Abstract:
:Chlorpyrifos (CPF) is a pesticide that causes tens of thousands of deaths per year worldwide. Chlorpyrifos oxon (CPO) is the active metabolite of CPF that inhibits acetylcholinesterase. However, this presumed metabolite has escaped detection in human samples by conventional methods (HPLC, GC-MS, LC-MS) until now. A recently developed enzyme-based assay allowed the determination of CPO in the nanomolar range and was successfully employed to detect this metabolite. CPO and CPF were analysed in consecutive plasma samples of 74 patients with intentional CPF poisoning. A wide concentration range of CPO and CPF was observed and the ratio of CPO/CPF varied considerably between individuals and over time. The ratio increased during the course of poisoning from a mean of 0.005 in the first few hours after ingestion up to an apparent steady-state mean of 0.03 between 30 and 72h. There was a hundred-fold variation in the ratio between samples and the interquartile range (between individuals) indicated over half the samples had a 5-fold or greater variation from the mean. The ratio was independent of the CPF concentration and the pralidoxime regimen. CPO was present in sufficient quantities to explain any observed acetylcholinesterase inhibitory activity. The effectiveness of pralidoxime in reactivating the inhibited acetylcholinesterase is strongly dependent on the CPO concentration. Differences in clinical outcomes and the response to antidotes in patients with acute poisoning may occur due to inter-individual variability in metabolism.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Eyer F,Roberts DM,Buckley NA,Eddleston M,Thiermann H,Worek F,Eyer Pdoi
10.1016/j.bcp.2009.05.004subject
Has Abstractpub_date
2009-09-01 00:00:00pages
531-7issue
5eissn
0006-2952issn
1873-2968pii
S0006-2952(09)00372-4journal_volume
78pub_type
杂志文章abstract::We report here studies on the regulation of the metabolism of adenosine 3',5'-monophosphate (cAMP) in established and primary cultures of rat pulmonary microvascular endothelial cells (RPMVEC). Inhibition by rolipram, a selective inhibitor of cAMP phosphodiesterase (PDE) of the PDE4 gene family, was required to achiev...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00914-5
更新日期:2002-02-15 00:00:00
abstract::The thiopurines have a wide array of effects on purine metabolism, but the primary mechanism of cytotoxicity for both 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) appears to be incorporation of drug into DNA following conversion to the thioguanylate form. In murine leukemic cell lines exposed to a range of thiopur...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90333-r
更新日期:1993-11-02 00:00:00
abstract::After partial hepatectomy (PHx), there are significant changes in the activity of a number of enzymes in the regenerating rat liver. Administration of low doses of recombinant human tumor necrosis factor-alpha (rHu-TNF) to normal rats induces similar changes in some of the enzymes but not in others. Because certain ob...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00265-2
更新日期:1995-10-12 00:00:00
abstract::Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90016-x
更新日期:1991-01-01 00:00:00
abstract::The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O2 level, which is essential for their viability. It is important that this critical transcription factor be tightly regulated in order for cells to respond to a wide range of O2 concentrations. HIF-1 re...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2004.04.022
更新日期:2004-09-15 00:00:00
abstract::Local anaesthetics and opioid drugs function synergistically to provide analgesia. In the present study, the nature of this synergy has been investigated using in vitro radioligand binding to determine whether the local anaesthetics bupivacaine and tetracaine modulate the binding of two kappa-opioid receptor ligands, ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00512-k
更新日期:1995-03-30 00:00:00
abstract::Perfluorodecanoic acid (PFDA) alters the circulating level of thyroid hormones, but the physiological significance of this change at the target tissue remains to be defined. To this end, the activities of thyroid-responsive hepatic enzymes were examined in adult male rats 1 week after treatment with a single dose of P...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90091-8
更新日期:1987-04-15 00:00:00
abstract::The pregnane X-receptor (PXR) is a promiscuous nuclear receptor primarily responsible for the induction of genes from the cytochrome P450 3A family. In this study, we used a previously described PXR/SRC tethered protein to establish two in vitro assays for identifying PXR ligands: automated ligand identification syste...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.12.003
更新日期:2011-03-01 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::Enzymatic N,O-acyltransfer of carcinogenic N-arylhydroxamic acids such as N-hydroxy-2-acetylaminofluorene (N-OH-AAF) results in the production of reactive electrophiles that can bond covalently with nucleophiles and also can cause inactivation of acyltransferase activity in a mechanism-based manner. Incubation of part...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90277-r
更新日期:1990-03-15 00:00:00
abstract::Two methods avoiding the widespread technique of collagenase perfusion have been employed to study the regulation of total cytochrome P450 content in rat hepatocyte culture. One technique required the perfusion of the liver with the chelating agent EDTA to dissociate the parenchymal cells prior to culture. Over a peri...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90283-o
更新日期:1992-01-22 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::Castanospermine (CS) is a potent but non-selective inhibitor of many glycohydrolases including the intestinal disaccharidases. Several CS-glucosides were synthesized to investigate the effect of an attached glucopyranosyl residue on the potency and selectivity of CS toward inhibition of intestinal disaccharidases. 8 a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90518-p
更新日期:1990-05-15 00:00:00
abstract::Orexins are neuropeptides implicated in several physiological functions. Accumulating findings suggest a relationship between orexin and sepsis. A recent study demonstrated that orexin acts centrally to improve conditions in sepsis. The present study aims to clarify the precise mechanisms by which central orexin could...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114262
更新日期:2020-12-01 00:00:00
abstract::The sulfated glycolipid PG545 shows promising antitumor activity in various cancers. This study was conducted to explore the effects and the mechanism of PG545 action in endometrial cancer (EC). PG545 exhibited strong synergy as assessed by the Chou-Talalay-Method in vitro when combined with cisplatin, or paclitaxel i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114003
更新日期:2020-08-01 00:00:00
abstract::Treatment of normolipidemic rats by alkylthiopropionic acid (CETTD), resulted in a dose- and time-dependent increase in total dihydroxyacetone phosphate acyltransferase (DHAPAT) activity, in extent comparable to that of 3-thiadicarboxylic acid (BCMTD) and alkylthioacetic acid (CMTTD). Thus, in CETTD- and CMTTD-treated...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90230-i
更新日期:1990-11-01 00:00:00
abstract::Relatively low concentrations of ascorbic acid inhibited the binding of the alpha-1 adrenergic antagonist [125I]HEAT [DL-[beta(3-iodo-4-hydroxyphenyl)-ethyl-aminomethyl]-tetralone) in rat submandibular gland and rat aorta. However, no inhibition was observed with this ligand in several other tissues, nor with several ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90353-9
更新日期:1986-02-15 00:00:00
abstract::Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance. We therefore tested metformin alone and in combination with crizotinib in vivo, by...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114345
更新日期:2021-01-01 00:00:00
abstract::The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.10.007
更新日期:2010-03-01 00:00:00
abstract::Protocatechuic acid (PA), a structurally typical phenolic acid in danshen, shows anti-angina efficacy. But until now, besides scavenging of oxygen free radicals, the understanding of its anti-angina mechanism has been limited. In our study, based on a novel metabolic route of PA identified in rat heart and its influen...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.11.029
更新日期:2009-03-15 00:00:00
abstract::The inhibition of rat liver monoamine oxidase by a number of N-propargyl and alpha-methyl amine derivatives has been examined. The results indicate that alpha-methyl-substituted primary and secondary amine derivatives tend to show selectivity as reversible inhibitors towards the A-form of the enzyme. The structural fe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90012-0
更新日期:1982-04-01 00:00:00
abstract::The in vitro and in vivo effects of fluoxetine (and its active metabolite norfluoxetine) on mitochondrial respiration and F0F1-ATPase were studied, respectively, in mitochondria and submitochondrial particles isolated from rat liver. Fluoxetine in vitro inhibited state 3 mitochondrial respiration for alpha-ketoglutara...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90283-6
更新日期:1994-08-03 00:00:00
abstract::The protein tyrosine kinase (PTK) inhibitor genistein has been demonstrated to inhibit platelet-activating factor-stimulated prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-primed P388D1 macrophage-like cells (Glaser et al., J Biol Chem 265: 8658-8664, 1990). Therefore, the role of PTK in eicosanoid bio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90147-o
更新日期:1993-02-09 00:00:00
abstract::Pyruvate is an important metabolic intermediate, and also is an effective scavenger of hydrogen peroxide and other reactive oxygen species (ROS). Pharmacological administration of pyruvate has been shown to improve organ function in animal models of oxidant-mediated cellular injury. However, pyruvate is relatively uns...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2010.03.007
更新日期:2010-07-15 00:00:00
abstract::Glutathione (GSH) contributes to the detoxification of anticancer drugs through the operation of specific glutathione S-transferases (GST) and innate, or acquired, overexpression of this enzyme family has been frequently observed in tumor cell lines. In the GMA32 line of Chinese hamster fibroblasts, we showed that GSH...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)00452-r
更新日期:1995-01-31 00:00:00
abstract::Using a continuous perfusion system, synaptosomes prepared from rat brain released [3H]norepinephrine in a Ca2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10(-7) M), a sodium channel blocker, inhibited 48% of this pulsed release, and D595 (10(-5) M), a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90460-7
更新日期:1989-07-15 00:00:00
abstract::We have investigated whether or not the cellular content of reactive platinum, aside from total cellular and DNA-bound platinum, is a measure of the growth inhibitory potential of a given platinum complex. Human MCF-7 breast cancer cells, after treatment with cisplatin [cis-diamminedichloroplatinum(II)] and several 1,...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00106-2
更新日期:1996-07-12 00:00:00
abstract::The effect of the anti-tumor, anti-glutamine drug acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, was determined on the activity of the rate-limiting enzyme of de novo pyrimidine biosynthesis, carbamoyl-phosphate synthetase II (glutamine-hydrolyzing) (EC 6.3.5.5), in human colon carci...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90106-6
更新日期:1985-01-01 00:00:00
abstract::Andrographolide, a novel nuclear factor-κB (NF-κB) inhibitor, is isolated from leaves of Andrographis paniculata. Platelet activation is relevant to a variety of coronary heart diseases. Our recent studies revealed that andrographolide possesses potent antiplatelet activity by activating the endothelial nitric oxide s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.06.030
更新日期:2012-10-01 00:00:00
abstract::Uptake of two ellipticine derivatives, 2-N-methyl-ellipticinium (NME) and 2-N-methyl-9-hydroxy-ellipticinium, by sensitive and resistant Chinese hamster lung cells was studied. The results show that uptake and retention of these molecules by both types of cells were identical, thus indicating that the resistance to el...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90622-6
更新日期:1983-03-15 00:00:00