Abstract：
:Cultured chick hepatocytes were used to investigate the hepatotoxicity of methotrexate alone and in combination with paracetamol. Treatment with methotrexate alone at concentrations as high as 1 mg/ml resulted in no toxicity in cultured chick hepatocytes, as indicated by no detachment of cells and no effect on protein synthesis or on release of the intracellular enzyme lactate dehydrogenase. However, treatment with methotrexate alone resulted in a 30% decrease in reduced glutathione levels. Combined treatment with methotrexate and paracetamol was toxic, but only in cells preinduced for cytochrome P450 1A by treatment with beta-naphthoflavone. Under these conditions, methotrexate lowered the threshold concentration of paracetamol at which toxicity was observed. This methotrexate-mediated increase in paracetamol toxicity was associated with decreased formation of the glucuronide, sulfate and thiol metabolites of paracetamol and with increased covalent binding of radiolabeled paracetamol to macromolecules. In cells pretreated with beta-naphthoflavone, additional treatment with either methotrexate or buthionine sulfoximine, an inhibitor of glutathione synthesis, together with paracetamol, was associated with decreased restoration of glutathione levels. These results suggest that methotrexate increased paracetamol toxicity by decreasing the amount of glutathione available for conjugation with reactive metabolites of paracetamol.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Lindenthal J,Sinclair JF,Howell S,Cargill I,Sinclair PR,Taylor Tdoi
10.1016/0926-6917(93)90063-vsubject
Has Abstractpub_date
1993-04-01 00:00:00pages
289-98issue
5-6eissn
0014-2999issn
1879-0712journal_volume
228pub_type
杂志文章abstract：:The inhibitory effect of forskolin-stimulated 3',5'-cyclic monophosphate (c-AMP) synthesis in isolated rat adipocytes has been measured for eight typical adenosine receptor agonists. The percent inhibition was evaluated using concentrations of each compound corresponding to 100 times their Ki, inhibitory binding const...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90224-0
更新日期：1994-03-15 00:00:00
abstract：:The anti-inflammatory activity of avarol and avarone, sesquiterpenoid derivatives from the Mediterranean sponge Dysidea avara, was investigated. Both compounds potently inhibited paw oedema induced by carrageenan (approximated ED50 = 9.2 and 4.6 mg/kg, p.o., respectively) as well as ear oedema induced by 12-O-tetradec...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90759-5
更新日期：1994-02-21 00:00:00
abstract：:Learning and memory are essential requirements for every living organism in order to cope with environmental demands, which enables it to adapt to changes in the conditions of life. Research on the effects of hormones on memory has focused on hormones such as adrenocorticotropic hormone (ACTH), glucocorticoids, vasopr...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(00)00556-2
更新日期：2000-09-29 00:00:00
abstract：:Proliferation and migration of vascular smooth muscle cells (VSMCs) play crucial roles in the development of vascular restenosis. Our previous study showed that CCN4, namely Wnt1 inducible signaling pathway protein 1 (WISP1), significantly promotes proliferation and migration of rat VSMCs, but its mechanism remains un...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.06.027
更新日期：2016-10-05 00:00:00
abstract：:The functional role of P2X7 receptor (P2X7R) inhibition in cancer-induced bone pain has been highly contradictory. Whereas knockout studies have suggested pro-nociceptive effects, pharmacological studies suggest anti-nociceptive or no effect. The discrepancy is likely linked to the highly polymorphic nature of the P2X...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.12.032
更新日期：2019-02-15 00:00:00
abstract：:The receptor for gonadotropin-releasing hormone (GnRH) belongs to the G-protein-coupled receptors, and its stimulation activates extracellular signal-regulated protein kinase (ERK). In the present study, we first examined the actions of GnRH on the ErbB family using two types of cultured gonadotroph cells. As reported...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.02.006
更新日期：2017-03-15 00:00:00
abstract：:Ischemia/reperfusion injury ends up in the cascade of excitotoxic stimulation of superoxide and nitric oxide formation leading to the generation of highly reactive products, including peroxinitrite and hydroxyl radical, which are capable of damaging lipids, proteins and DNA. Several polyphenolic compounds scavenge the...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.09.038
更新日期：2010-01-25 00:00:00
abstract：:[Thi5,8,D-Phe7]bradykinin caused hind-paw edema and degranulation of isolated peritoneal mast cells in a dose-dependent manner. Pretreatment with diphenhydramine/methysergide or compound 48/80 completely suppressed the edematous response caused by [Thi5,8,D-Phe7]bradykinin, whereas bradykinin-induced hind-paw swelling...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90836-4
更新日期：1989-02-28 00:00:00
abstract：:The interaction of the delta-opiate agonist [D-Ala2,D]Leu5]enkephalin (DADL) with the mu-opiate ligands dihydromorphine (DHM) and naloxone and the kappa-opiate ligand ethylketocyclazocine (EK) was studied in rat diencephalic membranes which contain mainly mu-opiate binding sites. Saturation binding experiments perform...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90145-5
更新日期：1982-02-05 00:00:00
abstract：:The leukotrienes are potent inflammatory mediators, which may have a role in inflammatory diseases such as allergic rhinitis, inflammatory bowl disease and asthma. Zafirlukast, a cysteinyl leukotriene receptor antagonist, is claimed to be effective in asthma. However, it is not known whether these leukotrienes are inv...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01083-4
更新日期：2001-06-29 00:00:00
abstract：:Systemic administration of the NMDA receptor antagonist phencyclidine (PCP; 4 mg/kg) produced a profound reduction in prepulse inhibition of the acoustic startle response in rats. Pre-treatment with the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) blocked (0.5 mg/kg) or attenuated (0.1 and 0.2...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00088-6
更新日期：1999-03-26 00:00:00
abstract：:Rat aortic smooth muscle rings without endothelial cells were subjected to alpha 1-adrenoceptor stimulation. We measured the contractile state of the smooth muscle cells and the formation of inositol phosphates (InsPs) on receptor stimulation. Using different extracellular calcium-containing solutions (2.5 mM, 0.1 mM ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0922-4106(05)80034-3
更新日期：1991-05-25 00:00:00
abstract：:Sprague-Dawley rats received oral doses of enalapril maleate (5 mg/kg), a potent, nonsulfhydryl, angiotensin converting enzyme inhibitor, or saline. Sixty min later, morphine sulfate, 5 mg/kg, or saline was injected subcutaneously. Response to a thermal stimulus was monitored before and up to 5 h ter morphine injectio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90607-1
更新日期：1984-02-17 00:00:00
abstract：:The inhibitory effects of the new bradykinin antagonist HOE 140 (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg) on depressor responses to exogenous bradykinin were investigated in conscious rats and compared with those of the bradykinin antagonist B4146 (D-Arg-Hyp-Pro-Gly-Thi-Ser-D-Pro-Thi-Arg). HOE 140 showed a 250-700...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90684-i
更新日期：1991-07-23 00:00:00
abstract：:Bone marrow stem cells are able to differentiate into nervous and endothelial cells. In our study, we found that administration of a bone marrow-stimulating factor (granulocyte colony-stimulating factor; G-CSF 50 microg/kg) decrease the brain infarct volume and enhance survival rate in a model of cerebral ischemia. Ta...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02785-1
更新日期：2003-01-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02360-9
更新日期：2002-10-18 00:00:00
abstract：:Results demonstrate for the first time that ethanol exerts two different effects on the lipid order of chick-liver mitochondria and microsomes: a fluidizing effect both in the core and at the surface of the membrane, which depends on its physical presence, and a rigidization of the surface of these membranes which occ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)90025-x
更新日期：1995-03-16 00:00:00
abstract：:Nerisopam, an anxiolytic and antipsychotic homophthalazine induces rapid, intense expression of Fos-like immunoreactivity in the rostral, dorsomedial and lateral parts of the striatum in the rat. Fos-positive cells also occurred in the globus pallidus, the olfactory tubercle and in the accumbens nucleus (in the cone a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01008-x
更新日期：1997-07-16 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90135-8
更新日期：1983-09-30 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00129-6
更新日期：1999-04-16 00:00:00
abstract：:Cats, sedated and paralyzed, showed a significant increase in body temperature after intravenous injection of morphine while animals with additional spinal blockade (C3) from injection of 2% lidocaine solution, did not. The results suggest that motor activity is not necessary for morphine-induced hyperthermia in the c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90113-9
更新日期：1978-06-01 00:00:00
abstract：:Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombotic activity of this drug. The present study shows that different heparin preparations (50 nM) completely prevent human platelet aggregation, se...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90437-9
更新日期：1992-06-17 00:00:00
abstract：:Induction of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, withaferin A inhibited LPS-induced expre...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.09.017
更新日期：2008-12-03 00:00:00
abstract：:Existing antimuscarinic drugs for overactive bladder have high affinity for M(3)/M(1) muscarinic receptors and consequently produce M(3)/M(1)-mediated adverse effects including dry mouth, constipation, mydriasis and somnolence. TD-6301 is a M(2/4) muscarinic receptor-selective antagonist developed for the treatment of...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.12.043
更新日期：2009-03-01 00:00:00
abstract：:We examined whether estrogen negatively modulates cannabinoid-induced regulation of food intake, core body temperature and neurotransmission at proopiomelanocortin (POMC) synapses. Food intake was evaluated in ovariectomized female guinea pigs abdominally implanted with thermal DataLoggers and treated s.c. with the ca...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.09.001
更新日期：2009-11-10 00:00:00
abstract：:Vancomycin (VCM) is a first-line antibiotic for serious infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is one of the most complaint in VCM therapy. We previously reported that VCM induced apoptosis in a porcine proximal tubular epithelial cell line (LLC-PK1), in which mitocho...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.02.025
更新日期：2017-04-05 00:00:00
abstract：:In the present study, we investigated the vasculoprotective effect of sigma-1 receptor stimulation with fluvoxamine on pressure overload hypertrophy-induced vascular injury in the thoracic aorta and defined mechanisms underlying that activity. Wistar rats underwent bilateral ovariectomy, and two weeks later were furth...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.10.055
更新日期：2011-01-15 00:00:00
abstract：:Because both long-term adrenoceptor agonist administration and antidepressant treatment in animals down-regulate CNS beta-adrenoceptors and attenuate brain adenylate cyclase activity, beta-adrenoceptor agonists may also possess antidepressant properties. We compared the effects of the centrally acting beta-adrenocepto...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90158-0
更新日期：1987-02-10 00:00:00
abstract：:Chronic restraint stress (CRS) is known to cause metabolic and neurological complications in a number of ways. Prolonged exposure to stress evident by increased corticosterone level led to impaired altered insulin signaling and oxidative stress in mice, in the present study. Impaired insulin signaling or insulin resis...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.07.056
更新日期：2018-09-15 00:00:00
abstract：:A series of 26 drugs was tested for in vitro binding to opiate receptors in the presence and absence of 0.1 M NaCl. The results were correlated with assays for in vivo pharmacological potency. Highly significant correlation was found between binding in the presence and absence of sodium ions and analgesic potency. For...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90334-x
更新日期：1977-12-01 00:00:00
