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


: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 elimination half-lives. As a first step in testing this hypothesis, the effects of 2,2',4,4',5,5'-hexachlorobiphenyl (HCB)-specific antibodies and their corresponding Fab fragments on HCB disposition were studied in rats. Antibodies to HCB were produced in chickens, and the corresponding Fab fragments were produced by digestion with papain. To study antibody effects on HCB distribution, [14C]HCB (0.1 mg) was administered i.v. to rats. Two weeks later, after distribution to tissues was complete, anti-HCB IgG or control IgG was administered i.v. The serum radiolabel concentration 2 hr after IgG administration increased 185 +/- 64% in animals treated with specific antibody vs 51 +/- 19% in control animals (P < 0.001). The increase in serum radiolabel concentration was apparent within 30 min and maximal at 2 hr. To study effects on HCB excretion, anti-HCB or control Fab fragment was administered 2 weeks after [14C]HCB. Urinary HCB excretion over the next 24 hr, measured by gas chromatography, was 10-fold greater in the group treated with anti-HCB Fab (P < 0.01). These data demonstrate that anti-HCB IgG can redistribute HCB rapidly from tissues into serum and that anti-HCB Fab can enhance urinary HCB excretion. While the magnitude of these changes was small, the data suggest that increasing HCB excretion using drug-specific antibody fragments is feasible, and can serve as a model for enhancing the excretion of compounds that have very long elimination half-lives.


Biochem Pharmacol


Biochemical pharmacology


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




Has Abstract


1994-08-17 00:00:00














  • Effects of suramin on increases in cytosolic calcium and on inhibition of adenylate cyclase induced by adenosine 5'-diphosphate in human platelets.

    abstract::The effects of the P2-purinoceptor antagonist, suramin, on ADP-induced increases in human platelet cytosolic calcium concentration ([Ca2+]i) and inhibition of prostaglandin E1 (PGE1)-stimulated adenylate cyclase activity were investigated. Suramin (50-200 microM) acted as an antagonist of ADP-induced increases in [Ca2...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hall DA,Hourani SM

    更新日期:1994-03-15 00:00:00

  • Debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities in bovine and rabbit tissues.

    abstract::The tissue distributions of debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities in microsomes from bovine and rabbit tissues were analysed. Debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities were found in liver, and at low levels in cerebral cortex, kidney cortex, lung, small int...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Matsuo Y,Iwahashi K,Ichikawa Y

    更新日期:1992-05-08 00:00:00

  • Indomethacin and glucocorticoid metabolism in rat liver cytosol.

    abstract::3 alpha-Hydroxysteroid dehydrogenase (EC 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


    authors: Penning TM

    更新日期:1986-12-01 00:00:00

  • Thiourea toxicity in mouse C3H/10T1/2 cells expressing human flavin-dependent monooxygenase 3.

    abstract::Human flavin-dependent monooxygenase (FMO) isoforms 1 and 3 were expressed by retroviral gene transfer in mouse C3H/10T1/2 cells. FMO function was determined by the sulfoxidation of p-tolylmethylsulfide (TMS). Enzyme activity ranged from 4 to 30 nmol p-tolylmethylsulfoxide (TMSO)/30 min/mg cell protein for FMO 3 clone...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Smith PB,Crespi C

    更新日期:2002-06-01 00:00:00

  • Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro.

    abstract::Resistance to anti-cancer chemotherapies often leads to regional failure, and can be caused by biochemical and/or physiological mechanisms. Biochemical mechanisms include the overexpression of resistance-conferring proteins. In contrast, physiological resistance involves the tumor microenvironment, and can be caused b...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Mahoney BP,Raghunand N,Baggett B,Gillies RJ

    更新日期:2003-10-01 00:00:00

  • Regulation of eicosanoid biosynthesis in the macrophage. Involvement of protein tyrosine phosphorylation and modulation by selective protein tyrosine kinase inhibitors.

    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


    authors: Glaser KB,Sung A,Bauer J,Weichman BM

    更新日期:1993-02-09 00:00:00

  • In vitro [3H]-erythromycin binding to Staphylococcus aureus.

    abstract::Characteristics of erythromycin binding to Staphylococcus aureus were determined by using kinetics and equilibrium binding experiments. Both methods yielded identical values of the dissociation constant, i.e. 0.1 muM. This value was in accord with that found with a bacterial extract of ribosomes which are the organell...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Barre J,Fournet MP,Zini R,Deforges L,Duval J,Tillement JP

    更新日期:1986-03-15 00:00:00

  • Actin cytoskeleton, tubular sodium and the renal synthesis of dopamine.

    abstract::The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Soares-da-Silva P

    更新日期:1992-11-03 00:00:00

  • Carbamazepine metabolism to a reactive intermediate by the myeloperoxidase system of activated neutrophils.

    abstract::Carbamazepine is an anticonvulsant which is associated with a significant incidence of hypersensitivity reactions including agranulocytosis. We have postulated that many drug hypersensitivity reactions, especially agranulocytosis and lupus, are due to reactive metabolites generated by the myeloperoxidase (MPO) (EC 1.1...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Furst SM,Uetrecht JP

    更新日期:1993-03-24 00:00:00

  • Interaction of 2,4-dichlorophenoxyacetate (2,4-D) and 2,4,5-trichlorophenoxyacetate (2,4,5-T) with the acyl-CoA: amino acid N-acyltransferase enzymes of bovine liver mitochondria.

    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


    authors: Kelley M,Vessey DA

    更新日期:1986-01-15 00:00:00

  • Modulation effects of cyclosporine on etoposide pharmacokinetics and CNS distribution in the rat utilizing microdialysis.

    abstract::In the present study, we evaluated the pharmacokinetics of the chemotherapeutic agent etoposide (ET) under steady-state conditions and examined its extent of distribution into the CNS of conscious animals. An i.v. infusion of 15 mg/kg/hr was administered to nine rats. Each of the nine rats also received the potent mul...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Burgio DE,Gosland MP,McNamara PJ

    更新日期:1996-04-12 00:00:00

  • 5-Substituted-2,2'-anhydrouridines, potent inhibitors of uridine phosphorylase.

    abstract::5-Substituted-2,2'-anhydrouridines are a new class of competitive inhibitors of uridine phosphorylase. The most potent member of the series is 2,2'-anhydro-5-ethyluridine with an apparent Ki value of 25 nM. These compounds are selective inhibitors of uridine phosphorylase and have no effect on thymidine phosphorylase....

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Veres Z,Szabolcs A,Szinai I,Dénes G,Kajtár-Peredy M,Otvös L

    更新日期:1985-05-15 00:00:00

  • Oxidative dehalogenation of 2-fluoro-17 alpha-ethynyloestradiol in vivo. A distal structure-metabolism relationship of 17 alpha-ethynylation.

    abstract::Metabolic activation to catechols and their oxidation products is variously considered to contribute to the genotoxic, cytotoxic, transforming and tumour-promoting activities of exogenous steroidal oestrogens. 2-Fluoro-17 alpha-ethynyloestradiol (2-FEE2) was synthesized as a prototype of pharmacologically active deriv...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Morgan P,Maggs JL,Page PC,Park BK

    更新日期:1992-11-03 00:00:00

  • Metabolic activation of hydralazine by rat liver microsomes.

    abstract::There is evidence to suggest that the oxidative metabolism of hydralazine (HP), an antihypertensive drug, may represent a toxic pathway which could account for some of the adverse effects of the drug. Experiments were done to determine whether the hepatic oxidative metabolism of HP is associated with the formation of ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: LaCagnin LB,Colby HD,Dalal NS,O'Donnell JP

    更新日期:1987-08-15 00:00:00

  • The preferential homing of a platelet derived growth factor receptor-recognizing macromolecule to fibroblast-like cells in fibrotic tissue.

    abstract::Platelet derived growth factor (PDGF) is a key factor in the induction and progression of fibrotic diseases with the activated fibroblast as its target cell. Drug targeting to the PDGF-receptor is explored as a new approach to treat this disease. Therefore, we constructed a macromolecule with affinity for the PDGF-bet...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Beljaars L,Weert B,Geerts A,Meijer DK,Poelstra K

    更新日期:2003-10-01 00:00:00

  • Catalase expression in MCF-7 breast cancer cells is mainly controlled by PI3K/Akt/mTor signaling pathway.

    abstract::Catalase is an antioxidant enzyme that catalyzes mainly the transformation of hydrogen peroxide into water and oxygen. Although catalase is frequently down-regulated in tumors the underlying mechanism remains unclear. Few transcription factors have been reported to directly bind the human catalase promoter. Among them...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Glorieux C,Auquier J,Dejeans N,Sid B,Demoulin JB,Bertrand L,Verrax J,Calderon PB

    更新日期:2014-05-15 00:00:00

  • Expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes during cell cycle traverse.

    abstract::The expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes was analyzed in cell cycle phase enriched populations of doxorubicin-resistant murine leukemic P388/R-84 cells. Flow cytometric analysis of bromodeoxyuridine (BrdU) incorporation and staining with anti-BrdU antibodies was used to co...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ramachandran C,Mead D,Wellham LL,Sauerteig A,Krishan A

    更新日期:1995-02-14 00:00:00

  • Blockade of LTB4-induced chemotaxis by bioactive molecules interfering with the BLT2-Galphai interaction.

    abstract::BLT2, a low-affinity leukotriene B4 (LTB4) receptor, is a member of the G-protein coupled receptor (GPCR) family and is involved in the pathogenesis of inflammatory diseases such as asthma. Despite its clinical implications, however, no pharmacological inhibitors are available. In the present study, we screened for sm...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kim JY,Lee WK,Yu YG,Kim JH

    更新日期:2010-05-15 00:00:00

  • Role of cytochrome P450 1A2 in bilirubin degradation Studies in Cyp1a2 (-/-) mutant mice.

    abstract::In congenital jaundice, which is due to defects of bilirubin gluruconidation, bilirubin is degraded by an alternative pathway into unidentified products. Previously, it was shown that plasma bilirubin levels can be decreased in rats with this defect by inducers of CYP1A enzymes. Here, liver microsomes from rats or mic...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Zaccaro C,Sweitzer S,Pipino S,Gorman N,Sinclair PR,Sinclair JF,Nebert DW,De Matteis F

    更新日期:2001-04-01 00:00:00

  • Cetaben and fibrates both influence the activities of peroxisomal enzymes in different ways.

    abstract::The effects of cetaben and clofibric acid were compared on the activities of peroxisomal enzymes in the liver and kidney of male Wistar rats. Cetaben at 200 mg/kg body wt increased the activities of all of the enzymes in the liver that were studied two to eight times, whereas the changes induced by the same dose of cl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Chandoga J,Rojeková I,Hampl L,Hocman G

    更新日期:1994-02-09 00:00:00

  • Catalytic effect of serum albumin on the o-rearrangement of N-sulfooxy-2-acetylaminofluorene, a potential hepatocarcinogen in the rat, to nonmutagenic sulfuric acid esters of o-amidofluorenols.

    abstract::Bovine serum albumin (BSA) catalyzes the o-rearrangement of the reactive electrophile, N-sulfooxy-2-acetylaminofluorene (NSF), a potential ultimate hepatocarcinogen in the rat, to the nonmutagenic sulfuric acid esters of 1- and 3-hydroxy-2-acetylaminofluorene. Conversion of NSF was proportional to BSA concentrations r...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Smith BA,Gutmann HR,Springfield JR

    更新日期:1989-11-15 00:00:00

  • Inhibitions of acid secretion by E3810 and omeprazole, and their reversal by glutathione.

    abstract::A substituted benzimidazole ([4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methylsulfinyl)- 1H-benzimidazole sodium salt (E3810), is a gastric proton pump (H+, K(+)-ATPase) inhibitor. E3810 and omeprazole inhibited acid accumulation dose dependently as measured with aminopyrine uptake in isolated rabbit gastric glands, ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Fujisaki H,Shibata H,Oketani K,Murakami M,Fujimoto M,Wakabayashi T,Yamatsu I,Yamaguchi M,Sakai H,Takeguchi N

    更新日期:1991-07-05 00:00:00

  • NADH fluorescence in isolated guinea-pig and rat cardiomyocytes exposed to low or high stimulation rates and effect of metabolic inhibition with cyanide.

    abstract::In this study we investigated whether NADH fluorescence levels changed in response to low or high rates of electrical stimulation in single ventricular myocytes isolated from rat and guinea-pig hearts, either during a single contraction or upon sustained electrical stimulation of cells. NADH levels were determined fro...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Griffiths EJ,Lin H,Suleiman MS

    更新日期:1998-07-15 00:00:00

  • Iron interactions and other biological reactions mediating the physiological and toxic actions of manganese.

    abstract::Chronic exposure to the divalent heavy metals, such as iron, lead, manganese (Mn), and chromium, has been linked to the development of severe, often irreversible neurological disorders and increased vulnerability to developing Parkinson's disease. Although the mechanisms by which these metals elicit or facilitate neur...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Roth JA,Garrick MD

    更新日期:2003-07-01 00:00:00

  • Cocaine-protein targets in mouse liver.

    abstract::Cocaine has been shown to be hepatotoxic in mice, rats and humans. N-Oxidative metabolism of cocaine is required for this effect, and it has been proposed that binding of cocaine reactive metabolites formed via this pathway might be responsible for cytotoxicity. To explore this hypothesis, cocaine-protein adducts in l...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ndikum-Moffor FM,Roberts SM

    更新日期:2003-07-01 00:00:00

  • Influence of the anesthetic 2,6-diisopropylphenol on the oxidative phosphorylation of isolated rat liver mitochondria.

    abstract::Isolated rat liver mitochondria have been incubated in the presence of the general anesthetic 2,6-diisopropylphenol (0-100 microM) and the efficiency of oxidative phosphorylation has been evaluated by measuring the respiratory rates, the rates of ATP synthesis or hydrolysis and the magnitude of the transmembrane elect...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Branca D,Roberti MS,Lorenzin P,Vincenti E,Scutari G

    更新日期:1991-06-21 00:00:00

  • Effects of purified green and black tea polyphenols on cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid in human colon mucosa and colon tumor tissues.

    abstract::The effects of green and black tea polyphenols on cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in normal human colon mucosa and colon cancers were investigated. At a concentration of 30 microg/mL, (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatech...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hong J,Smith TJ,Ho CT,August DA,Yang CS

    更新日期:2001-11-01 00:00:00

  • Sorafenib suppresses TGF-β responses by inducing caveolae/lipid raft-mediated internalization/degradation of cell-surface type II TGF-β receptors: Implications in development of effective adjunctive therapy for hepatocellular carcinoma.

    abstract::Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Chung CL,Wang SW,Sun WC,Shu CW,Kao YC,Shiao MS,Chen CL

    更新日期:2018-08-01 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


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

    更新日期:1986-07-01 00:00:00

  • Dipyridamole analogs as pharmacological inhibitors of equilibrative nucleoside transporters. Identification of novel potent and selective inhibitors of the adenosine transporter function of human equilibrative nucleoside transporter 4 (hENT4).

    abstract::To identify needed human equilibrative nucleoside transporter 4 (hENT4) inhibitors, we cloned and stably expressed the recombinant protein in PK15NTD (nucleoside transporter deficient) cells, and, investigated its interaction with a series of dipyridamole analogs synthesized in our laboratory. Compounds were tested in...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wang C,Lin W,Playa H,Sun S,Cameron K,Buolamwini JK

    更新日期:2013-12-01 00:00:00