Abstract：
:As theophylline, caffeine and acetaminophen (APAP) are commonly found in combination in prescription and non-prescription drugs, the present study was designed to evaluate changes of hepatic glutathione (GSH) and lipid peroxidation in rats treated concurrently with these widely used drugs. In rats treated with different doses of theophylline, a dose-related depletion of hepatic GSH was observed (r = -0.88, P < 0.001). After a dose of 100 mg/kg of caffeine given alone and in combination with 50 mg/kg of theophylline, hepatic GSH levels were decreased by 22.5% (P > 0.05) and 35.5% (P < 0.01) of the control value, respectively. Also, the challenge with 500 mg/kg of APAP significantly depleted hepatic GSH in rats pretreated with either saline or the combination of both theophylline and caffeine (50 and 100 mg/kg, respectively), P < 0.001. In the latter group, hepatic GSH levels were approximately 47% of the corresponding values in rats that received APAP (P < 0.02). Such severe depletion of hepatic GSH, in rats that received the three drugs, was associated with a significant rise in the extent of lipid peroxidation (P < 0.05). The other experimental groups treated with one or two drugs did not exhibit similar changes. These results suggest that the concomitant administration of theophylline, caffeine and APAP may enhance the susceptibility of the liver cells to the toxic effect of APAP by severely depleting hepatic GSH with subsequent induction of lipid peroxidation.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Farag MM,Abdel-Meguid EMdoi
10.1016/0006-2952(94)90173-2subject
Has Abstractpub_date
1994-02-09 00:00:00pages
443-6issue
3eissn
0006-2952issn
1873-2968pii
0006-2952(94)90173-2journal_volume
47pub_type
杂志文章abstract：:The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. Th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.12.017
更新日期：2008-04-01 00:00:00
abstract：:Anticoagulants and anti-platelet agents are simultaneously administrated in clinical practice (i.e. percutaneous coronary intervention), which cause significant risk of systemic bleeding. Targeted delivery of anticoagulants to the activated platelets at sites of vascular injuries may condense the site-specific anticoa...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.04.004
更新日期：2015-06-15 00:00:00
abstract：:Pyridine N-oxide derivatives represent a new class of anti-HIV compounds for which some members exclusively inhibit HIV-1 RT, whereas other members act, additionally or alternatively, at a post-integrational event in the replicative cycle of HIV. A prototype pyridine N-oxide derivative, JPL-32, inhibited tumor necrosi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.12.025
更新日期：2006-04-14 00:00:00
abstract：:PepT1 (SLC15A1) is a high-capacity low-affinity transporter that is important in the absorption of digested di/tripeptides from dietary protein in the small intestine. PepT1 is also crucial for the intestinal uptake and absorption of therapeutic agents such as the β-lactam aminocephalosporins and antiviral prodrugs. S...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.03.008
更新日期：2016-05-01 00:00:00
abstract：:The mechanism of activation of microsomal glutathione transferase in isolated liver cells by diisapropylidene acetone (phorone) was investigated. Phorone (1 mM) causes a time-dependent increase (up to 2.6-fold) in the glutathione transferase activity of microsomes isolated from treated hepatocytes. Since phorone react...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90269-o
更新日期：1992-01-22 00:00:00
abstract：:Intracellular cyclic AMP accumulation following exposure to dopamine (DA) agonists and and antagonists was measured in striatal slices from rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway and which showed contralateral circling to apomorphine. Both DA (10-320 microM) and the D-1 a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90040-p
更新日期：1992-07-07 00:00:00
abstract：:The ability of gold coordination complexes to bind to DNA and produce inter-strand cross-links in DNA was assessed in an assay system based on the fluorescence properties of the DNA intercalative dye, ethidium bromide. Results from these studies using a variety of gold(I) and gold(III) complexes suggest that the abili...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90107-3
更新日期：1986-05-01 00:00:00
abstract：:Dimercaptosuccinic acid (DMSA) was shown to lower blood pressure in rat models of arterial hypertension. Thus, there is evidence that-besides its chelating properties-DMSA has a direct vascular effect, e.g. through scavenging of reactive oxygen species (ROS). We speculated that, in addition, intracellular calcium mobi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00121-7
更新日期：2003-05-15 00:00:00
abstract：:Cisplatin is a potent chemotherapeutic drug widely used for the treatment of human cancer. However, its efficacy against hepatocellular carcinoma (HCC) is poor for reasons that remain unclear. We show here that prothymosin-alpha (PTMA) is overexpressed in HCC cell lines. Silencing PTMA using short-hairpin RNA sensitiz...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.10.003
更新日期：2016-12-15 00:00:00
abstract：:Neutrophils play a key role in host defense and inflammation through the production of superoxide anion and other reactive oxygen species (ROS) by the enzyme complex NADPH oxidase. The cytosolic NADPH oxidase component, p67phox, has been shown to be phosphorylated in human neutrophils but the pathways involved in this...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.07.070
更新日期：2011-11-01 00:00:00
abstract：:Glipentide, a second generation sulfonylurea, raised the cellular concentration of fructose 2,6-bisphosphate in isolated rat hepatocytes. Parallel to accumulating this regulatory metabolite, glipentide inhibited basal gluconeogenesis and increased the rate of L-lactate production, as well as the metabolic flux through...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90317-6
更新日期：1988-08-15 00:00:00
abstract：:The transient receptor potential vanilloid-4 (TRPV4) belongs to a family of ion channels and can be activated by warm temperature, hypotonicity, cell swelling or lipid mediators of the arachidonic cascade. The metabolites or events responsible for TRPV4 activation are associated with inflammation, arguing in favor of ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2014.01.005
更新日期：2014-05-15 00:00:00
abstract：:JG-03-14, a substituted pyrrole that inhibits microtubule polymerization, was screened against MCF-7 (p53 wild type), MDA-MB231 (p53 mutant), MCF-7/caspase 3 and MCF-7/ADR (multidrug resistant) breast tumor cell lines. Cell viability and growth inhibition were assessed by the crystal violet dye assay. Apoptosis was ev...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.07.003
更新日期：2007-10-01 00:00:00
abstract：:We hypothesized that the histamine H(3)-receptor (H(3)R)-mediated attenuation of norepinephrine (NE) exocytosis from cardiac sympathetic nerves results not only from a Galpha(i)-mediated inhibition of the adenylyl cyclase-cAMP-PKA pathway, but also from a Gbetagamma(i)-mediated activation of the MAPK-PLA(2) cascade, c...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.01.001
更新日期：2007-04-15 00:00:00
abstract：:Treatment of human, peripheral blood neutrophils with gamma-interferon both "primed" their ability to generate reactive oxidants and increased their rate of protein synthesis. This increased rate of protein synthesis was greatest 60 min after the addition of 100 U/ml gamma-interferon and was not due to an increased in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90329-8
更新日期：1989-04-15 00:00:00
abstract：:Acetaminophen (AP) is a widely-used analgesic agent that has been linked to human liver and kidney disease with prolonged or high-dose usage. In rodents, the target organs that are affected include liver, kidney, and the olfactory mucosa. AP toxicity requires cytochrome P450(CYP)-mediated metabolic activation, and the...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00004-5
更新日期：1998-06-01 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：: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
doi：10.1016/s0006-2952(01)00767-5
更新日期：2001-11-01 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：:Several growth factor receptors undergo shedding from the cell surface as a result of limited proteolysis via mechanisms that are at present poorly understood. By Western blotting of the conditioned media and cell lysates of several cell lines expressing the hepatocyte growth factor receptor, we found that suramin, a ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00219-p
更新日期：1995-09-28 00:00:00
abstract：:In activation of 12-lipoxygenase (12-LO) in mouse epidermal homogenate by the antipsoriatic drug anthralin has been studied in detail. In view of the chemical instability of anthralin in a physiological buffer, the biological effects ascribed to the molecule itself may be related to some of its breakdown products. How...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(96)00043-3
更新日期：1996-05-03 00:00:00
abstract：:Developmental correlation of higher levels of estrogen binding by macromolecules in rat liver supernatant and of increases in plasma renin substrate levels after estrogen administration is reported. Gel filtration columns were used to separate bound from free radioactivity in studying binding of radioactive estradiol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(77)90467-1
更新日期：1977-05-15 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：:Bufuralol hydroxylation activities of liver microsomal cytochrome P450 (P450) enzymes were studied in the rat; the reaction has been used widely in determining levels of liver microsomal P450 2D6, which shows debrisoquine-type genetic polymorphism in humans. Liver microsomes catalyzed the conversion of bufuralol to 1'...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90069-8
更新日期：1994-06-01 00:00:00
abstract：:Cytogenetic lesions often alter kinase signaling in acute myeloid leukemia (AML) and the addition of kinase inhibitors to the treatment arsenal is of interest. We have screened a kinase inhibitor library and performed combination testing to find promising drug-combinations for synergistic killing of AML cells. Cytotox...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.08.020
更新日期：2016-10-15 00:00:00
abstract：:Distribution of liposome-encapsulated [(125)I]iodixanol in different types of liver cells following intravenous injection was studied in rats. The data showed that liposome-encapsulated [(125)I]iodixanol was rapidly taken up by the liver; after 15 min, radioactivity corresponding to nearly 25% of the injected radioact...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00364-6
更新日期：2000-08-15 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：:With the aid of a chiral derivatizing reagent and a sensitive and specific nitrogen-phosphorus gas chromatographic assay, metabolism of para-chloroamphetamine (PCA) enantiomers has been studied following incubation of racemic (RS)-, R(-)- and S(+)-PCA with rabbit liver microsomal preparations. Significant metabolism o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90228-3
更新日期：1982-01-01 00:00:00
abstract：:P-450-male is a male specific form of cytochrome P-450 in rat liver microsomes. Cytochrome P-450 crossreactive with anti-P-450-male antibodies was purified to an electrophoretical homogeneity from liver microsomes of male beagle dogs. The specific content of the purified cytochrome P-450 (P-450-D1) was 16.9 nmol/mg pr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90032-4
更新日期：1989-01-15 00:00:00
abstract：:Sulphate conjugation was investigated using extracts of human foetal liver cells in culture. The three reactions which are involved in sulphate conjugation were measured singly or in combination: they are (i) the PAPS generation catalyzed by ATP-sulphurylase and adenosine 5'-phosphosulphate (APS)-kinase, (ii) the phen...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90331-0
更新日期：1988-12-15 00:00:00
