Abstract:
:Colchicine disposition involves both active biliary and renal excretion of parent drug, and at least in mammals a substantial fraction undergoes hepatic demethylation prior to excretion. We investigated the biotransformation of [3H]colchicine in a panel of microsomal preparations obtained from sixteen human liver samples. The production rate of the main metabolites of colchicine's 3-demethylcolchicine (3DMC) and 2-demethylcolchicine (2DMC), was linear in relation to incubation time, cytochrome (P450) content, and substrate concentration. Following the incubation of colchicine (5 nM) with microsomes in the presence of an NADPH-generating system for 60 min, 9.8% and 5.5% of the substrate were metabolized to 3DMC and 2DMC, respectively. The formation rate of colchicine metabolites exhibited a marked variation between the different microsomal preparations. The formation rates of both colchicine metabolites were correlated significantly with nifedipine oxidase activity, a marker of CYP3A4 activity (r = 0.96, P < 0.001), but not with the metabolic markers of CYP2A6, CYP2C19, CYP2C9, CYP2D6, and CYP2E1 activities. Chemical inhibition of CYP3A4 by preincubation with gestodene (40 microM) or troleandomycin (40 microM) reduced the formation of 3DMC and 2DMC by 70 and 80%, respectively, whereas quinidine, diethyldithiocarbamate, and sulfaphenazole had no inhibitory effect. Similarly, antibodies raised against CYP3A4 almost completely abolished colchicine demethylation and nifedipine oxidase activity, but preimmune IgG had no effect. In conclusion, colchicine was metabolized to 3DMC and 2DMC by human liver microsomes. The production of colchicine metabolites was mediated by CYP3A4, and its rate varied greatly between microsomal preparations obtained from different liver samples. The coadministration of colchicine with known inhibitors or substrates of CYP3A4 may inhibit colchicine metabolism, resulting in concentration-related toxicity.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Tateishi T,Soucek P,Caraco Y,Guengerich FP,Wood AJdoi
10.1016/s0006-2952(96)00693-4subject
Has Abstractpub_date
1997-01-10 00:00:00pages
111-6issue
1eissn
0006-2952issn
1873-2968pii
S0006295296006934journal_volume
53pub_type
杂志文章abstract::Reactive oxygen and nitrogen species are overproduced in the cardiovascular system in response to the exposure to doxorubicin, a cardiotoxic anticancer compound. Oxidant-induced cell injury involves the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and pharmacological inhibition of PARP has recen...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.11.023
更新日期:2005-03-01 00:00:00
abstract::Poly(ADP-ribosylation) consists in the conversion of β-NAD(+) into ADP-ribose, which is then bound to acceptor proteins and further used to form polymers of variable length and structure. The correct turnover of poly(ADP-ribose) is ensured by the concerted action of poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2010.04.022
更新日期:2010-12-15 00:00:00
abstract::A novel enzyme that converts dihydroxyphenylacetic acid (DOPAC) to dihydroxyphenylethanol (DOPET) was found to be present in the microdialysate of the rat brain. The enzyme, named DOPAC reductase, was inhibited by EDTA and stimulated by divalent cations like Zn2+, Mn2+, Co2+ and Cu2+. Its Km, pH optimum and temperatur...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02092-6
更新日期:1995-10-26 00:00:00
abstract::The human ether-a-go-go-related gene (hERG) encodes the rapidly activating, delayed rectifier potassium channel (IKr) important for cardiac repolarization. Dysfunction of the hERG channel can cause Long QT Syndrome (LQTS). A wide variety of structurally diverse therapeutic compounds reduce the hERG current by acute di...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.09.002
更新日期:2013-01-01 00:00:00
abstract::Female Wistar rats were treated with acetaminophen 3.0 g/kg BW and allyl alcohol 75 microliter/kg BW by gastric tube. Hepatic function, measured as galactose elimination capacity and prothrombin index, was reduced to about 0.40 times control value. Plasma alanine transferase activity was elevated more and earlier afte...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90750-6
更新日期:1985-03-15 00:00:00
abstract::The toxicity of the organophosphorus poison soman (pinacolylmethylphosphonofluoridate) is attributable to its irreversible inhibition of the enzyme acetylcholinesterase. In addition, soman binds irreversibly to a number of noncholinesterase tissue binding sites which appear to be its major means of in vivo detoxificat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90349-p
更新日期:1990-10-15 00:00:00
abstract::A voluminous number of evidence suggests that an increased consumption of fruit and vegetables is a relatively easy and practical strategy to reduce significantly the incidence of chronic diseases, such as cancer, cardiovascular diseases and other aging-related pathologies. This review will critically discuss the appl...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2007.02.014
更新日期:2007-08-15 00:00:00
abstract::The insulin receptor (IR) is composed of two alpha-chains that bind ligands and two beta-chains that possess an intracellular tyrosine kinase activity. The IR is expressed in cells as two isoforms containing or not exon 11 (IRB and IRA, respectively). Several mRNA studies have demonstrated that the two isoforms are co...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.07.027
更新日期:2008-10-01 00:00:00
abstract::When INH was administered orally or intraperitoneally to pregnant female mice, the concentrations of acetyl INH and acetyl hydrazines did not vary significantly in circulating blood and in amniotic fluid. However, the concentration of INH in the amniotic fluid was significantly higher than that observed in the serum. ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90484-7
更新日期:1983-02-15 00:00:00
abstract::In a series of colorectal cancer cell lines, both necrosis and apoptosis were induced upon exposure to oxaliplatin, and enhanced by co-administration of the Hsp90 inhibitor 17-AAG. We analyzed the effects of these interventions on the cell cycle, and found that oxaliplatin treatment caused G1 and G2 arrest in HCT116 c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.01.037
更新日期:2007-06-01 00:00:00
abstract::This investigation suggests that the oxazolidine derivative of propranolol is a prodrug which is hydrolysed stereoselectively to propranolol by hepatic post-mitochondrial supernatant. The (S)-form of the prodrug is more stable in the biological system than its (R)-form. ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90113-j
更新日期:1991-05-01 00:00:00
abstract::The study of binding is not an easy task especially because of the difficulty of interpreting the results in terms of binding on specific receptor sites. The problem is not new; what is new is the increasing amount of fanciful interpretation that such a technique has generated. The tendency to interpret anomalous or i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90436-2
更新日期:1984-03-15 00:00:00
abstract::Metabolic and cardiovascular disease patients have increased plasma levels of lipids and, specifically, of palmitate, which can be toxic for several tissues. Trimetazidine (TMZ), a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, its mech...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.07.022
更新日期:2014-10-01 00:00:00
abstract::Chemokines and their receptors play fundamental roles in many physiological and pathological processes such as leukocyte trafficking, inflammation, cancer and HIV-1 infection. Chemokine-receptor interactions are particularly intricate and therefore require precise orchestration. The flexible N-terminal domain of human...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2012.08.008
更新日期:2012-11-15 00:00:00
abstract::DUP 785 (NSC 368390; Brequinar sodium) is a new inhibitor of pyrimidine de novo biosynthesis with antitumor activity against several experimental tumors. DUP 785 inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, blocking the conversion of dihydroorotate to orotate. We examined the influence of exposure t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90636-3
更新日期:1988-09-01 00:00:00
abstract::Petrosaspongiolide M (PT) is a potent secretory phospholipase A(2) inhibitor and anti-inflammatory agent. This marine metabolite reduced the production of nitrite, prostaglandin E(2), and tumor necrosis factor-alpha in the mouse air pouch injected with zymosan. These effects were also observed in mouse peritoneal macr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01659-3
更新日期:2003-03-01 00:00:00
abstract::Heme oxygenase 1 (HO-1) is a stress protein and has been suggested to provide defense mechanisms against agents that may induce oxidative injury. Vitamin E (VE) is considered to function as an important cellular antioxidant. Rats were fed a VE-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then were intr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00302-x
更新日期:1997-11-15 00:00:00
abstract::The vasoactive urotensin-II (UII), a cyclic undecapeptide widely distributed in cardiovascular, renal and endocrine systems, specifically binds the UII receptor (UT receptor), a G protein-coupled receptor (GPCR). The involvement of this receptor in numerous pathophysiological conditions including atherosclerosis, hear...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.08.023
更新日期:2014-11-15 00:00:00
abstract::This study was designed to examine the relationship between the extent of Sandimmun (cyclosporin A, SIM) metabolism and SIM-induced hepatotoxicity both in vivo and in primary cultures of rat hepatocytes. Firstly, SIM (50 mg/kg p.o.) was administered daily to male Wistar rats for 10 days with or without co-administrati...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90024-f
更新日期:1990-01-15 00:00:00
abstract::Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated respon...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90284-4
更新日期:1993-03-24 00:00:00
abstract::Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based metabolomics was employed to decipher ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.05.001
更新日期:2014-07-15 00:00:00
abstract::The metabolism of alpha,alpha,beta,beta- tetradeutero -N,N -dimethyltryptamine ( D4DMT ) in rat brain in vivo as a function of time and dose was examined. Quantification of D4DMT and its respective deutero-metabolites was accomplished using gas chromatographic/mass spectrometric/selected ion monitoring/isotope dilutio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90404-0
更新日期:1984-05-01 00:00:00
abstract::Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme of the human immunodeficiency virus (HIV-1). Molecular modeling studies indicated that because of the asymmetric geometry of the non-nucleoside inhib...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.01.019
更新日期:2004-05-15 00:00:00
abstract::Resveratrol decreases basal and induced CYP1A1 mRNA/protein levels in both in vitro and in vivo models, and some studies suggest that resveratrol acts as an aryl hydrocarbon receptor (AhR) antagonist. Treatment of T47D or MCF-7 cells with 10 microM resveratrol inhibited induction of CYP1A1 mRNA and CYP1A1-dependent ac...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00763-8
更新日期:2001-10-15 00:00:00
abstract::The localization of the low-affinity adenosine binding protein adenotin-1 with respect to distribution in rat organs and subcellular compartments was investigated. Adenotin-1 was characterized by 5'-N-ethylcarboxamido[2,8-3H]adenosine ([3H]NECA) binding and Western blotting. Cytosolic as well as membrane fractions of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00483-8
更新日期:1998-02-15 00:00:00
abstract::The inhibitory effects of N-(4-hydroxyphenyl)retinamide (HPR) and its glucuronide derivative on the growth of MCF-7 human breast cancer cells in vitro were compared. The results indicate that the glucuronide had slightly greater potency and much less cytotoxicity than the free retinoid. At a concentration of 10(-6) M,...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90563-k
更新日期:1991-05-15 00:00:00
abstract::Allosteric regulation of [3H]N-methylscopolamine [( 3H]NMS) and [3H]quinuclidinyl benzilate [( 3H]QNB) dissociation from the m1-m5 muscarinic receptor subtypes was examined in transfected CHO-K1 cells. Half-times of dissociation of [3H]NMS from cell membranes (at 23 degrees) ranged from less than 5 min for the m2 subt...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90591-r
更新日期:1991-10-24 00:00:00
abstract::N-[(2'-Dimethylamino)ethyl]acridine-4-carboxamide (DACA) is a new anticancer agent currently undergoing clinical trials. The metabolism of DACA to acridone metabolites by aldehyde oxidase (AO) (EC 1.2.3.1) appears to play a major role in its elimination in human patients and rodents. The aim of this study was to compa...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00323-8
更新日期:2000-01-15 00:00:00
abstract::Macrophages are key inflammatory cells in chronic obstructive pulmonary disease (COPD). The pathophysiology of cigarette smoke-induced lung emphysema is complex but there is a clear role for reactive oxygen species (ROS, such as peroxynitrite), tumor necrosis factor (TNF-alpha) and interleukin (IL)-8. We investigated ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.10.001
更新日期:2010-03-01 00:00:00
abstract::The effects of injections of a synthetic adrenocorticotropin (ACTH 1-17, Synchrodyn) on the rate of DNA labeling in the metaphyseal bone of CD2F1 mice were tested on a chronopharmacological dosing schedule. Groups of mice that had been conditioned to a 12-hr light/12-hr dark schedule were injected at one of six differ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90494-0
更新日期:1985-04-15 00:00:00