Abstract:
:The cytoprotective effect of curcumin, a natural constituent of Curcuma longa, on the cytotoxicity of paracetamol in rat hepatocytes was studied. Paracetamol was selected as a model-toxin, since it is known to be bioactivated by 3-methylcholanthrene inducible cytochromes P450 presumably to N-acetyl-p-benzoquinone imine (NAPQI), a reactive metabolite which upon overdosage causes protein- and non-protein thiol-depletion, lipid peroxidation and cytotoxicity measured as LDH-leakage. At low concentrations curcumin was found to protect significantly against paracetamol-induced lipid peroxidation, without protection against paracetamol-induced LDH-leakage and without protection against paracetamol-induced GSH-depletion. At a 100 times higher concentration of curcumin the observed protective effect on lipid peroxidation was accompanied with a tendency to increase cellular GSH-depletion and LDH-leakage. No time-dependency was found as to the curcumin-induced effects: treatment of the hepatocytes 1 hr before, concomitantly or 1 hr after the addition of paracetamol to the cells had similar effects. In contrast to what was expected on the basis of previous in vivo experiments, at higher concentrations curcumin itself was found to be slightly cytotoxic. Curcumin-induced LDH-leakage was accompanied by a significant depletion of GSH. It has been concluded that the observed cytoprotective and cytotoxic activities of curcumin may be explained by a strong anti-oxidant capacity of curcumin and the capability of curcumin to conjugate with GSH. Furthermore, it has been concluded that lipid peroxidation is not playing a causal role in cell-death induced by paracetamol or by curcumin.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Donatus IA,Sardjoko,Vermeulen NPdoi
10.1016/0006-2952(90)90603-isubject
Has Abstractpub_date
1990-06-15 00:00:00pages
1869-75issue
12eissn
0006-2952issn
1873-2968pii
0006-2952(90)90603-Ijournal_volume
39pub_type
杂志文章abstract::A strain of hyperlipidaemic Sprague-Dawley (HSD) rat was compared with normal Sprague-Dawley (SD) rats for expression of cholesterol 7alpha-hydroxylase activity (CYP7A1) and other cytochrome P450 (P450) enzymes in liver. Hepatic microsomal CYP7A1 activity in male HSD rats was 2-3-fold lower than in male SD rats with C...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00015-x
更新日期:1998-07-15 00:00:00
abstract::Beta-adrenergic receptors on membranes prepared from rat lung, wild-type S49 lymphoma cells, and the adenylate cyclase-deficient variant of S49 lymphoma cells (cyc-) bind the agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) with high affinity and this binding of [3H]HBI can be inhibited by GTP. Membranes prepared from...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90589-2
更新日期:1987-07-15 00:00:00
abstract::Valine residues in the pore region of SK2 (V366) and SK3 (V520) were replaced by either an alanine or a phenylalanine to evaluate the impact on the interactions with the allosteric blocker apamin. Unlike TEA which showed high sensitivity to phenylalanine mutated channels, the binding affinity of apamin to the phenylal...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.12.015
更新日期:2013-02-15 00:00:00
abstract::The influence of both short- and long-term ethanol exposure on the lipid metabolism was determined in the human hepatoma cell line HepG2. Ethanol did not cause any cytotoxicity or lipid peroxidation even after 7 days of 100 mM ethanol treatment of HepG2 cells. Incubation of cells in the presence of [1-(14)C]ethanol de...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)00896-1
更新日期:2002-04-15 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::Diazepam (DZ), N-desmethyl diazepam (NOR) and temazepam (TEM) were used as substrates in drug metabolism studies to characterize the changes in cytochrome P-450 mono-oxygenase pathways in hepatocytes isolated from cynomolgus monkeys, during culture for 6 days. Hepatocytes were incubated with DZ (20 microM), NOR (6 mic...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90547-9
更新日期:1989-08-15 00:00:00
abstract::The GABA(B) receptor was the first heteromeric G-protein coupled receptor (GPCR) identified. Indeed, both GABA(B1) and GABA(B2) subunits appear necessary to get a functional GABA(B) receptor. Soon after the cloning of both subunits, it was demonstrated that GABA(B2) was required for GABA(B1) to reach the cell surface....
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.06.035
更新日期:2004-10-15 00:00:00
abstract::The ability of adrenergic catechol derivatives, including dobutamine, dopamine, and isoproterenol, to inhibit lipid peroxidation was examined. All the catechol derivatives we tested strongly inhibited lipid peroxidation. Dobutamine was a more powerful inhibitor of iron-catalyzed lipid peroxidation than the other agent...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00075-6
更新日期:1998-06-15 00:00:00
abstract::Incubation of adriamycin resistant Chinese hamster lung cells with the calmodulin inhibitor trifluoperazine (TFP) resulted in a significant increase in the cellular accumulation of drug. When resistant cells were prelabeled with 32Pi and then treated with TFP, a major increase also occurred in the phosphorylation of a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90686-0
更新日期:1985-05-01 00:00:00
abstract::Porcine cerebral microvessels were isolated by differential sieving and centrifugation and were characterized by microscopic examination and marker enzyme enrichment (gamma-glutamyltransferase; EC 2.3.2.2). Purified microvessels contained a membrane-bound enzyme immunologically indistinguishable from renal aminopeptid...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90712-5
更新日期:1988-01-15 00:00:00
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
更新日期:1990-08-01 00:00:00
abstract::The cytotoxic effects of 10 mM acetaminophen (APAP) in primary cultures of non-induced mouse hepatocytes are accompanied by depletion of intracellular glutathione (GSH), arylation of protein, and loss of protein sulfhydryl (PSH) groups. Investigation of the stoichiometry of the covalent binding and PSH loss after APAP...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90686-7
更新日期:1988-09-15 00:00:00
abstract::Son of Sevenless (SOS) was discovered in Drosophila melanogaster. Essential for normal eye development in Drosophila, SOS has two human homologues, SOS1 and SOS2. The SOS1 gene encodes the Son of Sevenless 1 protein, a Ras and Rac guanine nucleotide exchange factor. This protein is composed of several important domain...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2011.07.072
更新日期:2011-11-01 00:00:00
abstract::Antagonists of the chemokine receptor, CCR5, may provide important new drugs for the treatment of HIV-1. In this study we have examined the mechanism of action of two functional antagonists of the chemokine receptor CCR5 (UK-396,794, UK-438,235) in signalling and internalisation assays using CHO cells expressing CCR5....
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.06.032
更新日期:2007-09-15 00:00:00
abstract::Tumor cells proliferate under conditions of oxidative stress. A novel therapeutic approach would be to enhance the cellular effects of the reactive oxygen species formed under these conditions by supplementation with a redox catalyst. This provides a means to target and specifically destroy cancer cells via oxidation ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00544-6
更新日期:2003-11-15 00:00:00
abstract::Energy-dependent drug efflux is a major factor in cellular resistance of P388/R84 mouse leukemic cells to anthracyclines such as doxorubicin (DOX), and blocking of efflux increases sensitivity. However, efflux does not play a significant role in resistance to N-trifluoroacetyladriamycin-14-valerate (AD 32), a DOX anal...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90151-a
更新日期:1990-02-15 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::Spin traps are increasingly employed in the detection of free radicals in biological systems, including liver microsomes and isolated hepatocytes. Two spin traps phenyl-t-butyl nitrone (PBN) and 4-pyridyl-l-oxide-t-butyl nitrone (4-POBN) have been tested for their effects on hepatocyte viability and mixed-function oxi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90010-9
更新日期:1986-11-15 00:00:00
abstract::Membrane damage caused by phospholipase A action is thought to be an important factor in ischemic myocardial injury. Propranolol has been shown previously to have beneficial effects in both animal experiments and clinical trials, and it has membrane-stabilizing properties in vitro. To investigate the possibility that ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90666-6
更新日期:1987-12-15 00:00:00
abstract::The aim of the present study was to investigate the effects of myricitrin, a flavonoid with anti-inflammatory and antinociceptive action, upon persistent neuropathic and inflammatory pain. The neuropathic pain was caused by a partial ligation (2/3) of the sciatic nerve and the inflammatory pain was induced by an intra...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.08.028
更新日期:2006-12-15 00:00:00
abstract::The N,O-sulfate of minoxidil (Mnx) is the active agent in producing the vasodilation and the hair-growth stimulating responses observed with Mnx treatment. In this report, Mnx sulfation activity was assayed in cytosol prepared from several normal human livers, and Mnx sulfation was shown to correlate significantly wit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90489-8
更新日期:1990-09-01 00:00:00
abstract::Nucleoside analogs conjugated with galactosyl-terminating peptides selectively enter liver cells and after intracellular release from the carrier partly exit into bloodstream, resulting in higher concentrations in liver blood than in systemic circulation. The aim of the present experiments was to ascertain whether, in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00561-x
更新日期:2001-02-15 00:00:00
abstract::Gemcitabine (dFdC) is a new cytidine analogue which is active mainly by the incorporation of its triphosphate (dFdCTP) into DNA, leading to cell death. We determined incorporation of dFdC into nucleic acids of two solid tumour cell lines: the murine colon carcinoma cell line Colon 26-10, the human ovarian carcinoma ce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90566-f
更新日期:1993-08-17 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::Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.07.025
更新日期:2015-10-01 00:00:00
abstract::The c-Jun N-terminal kinases (JNKs) exert a pleiotrophy of physiological and pathological actions. This is also true for the immune system. Disruption of the JNK locus results in substantial functional deficits of peripheral T-cells. In contrast to circulating immune cells and the role of p38, the presence and functio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01139-5
更新日期:2002-09-01 00:00:00
abstract::Class B peptide hormone GPCRs are targets for the treatment of major chronic disease. Peptide ligands of these receptors display biased agonism and this may provide future therapeutic advantage. Recent active structures of the calcitonin (CT) and glucagon-like peptide-1 (GLP-1) receptors reveal distinct engagement of ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.02.005
更新日期:2018-04-01 00:00:00
abstract::α6β2-Containing nicotinic acetylcholine receptors (α6β2* nAChRs) are predominantly expressed in midbrain dopaminergic neurons, including substantia nigra pars compacta (SNc) neurons and their projections to striatal regions, where they regulate dopamine release and nigrostriatal activity. It is well established that n...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.113788
更新日期:2020-04-01 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::For several years the IMP/GMP-preferring cytosolic 5'-nucleotidase II (cN-II) has been considered as a therapeutic target in oncology. Indeed, various reports have indicated associations between cN-II expression level and resistance to anticancer agents in several cancer cell lines and in patients affected with neopla...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.01.010
更新日期:2015-03-15 00:00:00