1,721,219 research outputs found
Effect of the hypolipidemic drug bezafibrate on the hepatic mixed function oxidase system of the rat: heterogeneity monooxygenase responses
No full textAdministration of 100 mg/Kg of the hypolipidemic drug Bezafibrate for five consecutive days to the rat causes a marked liver enlargement and an alteration of the mixed function oxidase (MFO) system. Cytochrome P-450 levels are increased in liver microsomes from treated rats by 80%, NADPH-cytochrome c reductase activity by 45% and aminopyrine N-demethylase activity by 40%. On the contrary, other MFO activities (p-nitroanisole O-demethylase, hexobarbital oxidase, aniline hydroxylase and zoxazolamine hydroxylase) remain unchanged. The type of P-450 hemoprotein induced shows different spectroscopic properties in the binding of CO, Type II and Type RI ligands in respect to cytochrome P-450 of the controls. These results reveal differential alterations of the MFO system and the induction of one specific type of cytochrome P-450 hemoprotein
The inhibitory effect of pyrazinamide on microsomal monooxygenase activities is related to the binding to reduced cytochrome P-450
No full textThe antitubercular agent Pyrazinamide (PZA) binds to oxidized and reduced rat liver microsomal cytochrome P-450 with the binding characteristics typical of basic heterocyclic compounds. The PZA-cytochrome P-450(Fe2+) interaction, although characterized by rather weak affinity (Ks = 4 × 10-3M), has a PZA-cytochrome P-450(Fe2+) bond of considerable strenght and stability. PZA has an inhibitory effect on the aniline hydroxylase, p-nitroanisole O-demethylase and aminopyrine demethylase activities of rat liver microsomes. The PZA-cytochrome P-450(Fe2+) binding characteristics explain the observed inhibitory effect of the drug on the monooxygenase activities
[A rapid, specific and sensitive method for the identification of anthelmintic drug residues in milk and meat using mass spectrometry MS/MS]
No full textRecent advances in the assessment of the antioxidant capacity of pharmaceutical drugs : from in vitro to in vivo evidence
No full textIn this review, some well-established assays and more recent markers developed for the understanding of the biological activity of pharmaceutical drugs belonging to different pharmacological classes (nonsteroidal anti-inflammatory drugs, cardiovascular drugs, and central-nervous-system-acting drugs) are considered. The results of in vitro studies are reviewed and critically compared with those available from clinical trials, and their relevance for the elucidation of the mechanism of action of the drugs is discussed. Although from this examination a positive correlation between the in vitro and in vivo data seems to emerge, the small number of clinical trials available, their low number of patients enrolled, and sometimes the arbitrary or inappropriate choice of the biomarker(s) used highlight the need for (1) more standardized protocols to allow a reliable comparison of the results from different studies and (2) the development of new and more appropriate and specific biomarkers for the evaluation of oxidative stress before and after drug intervention
Loss of substrate binding capacity of the hepatic microsomal cytochrome P-450 in Fasciola hepatica infected rats: toxicological implications
No full textExperimental fascioliasis in the rat is responsible for a dramatic decrease in the drug-metabolizing ability of the hepatic monooxygenase system. The present investigation, through a spectroscopic study of hexobarbital interaction with microsomal cytochrome P-450 and in vitro and in vivo studies of hexobarbital metabolism in the rat, demonstrates that this decrease is due to an alteration in the structure of the hemoprotein (loss of substrate binding capacity of cytochrome P-450 followed by denaturation). These results might be responsible for a decreased safety margins for those flukicidal agents that are detoxified by the monooxygenase pathway, and might explain the accumulation problems frequently associated with chemotherapy of Fasciola hepatica
Un metodo rapido, specifico e sensibile di identificazione dei residui di farmaci antielmintici nel latte e carne mediante spettrometria di massa MS/MS
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Liver metabolism of the fasciolicide drug nitroxinil in rats experimentally infected with Fasciola hepatica
No full textThe urinary excretion of the main metabolites of nitroxinil was greatly reduced in experimentally infected rats
METABOLISM OF THE HYPOLIPIDEMIC AGENT TIADENOL IN MAN AND IN THE RAT
No full textThe metabolism of the hypolipidemic agent 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) has been studied in vivo in man and in the rat and in vitro in the rat. Following oral administration, in both species tiadenol was completely absorbed, extensively metabolized by the liver and more than 95% of the dose was eliminated in this form via kidneys within 48 h. Insignificant was the excretion of the unchanged drug in urine (approximately 1%) as well as that of its metabolites in the feces. 8 metabolites were isolated from human or rat urine and their structures were elucidated by means of electron impact, field desorption and positive and negative fast atom bombardment mass spectrometry. Both in man and in the rat the main metabolic pathway was the oxidation of the thioether sulfur, followed by oxidation or conjugation of the primary alcohol group(s). The urinary excretion of S-oxidized metabolites and sulfoxidized carboxylic metabolites accounted for 75% of the dose and that of S-oxidized conjugated metabolites for 20%. Rat in vitro studies showed that hepatic microsomal cytochrome P-450-dependent monooxygenase catalyzes the S-oxidative pathway, which governs the in vivo elimination of the drug in both species. Thus cytochrome P-450 is the key enzyme in the hepatic detoxification of tiadenol
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