Search results for "polycyclic compounds"
showing 10 items of 373 documents
Phenytoin-induced glutathione depletion in rat peripheral nerve
1995
Abstract Administration of high doses (150–250 mg/kg body weight) of phenytoin (DPH) promote a 40% decrease in glutathione (GSH) content of rat sciatic nerve. This DPH-induced GSH depletion is accompanied with an electrophysiological impairment of peripheral neuromuscular function. H7 (20 mg/kg body weight IP, 30 min prior to DPH), a protein kinase C inhibitor, was able to prevent the DPH-induced GSH depletion only at the lower DPH dose used. This same inhibitor completely prevented the electrophysiological impairment at the lower DPH dose, and only partially at the higher DPH dose used. These results confirm the hypothesis of a DPH-dependent activation of PKC (that might be triggered by, o…
Inactivation of electrophilic metabolites by glutathione S-transferases and limitation of the system due to subcellular localization
1977
Benzo(a)pyrene was activated to metabolites mutagenic for Salmonella typhimurium TA 98 by liver microsomes from control and phenobarbital treated mice. Under these conditions benzo(a)pyrene 4,5-oxide accounts for most of the mutagenicity. We have therefore investigated (1) the conjugation of benzo(a)pyrene 4,5-oxide with glutathione and (2) the effect of glutathione on the mutagenicity of benzo(a)pyrene.
Effects of the flavonol quercetin on the bioavailability of simvastatin in pigs
2009
The influence of the dietary flavonol quercetin on the pharmacokinetics of the HMG-CoA reductase inhibitor simvastatin was investigated in pigs. Simvastatin (0.25mg/kg body weight) was orally administered to six pigs either without or with quercetin (10mg/kg). In addition, simvastatin was administered to three pigs that had received a diet supplemented with the flavonol over a period of 1 week. Daily quercetin intake was 10mg/kg in these animals. Co-ingestion of quercetin with the statin did not alter area under the concentration time curve (AUC(0-->infinity)), time to achieve maximum plasma concentration (t(max)) or half-life (t(1/2)) of simvastatin. However, there was a trend towards a re…
Bisdihydrodiols, rather than dihydrodiol oxides, are the principal microsomal metabolites of tumorigenic trans-3,4-dihydroxy-3,4-dihydrodibenz[a,h]an…
1994
Several studies on metabolism and biological activity of tumorigenic dibenz[a,h]anthracene (DBA) and its derivatives have led to the conclusion that the M-region dihydrodiol, trans-3,4-dihydroxy-3,4-dihydro-DBA (DBA-3,4-dihydrodiol), is the precursor of the ultimate mutagenic and tumorigenic metabolite of DBA with the presumed structure of a bay-region dihydrodiol oxide. Incubations of DBA-3,4-dihydrodiol (50 microM) with the microsomal hepatic fraction of Sprague-Dawley rats pretreated with Aroclor 1254 yielded more than 13 metabolites upon separation by HPLC. anti-3,4-Dihydroxy-1,2-epoxy-1,2,3,4-tetrahydro-DBA [0.27 nmol/(nmol of P450.15 min)] could be identified for the first time by UV …
Biosynthesis and transformation of 20α 21-dihydroxycholesterol by rat adrenal preparations
1979
Abstract The biosynthesis of [ 3 H]-20α, 21 dihydroxycholestderol from [ 3 H]-20α-hydroxycholesterol and its transformation to [ 3 H]-21-hydroxypregnenolone by rat adrenal preparations has been demonstrated. 20α-Hydroxycholesterol was transformed to 20α, 21-dihydroxycholesterol by microsomal preparations in the presence of NADPH and 20α-21-dihydroxycholesterol was metabolized to 21-hydroxypregnenolone by mitochondrial preparations in the presence of a NADPH-generating-system. Comparison of the Michaelis-Menten-Kinetics of the steps “20α, 21-dihydroxycholesterol → 21-hydroxycholesterol” and “20α-hydroxycholesterol → pregnenolone” revealed that both compounds behaved as analogue substrates of…
Effects of dopamine antagonists with different receptor blockade profiles on morphine-induced place preference in male mice.
2001
The effects of dopamine (DA) antagonists with different selectivity for the DA receptors (SCH 23390, 0.5, 0.25, 0.125 mg/kg; haloperidol, 0.2, 0.1 mg/kg; raclopride, 1.2, 0.6, 0.3 mg/kg; risperidone, 0.4, 0.2, 0.1 mg/kg; U-99194A maleate, 40, 20 mg/kg; clozapine, 2.5, 1.25, 0.625 mg/kg) on the acquisition of place conditioning and morphine-induced conditioned place preference (CPP) were explored in male mice. Morphine (40 mg/kg) produced CPP while SCH 23390, haloperidol and clozapine (highest dose) and risperidone (lowest dose) produced conditioned place aversion (CPA). Raclopride and U-99194A maleate did not produce CPP or CPA. Morphine-induced CPP was reversed by the administration of SCH…
Protein gene product (PGP) 9.5 immunoreactivity in nerve fibres and pinealocytes of guinea-pig pineal gland: interrelationship with tyrosine- hydroxy…
1993
This light-microscopic (LM) immunohistochemical study has evaluated the presence and distribution of the pan-neural and neuroendocrine marker protein gene product (PGP) 9.5 in pinealocytes and nerve fibres of guinea-pig pineal gland. The pattern of PGP 9.5-immunoreactive (ir) nerve fibres has been compared with that of fibres staining for tyrosine hydroxylase (TH) or neuropeptide Y (NPY). The vast majority of pinealocytes stained for PGP 9.5, although with variable intensity. PGP 9.5 immunoreactivity was localized in pinealocytic cell bodies and processes. Double-immunofluorescence revealed that PGP 9.5 immunoreactivity was absent from glial cells identified with a monoclonal antibody again…
Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice
2015
Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran-iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran-iron (15mg/kg) for 3weeks (D0-D20) and then (D21) a single su…
Oxytocin Regulates Neurosteroid Modulation of GABAAReceptors in Supraoptic Nucleus around Parturition
2003
In this study, we investigate how neurosteroid sensitivity of GABAAreceptors (GABAARs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABAARs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABAARs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABAARs from a neurosteroid-sensitive mode toward a …
Retroauricular skin: a flaps bank for ear reconstruction.
2006
Retroauricular skin: a flaps bank for ear reconstruction. Cordova A, D'Arpa S, Pirrello R, Giambona C, Moschella F. Source Cattedra di Chirurgia Plastica e Ricostruttiva, Dipartimento di Discipline Chirurgiche ed Oncologiche, Università degli Studi di Palermo, Via del Vespro 129, 90127 - Palermo, Italy. adriana.cordova@excite.com Abstract BACKGROUND: The retroauricular skin has always been given much attention by the reconstructive surgeon for ear and face reconstruction because it is richly vascularised, as many anatomical investigations show, it is hidden behind the ear, its skin is very similar to that of ear and face. All these reasons make it an ideal donor site for ear reconstruction.…