevirapine-associated resistance mutations, compared with 3 of 34 (9%) in the single-d…
Inducing properties of rifampicin and rifabutin for selected enzyme activities of the cytochrome P-450 and UDP-glucuronosyltransferase superfamilies …
1996
Important species differences have been reported concerning the induction properties of rifampicin towards enzymes of the P-450 superfamily. Mice, rabbits and humans are far more responsive than rats and guinea pigs. In the present study a strong induction of cytochrome P-450 3A-dependent enzyme activities was observed in female rat liver microsomes after high dose treatment (> or = 250 mg/kg/day for 9 days) with rifampicin, resulting in an up to 30-fold enhanced hydroxylation rate of testosterone in the 2 beta-, 6 beta- and 15 beta-position in vitro. Other cytochrome P-450 isozyme-selective reactions were not, or only marginally, affected. A steep increase in cytochrome P-450 3A activity o…
Ingestion of plastic and non-plastic microfibers by farmed gilthead sea bream (Sparus aurata) and common carp (Cyprinus carpio) at different life sta…
2021
Environmental pollution by plastic particles is of major global concern, as a potential threat to aquatic organisms and ecosystems. The accumulation of microplastics in freshwater and marine environments has strong ecological implications due to their long persistence, potential toxicity, and ability to adsorb other pollutants, acting as vectors of pathogens. Nevertheless, while the number of studies on the presence of microplastics in the wild fish increased, less attention has been paid to the farmed fish species. Here, we investigated the occurrence of microparticles in the digestive tracts of Sparus aurata and Cyprinus carpio at different life stages and reared by an intensive and semi-…
Inhibitory effects and oxidation of 6-methylcoumarin, 7-methylcoumarin and 7-formylcoumarin via human CYP2A6 and its mouse and pig orthologous enzymes
2015
1. Information about the metabolism of compounds is essential in drug discovery and development, risk assessment of chemicals and further development of predictive methods. 2. In vitro and in silico methods were applied to evaluate the metabolic and inhibitory properties of 6-methylcoumarin, 7-methylcoumarin and 7-formylcoumarin with human CYP2A6, mouse CYP2A5 and pig CYP2A19. 3. 6-Methylcoumarin was oxidized to fluorescent 7-hydroxy-6-methylcoumarin by CYP2A6 (Km: 0.64-0.91 µM; Vmax: 0.81-0.89 min(-1)) and by CYP2A5 and CYP2A19. The reaction was almost completely inhibited at 10 µM 7-methylcoumarin in liver microsomes of human and mouse, but in pig only 40% inhibition was obtained with the…
Can multiscale simulations unravel the function of metallo-enzymes to improve knowledge-based drug discovery?
2019
Metallo-enzymes are a large class of biomolecules promoting specialized chemical reactions. Quantum-classical quantum mechanics/molecular mechanics molecular dynamics, describing the metal site at quantum mechanics level, while accounting for the rest of system at molecular mechanics level, has an accessible time-scale limited by its computational cost. Hence, it must be integrated with classical molecular dynamics and enhanced sampling simulations to disentangle the functions of metallo-enzymes. In this review, we provide an overview of these computational methods and their capabilities. In particular, we will focus on some systems such as CYP19A1 a Fe-dependent enzyme involved in estroge…
Development of new Coumarin-based profluorescent substrates for human cytochrome P450 enzymes
2018
Cytochrome P450 (CYP) enzymes constitute an essential xenobiotic metabolizing system that regulates the elimination of lipophilic compounds from the body. Convenient and affordable assays for CYP enzymes are important for assessing these metabolic pathways.In this study, 10 novel profluorescent coumarin derivatives with various substitutions at carbons 3, 6 and 7 were developed. Molecular modeling indicated that 3-phenylcoumarin offers an excellent scaffold for the development of selective substrate compounds for various human CYP forms, as they could be metabolized to fluorescent 7-hydroxycoumarin derivatives. Oxidation of profluorescent coumarin derivatives to fluorescent metabolites by 1…