Abstract:
:The non-sedating anti-histamine, loratadine [ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin- 11-ylidene-1-piperidinecarboxylate], was administered orally in the diet to mature male rats at dosages of 4, 10 and 25 mg/kg/day for 2 weeks. The effects of these treatments on liver microsomal cytochrome P450 were evaluated by immunochemical and biochemical techniques, and were compared with the effects of treating rats with three different inducers of cytochrome P450, namely phenobarbital, 3-methylcholanthrene and dexamethasone. Treatment of rats with loratadine caused a dose-dependent increase in the levels of P450 2B1 and 2B2, the major phenobarbital-inducible P450 enzymes, as determined by Western immunoblotting. At the highest dosage tested, loratadine was less effective than phenobarbital as an inducer of 2B1 and 2B2, although the induction of these proteins could be detected immunochemically even at the lowest dosage of loratadine tested. Consistent with these observations, treatment of rats with loratadine caused a dose-dependent increase in the rate of two reactions that are catalyzed predominantly by 2B1/2, namely testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation. At the highest dosage tested, loratadine caused a 7.3- and 8.5-fold increase in the rate of testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation, respectively, compared with a 22- and 45-fold increase caused by phenobarbital treatment. Treatment of rats with loratadine caused a 1.4- to 2.0-fold increase in the 2 beta-, 6 beta- and 15 beta-hydroxylation of testosterone, which was associated with a similar increase in the levels of immunoreactive P450 3A1 and/or 3A2. As an inducer of P450 3A1/2, loratadine was slightly less effective than phenobarbital, and was considerably less effective than dexamethasone, which caused a 10- to 33-fold increase in testosterone 2 beta-, 6 beta- and 15 beta-hydroxylase activity. At the dosages tested, loratadine did not increase the levels of P450 1A1, the major 3-methylcholanthrene-inducible P450 enzyme, as determined by Western immunoblotting. The rate of 7-ethoxyresorufin O-dealkylation, which is catalyzed predominantly by P450 1A1, increased 1.9-fold after loratidine treatment, but this increase was less than that caused by phenobarbital treatment (2.2-fold), and was considerably less than that caused by 3-methylcholanthrene treatment (33-fold). The effects of treating mature male mice with loratadine on liver microsomal cytochrome P450 resembled the effects observed in rats. These results indicate that loratadine is a phenobarbital-type inducer of liver microsomal cytochrome P450 in rats and mice.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Parkinson A,Clement RP,Casciano CN,Cayen MNdoi
10.1016/0006-2952(92)90176-jsubject
Has Abstractpub_date
1992-05-28 00:00:00pages
2169-80issue
10eissn
0006-2952issn
1873-2968pii
0006-2952(92)90176-Jjournal_volume
43pub_type
杂志文章abstract::The interaction of the vasodilator, hydralazine, with the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase has been investigated. A potent progressive inhibition of rabbit liver aldehyde oxidase, in the presence of substrate, by low concentrations of hydralazine (0.1-1 microM) was observed in vitro but n...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90280-1
更新日期:1985-12-15 00:00:00
abstract::During the molecular transduction of itch, the stimulation of pruriceptors on sensory fibers leads to the activation or sensitization of ion channels, which results in a consequent depolarization of the neurons. These ion channels mostly belong to the transient receptor potential (TRP) channels, which are involved in ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114310
更新日期:2021-01-01 00:00:00
abstract::Pioglitazone (PIO), a PPARγ agonist that improves glycemic control in type 2 diabetes through its insulin-sensitizing action, has been shown to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis afte...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.11.026
更新日期:2016-02-01 00:00:00
abstract::Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to antic...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.09.024
更新日期:2011-01-15 00:00:00
abstract::The biotransformation and the hepato- and nephrotoxicity of the mercapturic acids (N-acetyl-1-cysteine S-conjugates) of three structurally related 2,2-difluoroethylenes were investigated in vivo in the rat. All mercapturic acids appeared to cause nephrotoxicity, without any measureable effect on the liver. The mercapt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90665-x
更新日期:1988-12-01 00:00:00
abstract::Our results indicate that sex hormones play an important role in the regulation of brain and hepatic GST protein during maturity. The conjugating factor GSH does not appear to be under the influence of sex hormones. These observations are of great significance in view of the possibility of continued exposure to neurot...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90312-4
更新日期:1982-12-01 00:00:00
abstract::To study the effect of sex hormones and alcohol on the hepatic activities of alcohol metabolizing enzymes, estradiol or testosterone were administered for 4 weeks to ovarectomized or sham operated adult female rats pair-fed nutritionally adequate liquid diets containing either alcohol (36% of total calories) or isocal...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90229-7
更新日期:1986-02-01 00:00:00
abstract::Within the tissue surrounding the necrotic lesion, following a cryogenic injury of the brain, there is a definite activation of phospholipase A2 (at 2 and 4 hr post lesion) that accounts, at least in part, for the phospholipid breakdown. There is also an activation of cholinephosphotransferase (at 2 hr post lesion) th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90022-0
更新日期:1987-11-01 00:00:00
abstract::The present study focused on the desensitization process of the H(2) receptor in U937 cells and the recovery of the cyclic AMP (cAMP) response. Treatment of U937 leukemic cells with the H(2) histamine receptor agonists (+/-)-N(1)-[3-(3, 4-difluorophenyl)-3-(pyridin-2-yl)propyl]-N(2)-[3-(1H-imidazol-4-yl)p ropyl]guanid...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00295-1
更新日期:2000-07-15 00:00:00
abstract::Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are local...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.06.030
更新日期:2013-09-15 00:00:00
abstract::The current obesity epidemic is a major worldwide health and economic burden. In the modern environment, an increase in the intake of high-fat and high-sugar foods plays a crucial role in the development of obesity by disrupting the mechanisms governing food intake and energy balance. Food intake and whole-body energy...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2018.07.008
更新日期:2018-09-01 00:00:00
abstract::The amino acid conjugation of the phenoxyherbicides 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T) by animals was examined at the level of the enzymes catalyzing the reactions. The phenoxyherbicides were not substrates for the bile acid conjugating system but were substrates for the mit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90528-9
更新日期:1986-01-15 00:00:00
abstract::Serotonin plays a critical role in the regulation of intestinal physiology. The serotonin transporter (SERT) expressed in the intestinal epithelium determines 5-HT availability and activity. The serotoninergic system and SERT activity have been described as being altered in chronic intestinal pathologies such as infla...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.06.006
更新日期:2009-11-01 00:00:00
abstract::2-Fluoroadenine (F-Ade) is a metabolite of 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) that may be involved in the development of toxic side effects from this anticancer drug. The liberation of F-Ade from F-ara-A has been examined in different biological systems. Extracts of Escherichia coli but not mammalian ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90207-3
更新日期:1987-09-15 00:00:00
abstract::Glutathione reductase (GR) one of the enzymes of the glutathione redox cycle, plays a salient role in maintaining appropriate cellular levels of reduced glutathione. The enzyme in human red blood cells is inhibited in vitro by the anticonvulsant drug valproic acid (VPA). The inhibition is dose-dependent, reversible, u...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90559-2
更新日期:1992-02-04 00:00:00
abstract::Multiple molecular forms of cyclic nucleotide phosphodiesterase have been characterized in various tissues and cells according to their substrate specificity, intracellular location, and calmodulin dependence. The purpose of this study was to evaluate the possible involvement of different molecular forms of phosphodie...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90304-4
更新日期:1990-08-15 00:00:00
abstract::Only very low levels of peroxidase activity were detected in castrated male hamster kidneys [1.0 +/- 0.8(S.E.) units/g protein], and chronic estrogen administration, either diethylstilbestrol (DES) or 17 beta-estradiol, for 1-5 months did not result in any appreciable increase in this activity. In contrast, hamster li...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90529-4
更新日期:1983-02-01 00:00:00
abstract::Ciprofibrate (CP), a peroxisome proliferator, has been shown to reduce rat liver endoplasmic reticulum (ER) Ca(2+)-ATPase activity both in vitro and in vivo. The ER Ca(2+)-ATPase is highly susceptible to thiol reactivity, and maintenance of maximal enzyme activity is critically dependent upon the integrity of these th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90021-n
更新日期:1993-05-25 00:00:00
abstract::The long-term effects of incubating freshly isolated, elicited guinea-pig peritoneal macrophages with the beta-adrenoceptor agonist isoprenaline and the selective inhibitor of phosphodiesterase (PDE) IV rolipram, on adenosine-3',5'-cyclic phosphate (cAMP)-specific PDE IV activity have been investigated. The level of c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02104-3
更新日期:1995-12-22 00:00:00
abstract::Phospho-tyrosol-indomethacin (PTI; MPI 621), a novel anti-cancer agent, is more potent and safer than conventional indomethacin. Here, we show that PTI was extensively metabolized in vitro and in vivo. PTI was rapidly hydrolyzed by carboxylesterases to generate indomethacin as its major metabolite in the liver microso...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.01.031
更新日期:2013-04-15 00:00:00
abstract::The possibility of NQ12 (2-chloro-3-[4-(ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone) as a novel antithrombotic agent and its mode of action were investigated. The effects of NQ12 on platelet aggregation in human platelet-rich plasma in vitro, in rats ex vivo, and on murine pulmonary thrombosis in vivo, as well as t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00411-1
更新日期:2000-10-01 00:00:00
abstract::Elevated glucose levels in diabetes mellitus is associated with increased oxidized low density lipoprotein (oxLDL). High glucose (HG) and oxLDL are key inducers of oxidative stress and inflammatory processes responsible for diabetic vascular disorders. Rosmarinic acid is a polyphenol with antioxidant, anti-inflammator...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114246
更新日期:2020-12-01 00:00:00
abstract::The calcium-ionophore A23187 causes a reversible increase of the hydrostatic pressure in the portal vein of perfused rat liver. Concomitantly, hepatic functions like the production of bile and the transhepatic movement of the bile acid taurocholate are diminished, mainly due to decreased uptake. These phenomena are pa...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90221-8
更新日期:1987-09-15 00:00:00
abstract::We have examined chromosome damage caused by a wide range of bleomycin (BLM) concentrations in Chinese hamster ovary (CHO-K1) cells reversibly porated by the bacterial cytotoxin streptolysin-O (SLO). Chromosome damage was measured using the micronucleus cytokinesis block technique (employing cytochalasin-B). Treatment...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90128-j
更新日期:1993-02-09 00:00:00
abstract::Dimebolin (Dimebon), is a non-selective antihistamine approved in Russia for the treatment of allergy. Recently, this drug has been shown to be neuroprotective in cellular models of Alzheimer's disease and Huntington's disease, and to preserve cognitive function when chronically administered to AF64A lesioned rats. In...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.06.021
更新日期:2009-10-15 00:00:00
abstract::Energy-dependent drug efflux is a major factor in cellular resistance of P388/R84 mouse leukemic cells to anthracyclines such as doxorubicin (DOX), and blocking of efflux increases sensitivity. However, efflux does not play a significant role in resistance to N-trifluoroacetyladriamycin-14-valerate (AD 32), a DOX anal...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90151-a
更新日期:1990-02-15 00:00:00
abstract::The diterpenes andrographolide (I), andrographiside (II) and neoandrographolide (III) isolated from Andrographis paniculata were investigated for their protective effects on hepatotoxicity induced in mice by carbon tetrachloride or tert-butylhydroperoxide (tBHP) intoxication. Pretreatment of mice with the diterpenes (...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90364-3
更新日期:1993-07-06 00:00:00
abstract::Treatment of red blood cells with the copper (II) ascorbate system causes increased lipid peroxidation, increased membrane microviscosity, and phospholipid translocation with a concurrent decrease in cytosolic catalase and glutathione peroxidase activities. All these changes are prevented if the cells are treated with...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00277-4
更新日期:2000-02-15 00:00:00
abstract::Despite tobacco being highly addictive, it is unclear if nicotine has significant affective properties. To address this, we studied taste reactions to gustatory stimuli, palatable sucrose and unpalatable quinine, which are believed to reflect ongoing affective state. Taste reactivity was assessed during chronic nicoti...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.06.017
更新日期:2009-10-01 00:00:00
abstract::The effect of oxidant stress produced by redox cycling of substituted 1,4-naphthoquinones on the activity of platelet (Na(+)-K+)ATPase and the active transport of serotonin (5-HT) was studied. 2-Methyl-1,4-naphthoquinone (menadione) produced a concentration-dependent (0-100 microM) and time-dependent (2-20 min) stimul...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90203-h
更新日期:1991-03-15 00:00:00