Abstract:
:Glucose metabolism and hemoglobin reactivity in intact human erythrocytes were assessed in the presence of the tryptophan metabolites, 3-hydroxyanthranilate (3-HAT), quinolinate and picolinate. Of these compounds, only 3-HAT altered red cell oxidative status by inducing, in a dose-dependent manner, formation of methemoglobin and non-functional oxidation products of hemoglobin, and by increasing both net glycolytic flux and flux through the hexose monophosphate shunt. 3-HAT also decreased the normal lactate to pyruvate production ratio with pyruvate accumulating at the expense of lactate. These findings are consistent with the auto-oxidative reactivity of quinolinate, picolinate, and 3-HAT in that only 3-HAT undergoes base-catalyzed auto-oxidation (Dykens et al., Biochem Pharmacol 36: 211-217, 1987). Lactate and pyruvate added to the medium in physiologic concentrations uncoupled oxidative glycolysis from reductive glycolysis, resulting in accumulation of pyruvate in the presence of 3-HAT with little increase in total glycolytic flux. Superoxide dismutase (SOD), which accelerates 3-HAT auto-oxidation in vitro (Dykens et al., Biochem Pharmacol 36: 211-217, 1987), exacerbated HAT-mediated oxidative insult by increasing methemoglobin formation, hexose monophosphate shunt flux, and pyruvate accumulation. Persistence of 3-HAT-induced red cell metabolic responses and oxidative damage in the presence of SOD, DETAPAC (diethylenetriaminepentaacetic acid) and formate suggests that an organic-based radical, perhaps the anthranilyl radical produced during 3-HAT auto-oxidation, is the proximate agent exerting oxidative stress. Slow rates of auto-oxidation indicate that 3-HAT may be useful as a probe of antioxidant mechanisms in normal and diseased red blood cells.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Dykens JA,Sullivan SG,Stern Adoi
10.1016/0006-2952(89)90301-8subject
Has Abstractpub_date
1989-05-15 00:00:00pages
1555-62issue
10eissn
0006-2952issn
1873-2968pii
0006-2952(89)90301-8journal_volume
38pub_type
杂志文章abstract::The present investigation addressed the role of verapamil for oral pharmacokinetics of morphine-6-beta-glucuronide (M6G). Male Sprague-Dawley rats received 62.5 mg kg(-1) M6G-dihydrate orally w/wo pre-treatment with 70 mg kg(-1) verapamil. Intravenous M6G (3.9 mg kg(-1) ) and oral morphine (52.7 mg kg(-1) morphine-hyd...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)00881-x
更新日期:2002-04-15 00:00:00
abstract::This paper presents data on the effects of benfluron and its two metabolites DBF and NOBF on both endogenous and exogenous, respiration in the presence of succinate as substrate, of both P388 murine leukemia and Ehrlich ascites carcinoma cells. The most efficient inhibitors of endogenous and exogenous respiration were...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90413-y
更新日期:1991-12-11 00:00:00
abstract::Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary betwe...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.07.024
更新日期:2018-09-01 00:00:00
abstract::ERCC1 is a critical gene within the nucleotide excision repair pathway. Overexpression of ERCC1 through promoter-mediating transcriptional regulation is associated with repair of cisplatin-induced DNA damage and clinical resistance to platinum-chemotherapy. Several transcriptional repressors and activators within the ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.12.015
更新日期:2006-03-14 00:00:00
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
更新日期:2001-09-01 00:00:00
abstract::Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enz...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90084-1
更新日期:1989-08-01 00:00:00
abstract::Most studies have reported an up-regulation of retinoic acid receptor (RAR) mRNA expression by all-trans retinoic acid (RA). We aimed to study the effect of RA on RAR protein levels in MCF-7 human breast cancer cells. Incubation of these cells with 10(-6) M RA induced a rapid breakdown of both RARalpha and RARgamma in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00600-1
更新日期:2001-06-01 00:00:00
abstract::Exposure of lung tissue to Co(II) ions both in vivo and in vitro results in toxicity, a relatively early event of which is the oxidation of cellular glutathione. In this study we have attempted to delineate the relationship between this oxidation of glutathione and the subsequent development of cellular dysfunction. S...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90573-2
更新日期:1992-02-04 00:00:00
abstract::It has been reported that nonsteroidal anti-inflammatory drugs (NSAIDs) suppress bone repair and bone remodeling but only mildly inhibit bone mineralization at the earlier stage of the repair process. We proposed that the proliferation and/or the earlier stage of differentiation of osteoblasts may be affected by NSAID...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00186-0
更新日期:1999-09-15 00:00:00
abstract::The tyrosine kinase inhibitors (TKIs) and multikinase inhibitors (MKIs) are oncology drugs of increasing importance that have improved the treatment of multiple tumors types. In some patients these agents produce adverse effects, including pharmacokinetic drug-drug interactions, due to cytochrome P450 (CYP) inhibition...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2014.01.016
更新日期:2014-03-15 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::Chemical compounds derived from plants have been used since the origin of human beings to counteract a number of diseases. Among them, the natural isoquinoline alkaloid berberine has been employed in Ayurvedic and Chinese Medicine for hundreds of years with a wide range of pharmacological and biochemical effects. More...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2012.07.018
更新日期:2012-11-15 00:00:00
abstract::Thermodynamic parameters DeltaG degrees , DeltaH degrees and DeltaS degrees of the binding equilibrium of 12 ligands (six agonists and six antagonists) to the A(2B) adenosine receptor subtype have been determined by affinity measurements carried out on HEK 293 cells stably transfected with human A(2B) adenosine recept...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.09.003
更新日期:2008-01-15 00:00:00
abstract::Isolated liver from phenobarbital-induced male mice was perfused using infusions of cytochrome c pulses as quality control of the system. Livers spontaneously evolved 1.1 pmoles ethane g-1 liver min-1, exogenous pentane disappeared with 0.6 pmoles g-1 min-1. Infusion of 0.26 mmoles/l. FeCl2 led to immediate ethane pro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90112-0
更新日期:1983-06-01 00:00:00
abstract::Combining site-directed mutagenesis with information obtained from molecular modelling of the bradykinin (BK) human B2 receptor (hB2R) as derived from the bovine rhodopsin crystal structure [Science 289 (2000) 739], we previously defined a putative binding mode for the non-peptide B2 receptor antagonists, FR173657 and...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.09.034
更新日期:2004-02-15 00:00:00
abstract::Epoxide hydrolase activity was determined in hepatic microsomes of adult males of 22 rat strains. The specific activity varied between 4.3 and 12.7 nmole styrene glycol/mg protein per min. The enzyme in F344, DA and Sprague--Dawley rats, strains with low, high and intermediate activity, respectively, was studied in mo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90125-9
更新日期:1983-06-01 00:00:00
abstract::Liver mitochondrial low-Km aldehyde dehydrogenase (ALDH2, EC 1.2.1.3), the isoform responsible for the conversion of acetaldehyde to acetate, is inhibited by the sulfoxide bioactivation products of Et2NC(O)SMe (from the alcohol aversion drug disulfiram), Pr2NC(O)SEt (the herbicide S-ethyl N,N-dipropylthiocarbamate), a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00239-7
更新日期:1999-11-01 00:00:00
abstract::Stress, be it from environmental factors or intrinsic to the cell as result of growth and metabolism, can be harmful to cells. Mammalian cells have developed numerous mechanisms to respond to diverse forms of stress. These mechanisms combine signaling cascades and activation of gene expression programs to orchestrate ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.07.002
更新日期:2006-11-30 00:00:00
abstract::Naturally soluble rat germ cell adenylate cyclase was inhibited by adenosine and the adenosine analogs, 9-beta-D-arabinofuranosyl adenine (AFA) and 2',5'-dideoxyadenosine (DDA), all of which inhibited hormone-sensitive adenylate cyclases at the "P" site. The IC50 values for adenosine and DDA were approximately 0.1 and...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90487-4
更新日期:1987-06-15 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::To firmly establish the pathway involved in ligand-induced degradation of the AHR, cell lines derived from mouse rat or human tissues were exposed to inhibitors specific to the proteasome or calpain proteases and exposed to TCDD. The level of endogenous AHR and CYP1A1 protein was then evaluated by quantitative Western...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.03.021
更新日期:2007-06-30 00:00:00
abstract::Calcium signaling robustly inhibits AC6 activity in membrane preparations and in intact cells via capacitative calcium entry (CCE). However, the release of intracellular calcium has not been demonstrated to robustly alter AC6 signaling and activation of Galpha(q)-coupled receptors in tissues that express AC6 enhances ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2005.04.007
更新日期:2005-07-01 00:00:00
abstract::Mevinolin is a potent competitive inhibitor of HMG-CoA reductase, the enzyme catalyzing the major rate-limiting step in cholesterol synthesis. In this study the drug was administered as an intragastric dose at 2.5 mg/kg/day to 10 to 12-week-old lean and obese Zucker female rats over a 5-day period. Mevinolin showed no...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90179-1
更新日期:1987-03-15 00:00:00
abstract::In a variety of malignant cells the prostate-apoptosis-response-gene-4 (Par-4) induces increased sensitivity towards chemotherapeutic agents by down-regulating anti-apoptotic B-cell lymphoma-gene 2 (Bcl-2). Hypothesizing that Par-4 also influences apoptosis in myeloid cell lines, we tested this hypothesis by stably tr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.02.028
更新日期:2004-07-01 00:00:00
abstract::The flavone L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] delayed the progression of aphidicolin-synchronized MDA-468 breast carcinoma cells through S phase and prevented progression through G2. L86-8275 prevented the G2-related increase in histone H1 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90590-s
更新日期:1993-11-17 00:00:00
abstract::The protein tyrosine kinase Src is expressed widely in the central nervous system and is abundant in neurons. Over the past several years, evidence has accumulated showing that one function of Src is to regulate the activity of N-methyl-D-aspartate (NMDA) receptors and other ion channels. NMDA receptors are a principa...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(98)00124-5
更新日期:1998-10-01 00:00:00
abstract::The microsomal brush-border fraction of rat renal tissue contains enzymatic activity, optimally active at pH 9, that is capable of degrading human myelin basic protein (BP) peptide 43-88. In the present study, this degradation and the effect on it of selected drugs and hormones were examined further. Of the substances...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90500-3
更新日期:1985-04-15 00:00:00
abstract::The major metabolic products of the endogeneous catecholamine dopamine are its 3- and 4-O-sulphates which have also been implicated as intermediates in noradrenaline biosynthesis. Because of the unsatisfactory status of the literature concerning the synthesis, isolation, purity and characterisation of the dopamine O-s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90115-0
更新日期:1982-07-01 00:00:00
abstract::In isolated hepatic nuclei, the heavy metals Zn2+ and Cu2+ (10 microM) inhibited Ca2+ uptake and caused a prompt release of Ca2+ from preloaded nuclei in a concentration-dependent manner, with Zn2+ being more effective than Cu2+. The sulfhydryl group reducing agent dithiothreitol (DTT) protected the nuclei from the ef...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90180-5
更新日期:1993-02-24 00:00:00
abstract::Isoliquiritigenin (ILTG) is a flavonoid with chalcone structure (4,2',4'-trihydroxychalcone), an active component present in plants like Glycyrrhiza and Dalbergia which showed various biological activities including anti-inflammatory, anti-carcinogenic and antihistamic. As very little is known in regard to the underly...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.01.015
更新日期:2007-05-15 00:00:00