Hepatic microsomal metabolism of the dichloroethanes.

Abstract:

:The binding of 1,1-dichloroethane (1,1-DCE) to the substrate binding site of hepatic microsomal cytochrome P-450, and the stimulation of hepatic microsomal CO-inhibitable NADPH oxidation by 1,1-DCE and 1,2-dichloroethane (1,2-DCE) were enhanced by induction with phenobarbital but not with beta-naphthoflavone. Incubation of the dichloroethanes with hepatic microsomes from phenobarbital-treated rats, NADPH-generating system and EDTA resulted in the conversion of 1,1-DCE to acetic acid and to a lesser extent to 2,2-dichloroethanol and probably also mono- and dichloroacetic acid and the conversion of 1,2-DCE to chloroacetaldehyde and to a lesser extent to chloroacetic acid and probably 2-chloroethanol. In addition, reaction mixtures constituted as described above resulted in slight but significant losses (ca. 13%) of hepatic microsomal cytochrome P-450. The omission of dichloroethane or the NADPH-generating system from incubation mixtures eliminated the above effects, and SKF-525A or CO diminished or eliminated the effects. Pathways for the metabolism of 1,1-DCE and 1,2-DCE are proposed.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

McCall SN,Jurgens P,Ivanetich KM

doi

10.1016/0006-2952(83)90545-2

subject

Has Abstract

pub_date

1983-01-15 00:00:00

pages

207-13

issue

2

eissn

0006-2952

issn

1873-2968

pii

0006-2952(83)90545-2

journal_volume

32

pub_type

杂志文章
  • Saturation mutagenesis at dihydrofolate reductase codons 22 and 31. A variety of amino acid substitutions conferring methotrexate resistance.

    abstract::Naturally occurring amino acid substitutions conferring resistance to methotrexate (MTX) have been reported previously at codon positions 22 (leu-->arg, phe) and 31 (phe-->ser, trp) of mammalian dihydrofolate reductases (DHFR). To explore the character of other substitutions, a polymerase chain reaction (PCR)-assisted...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90393-x

    authors: Morris JA,McIvor RS

    更新日期:1994-03-29 00:00:00

  • Inhibition of phosphate transport in rat heart mitochondria by 3'-azido-3'-deoxythymidine due to stimulation of superoxide anion mitochondrial production.

    abstract::In order to gain some insight into the mechanism by which 3'-azido-3'-deoxythymidine (AZT) damages mitochondria, we investigated whether externally added AZT can stimulate reactive oxygen species (ROS) production by rat heart mitochondria (RHM). An increase in superoxide anion ((O(2)(.-)) production was measured in RH...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(02)01065-1

    authors: Valenti D,Atlante A,Barile M,Passarella S

    更新日期:2002-07-15 00:00:00

  • Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.

    abstract::Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (ago...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.bcp.2011.05.001

    authors: Williams DK,Wang J,Papke RL

    更新日期:2011-10-15 00:00:00

  • Hepatic alcohol metabolizing enzymes after prolonged administration of sex hormones and alcohol in female rats.

    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

    authors: Teschke R,Wannagat FJ,Löwendorf F,Strohmeyer G

    更新日期:1986-02-01 00:00:00

  • Pentosan polysulfate to control hepcidin expression in vitro and in vivo.

    abstract::Hepcidin peptide is crucial in the regulation of systemic iron availability controlling its uptake from the diet and its release from the body storage tissues. Hepcidin dysregulation causes different human disorders ranging from iron overload (e.g. hemochromatosis) to iron deficiency (e.g. anemia). Hepcidin excess is ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2020.113867

    authors: Asperti M,Denardo A,Gryzik M,Castagna A,Girelli D,Naggi A,Arosio P,Poli M

    更新日期:2020-05-01 00:00:00

  • Antimalarial activity of a 4',5'-unsaturated 5'-fluoroadenosine mechanism-based inhibitor of S-adenosyl-L-homocysteine hydrolase.

    abstract::A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl-L-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated with a large increase in the concentr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(90)90562-y

    authors: Bitonti AJ,Baumann RJ,Jarvi ET,McCarthy JR,McCann PP

    更新日期:1990-08-01 00:00:00

  • Inhibition of mammalian tumour thymidylate synthetase by 5-alkylated 2'-deoxyuridine 5'-phosphates.

    abstract::Improved syntheses, based on Lewis acid-catalyzed nucleosidation, are described for the preparation of 5-alkyl-2'-deoxyuridines. These were converted to their 5'-phosphates with the use of wheat shoot phosphotransferase. The dUMP analogues, 5-ethyl-dUMP and 5-propyl-dUMP, were competitive vs dUMP inhibitors of thymidy...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90683-x

    authors: Rode W,Kulikowski T,Kedzierska B,Jastreboff M,Shugar D

    更新日期:1984-09-01 00:00:00

  • PI3K/AKT/mTOR signaling as a molecular target in head and neck cancer.

    abstract::The aim of this review is to summarize current available information about the role of PI3K/AKT/mTOR signaling in head and neck cancer as a potential target for new therapy options. 90% of all head and neck cancers are squamous cell carcinomas (HNSCC). The most common genetic alteration is inactivation of p16 gene whi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.bcp.2019.113729

    authors: Marquard FE,Jücker M

    更新日期:2020-02-01 00:00:00

  • Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression.

    abstract::Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2016.09.022

    authors: Ko JC,Zheng HY,Chen WC,Peng YS,Wu CH,Wei CL,Chen JC,Lin YW

    更新日期:2016-12-15 00:00:00

  • Evidence for separate effects of U73122 on phospholipase C and calcium channels in human platelets.

    abstract::U73122 ((1-[6-(( 17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)exyl]-1H-p yrrole-2,5-dione)) is generally used as a selective inhibitor of phospholipase C (PLC) and the related rise in cytosolic Ca2+. Recently, by using hepatocytes, it was suggested that its action sites are different for PLC activation and increa...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(98)00146-4

    authors: Pulcinelli FM,Gresele P,Bonuglia M,Gazzaniga PP

    更新日期:1998-12-01 00:00:00

  • Trimetazidine prevents palmitate-induced mitochondrial fission and dysfunction in cultured cardiomyocytes.

    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

    authors: Kuzmicic J,Parra V,Verdejo HE,López-Crisosto C,Chiong M,García L,Jensen MD,Bernlohr DA,Castro PF,Lavandero S

    更新日期:2014-10-01 00:00:00

  • A study of the expression of the xenobiotic-metabolising cytochrome P450 proteins and of testosterone metabolism in bovine liver.

    abstract::The expression of xenobiotic-metabolising cytochrome P450 proteins in the liver of cattle was determined using substrate probes and immunologically by Western blot analysis. Compared to the rat, cattle displayed much higher coumarin 7-hydroxylase (CYP2A) and ethoxyresorufin O-deethylase (CYP1) activity but, in contras...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(01)00710-9

    authors: Sivapathasundaram S,Magnisali P,Coldham NG,Howells LC,Sauer MJ,Ioannides C

    更新日期:2001-09-01 00:00:00

  • Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions.

    abstract::The biological mechanisms underlying castration resistance of prostate cancer are not fully understood. In the present study, we examined the role of organic anion transporting polypeptides (OATPs) as importers of dehydroepiandrosterone sulfate (DHEAS) into cells to support growth under androgen-depleted conditions. C...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2012.07.026

    authors: Arakawa H,Nakanishi T,Yanagihara C,Nishimoto T,Wakayama T,Mizokami A,Namiki M,Kawai K,Tamai I

    更新日期:2012-10-15 00:00:00

  • Metabolic changes in fed rats caused by chronic administration of ethyl 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate, a new hypoglycaemic compound.

    abstract::Ethyl 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) is strongly hypoglycaemic in fasted normal and diabetic rats [H. P. O. Wolf, K. Eistetter and G. Ludwig, Diabetologia 22, 456 (1982)]. POCA was fed for 12 weeks to rats on a standard low-fat (3%) diet at levels of 0.05% and 0.2% to give daily intakes of abou...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90242-9

    authors: Koundakjian PP,Turnbull DM,Bone AJ,Rogers MP,Younan SI,Sherratt HS

    更新日期:1984-02-01 00:00:00

  • Antithrombotic and antiplatelet activities of 2-chloro-3-[4-(ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone (NQ12), a newly synthesized 1,4-naphthoquinone derivative.

    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

    authors: Yuk DY,Ryu CK,Hong JT,Chung KH,Kang WS,Kim Y,Yoo HS,Lee MK,Lee CK,Yun YP

    更新日期:2000-10-01 00:00:00

  • Effects of propylthiouracil on D-galactosamine hepatotoxicity in the rat. Evidence for a non-thyroidal effect.

    abstract::The cytoprotective effects of propylthiouracil (PTU) were studied in rats treated with the hepatotoxin D-galactosamine (D-GNH2). Five days of PTU pretreatment prior to D-GNH2 caused hypothyroidism and a significant reduction in liver injury as assessed by serum transaminase levels. When PTU was administered as a singl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90110-2

    authors: Cooper DS,Carter EA,Kieffer JD,Wands JR

    更新日期:1984-11-01 00:00:00

  • Indomethacin and glucocorticoid metabolism in rat liver cytosol.

    abstract::3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50) of rat liver cytosol catalyzes the second step in glucocorticoid metabolism, namely the NADPH-dependent reduction of 5 beta-dihydrocortisol to tetrahydrocortisol. The purified enzyme is potently inhibited by the nonsteroidal anti-inflammatory drugs [Penning and Talala...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90696-9

    authors: Penning TM

    更新日期:1986-12-01 00:00:00

  • Platelet-mediated vascular contractions. Inhibition by flunarizine, a calcium-entry blocker.

    abstract::Flunarizine, a calcium (Ca2+)-entry blocker, selective for vascular tissues, inhibits in a concn-dependent way the contraction of isolated rat caudal artery preparations induced by mediators derived from thrombin-stimulated rat platelets. This inhibition is slow in onset and is of prolonged duration. Specific measurem...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(83)90574-9

    authors: De Clerck F,Van Nueten JM

    更新日期:1983-03-01 00:00:00

  • Electrochemistry of flavonoids. Relationships between redox potentials, inhibition of mitochondrial respiration, and production of oxygen radicals by flavonoids.

    abstract::We have investigated the redox behavior of a series of structurally related flavonoids employing cyclic voltammetry under physiological conditions. The flavonoids that auto-oxidized and produced oxygen radicals had oxidation potentials (E 1/2) significantly lower [-30 to +60 mV vs (SCE)] than those that did not underg...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90253-5

    authors: Hodnick WF,Milosavljević EB,Nelson JH,Pardini RS

    更新日期:1988-07-01 00:00:00

  • Participation of cyclin D1 deregulation in TNP-470-mediated cytostatic effect: involvement of senescence.

    abstract::Inhibition of angiogenesis is becoming one promising, alternative approach to stop tumor from growth and spreading to distant organs. TNP-470, an analog of fumagillin, possesses potent anti-angiogenic effects with minimal toxicity in animal tumor models and is now in the phase III of human cancer trial. Although TNP-4...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2004.05.020

    authors: Lien WH,Chen CK,Lai LY,Chen YH,Wu MP,Wu LW

    更新日期:2004-08-15 00:00:00

  • Properties of the mineralocorticoid receptor immunopurified from bovine kidney.

    abstract::The mineralocorticoid receptor (MCR) from bovine kidney was purified on an affinity column containing covalently linked polyclonal IgG raised in the rabbit against rat kidney protein purified in the presence of RU 26752 that is specific to the MCR. The immuno-affinity eluate was excluded as a single peak during gel pe...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90153-8

    authors: Pagano M,Mirshahi M,Mirshahi F,Monnot M,Lazar G,Chassaing CG,Fermandjian S,Agarwal MK

    更新日期:1994-09-15 00:00:00

  • Redistribution and enhanced urinary excretion of 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) in rats using HCB-specific IgG and Fab fragments.

    abstract::Drug-specific antibody fragments can enhance the elimination of some drugs by redistributing drug from tissues into serum and allowing renal excretion of the drug-antibody complex. This approach could potentially be used to enhance the elimination of compounds such as polychlorinated biphenyls that have very long elim...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90055-8

    authors: Keyler DE,Goon DJ,Shelver WL,Ross CA,Nagasawa HT,St Peter JV,Pentel PR

    更新日期:1994-08-17 00:00:00

  • Effects of the beta 2-adrenoceptor agonist clenbuterol on tyrosine and tryptophan in plasma and brain of the rat.

    abstract::The beta 2-adrenoceptor agonist, clenbuterol (initially 5 mg/kg), was found to significantly reduce plasma tyrosine and raise brain tryptophan levels (P less than 0.01). By comparison, decreases in plasma tryptophan and increases in brain tyrosine were small and often nonsignificant. Amino acid levels measured in diff...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90003-8

    authors: Edwards DJ,Sorisio DA,Knopf S

    更新日期:1989-09-15 00:00:00

  • Inhibition of leukotriene B4 formation in human neutrophils after oral nafazatrom (Bay g 6575).

    abstract::Three grams of nafazatrom (Bay g 6575), given orally to healthy male volunteers in a single dose, significantly reduce the formation of leukotriene B4 in polymorphonuclear leukocytes. LTB4 synthesis fell from 57.1 +/- 17.0 ng/10(7) PMNL, mean +/- S.D., in control to 34.3 +/- 14.4 ng/10(7) PMNL 3 hr after nafazatrom (2...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(85)90304-1

    authors: Strasser T,Fischer S,Weber PC

    更新日期:1985-06-01 00:00:00

  • Effects of acute ethanol administration on the uptake of 59Fe-labeled transferrin by rat liver and cerebellum.

    abstract::The uptake of iron by the liver and cerebellum was measured in rats using [59Fe]transferrin. An acute ethanol load (50 mmol/kg body wt., i.p.) elicited a significant increase in the hepatic and cerebellar non-heme iron concentration. The uptake of 59Fe by the liver and the cerebellum was significantly greater in the e...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90313-1

    authors: Rouach H,Houze P,Gentil M,Orfanelli MT,Nordmann R

    更新日期:1994-05-18 00:00:00

  • Differences between induction effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene and phenobarbitone.

    abstract::The inductive effects of phenobarbitone (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) were compared in C57BL/6J mice. Induction parameters included six substrates: ethylmorphine (EM), benzphetamine (Bph), biphenyl, ethoxycoumarin (EtoC), pentoxyresorufin and dichloro-p-nitroanisole (DPNA). In order to ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90336-5

    authors: Heubel F,Reuter T,Gerstner E

    更新日期:1989-04-15 00:00:00

  • beta-Naphthoflavone-inducible cytochrome P4501A1 activity in liver microsomes of the marine safi fish (Siganus canaliculatus).

    abstract::The cytochrome P450-dependent metabolism of benzo(a)pyrene and other xenobiotics has been investigated in liver microsomes prepared from a local marine safi fish, Siganus canaliculatus. The safi fish was found to have a well-developed microsomal monooxygenase system consisting of cytochrome P450, cytochrome b5 and NAD...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(96)84544-8

    authors: Raza H,Otaiba A,Montague W

    更新日期:1995-10-26 00:00:00

  • Production of adenosine and nucleoside analogs by the exchange reaction catalyzed by rat liver adenosine kinase.

    abstract::We have previously shown [8] that rat liver adenosine kinase can produce [14C]AMP from [14C]adenosine (Ado) and unlabelled adenosine monophosphate (AMP), in the absence of ATP, by an exchange reaction. In this study, we investigated whether Ado or AMP could be replaced in this exchange reaction by other nucleosides or...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(95)02033-0

    authors: Mimouni M,Bontemps F,Van den Berghe G

    更新日期:1995-11-09 00:00:00

  • Opioid-like compound exerts anti-fibrotic activity via decreased hepatic stellate cell activation and inflammation.

    abstract::Hepatic fibrosis is characterized by excess type I collagen deposition and exacerbated inflammatory response. Naltrexone, an opioid receptor antagonist used for treating alcohol abuse, attenuates hepatocellular injury in fibrotic animal models, which can be accompanied by deleterious side effects. Additionally, opioid...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2011.01.015

    authors: Day SA,Lakner AM,Moore CC,Yen MH,Clemens MG,Wu ES,Schrum LW

    更新日期:2011-04-15 00:00:00

  • Binding of nitropyrenes and benzo[a]pyrene to mouse lung deoxyribonucleic acid after pretreatment with inducing agents.

    abstract::In assessing the biological effects of exposure to a complex chemical mixture, it is important to determine how the behavior of one compound may be influenced by the presence of other compounds in the mixture. In this study the effect of pre-exposure to an organic extract of diesel exhaust or to selected compounds in ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90581-2

    authors: Howard AJ,Mitchell CE,Dutcher JS,Henderson TR,McClellan RO

    更新日期:1986-07-01 00:00:00