Abstract:
:The effect of a choline-deficient diet on microsomal cytochrome P-450 and mixed-function oxidase (MFO) activity was investigated in relation to the development of nutritional cirrhosis. In rats that received the choline-deficient diet for 28 weeks cirrhosis was evident macroscopically and histologically; control rats that received an identical diet supplemented with choline had normal livers. Microsomal cytochrome P-450 and cytochrome b5 were reduced in cirrhotic liver to 50% of control levels. Three MFO activities (ethylmorphine N-demethylase, aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase) were also reduced to 40-70% of control levels. However, the turnover number for the O-deethylation of 7-ethoxycoumarin was not reduced in cirrhotic liver. This finding suggested that certain drug oxidations may be selectively depressed in nutritional cirrhosis. To examine the possibility that selective changes in MFO activity may reflect the suppression of certain cytochrome P-450 isozymes, partially purified fractions of the cytochrome were prepared after solubilisation and hydrophobic affinity chromatography (on n-octylamino-Sepharose 4B) of cirrhotic and control liver microsomes. Analysis of these fractions by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and laser densitometry indicated that a protein band of apparent minimum molecular weight 50.5 kD was primarily affected in cirrhotic rat liver microsomes. Levels of two other bands (apparent minimum molecular weight 48 and 52.5 kD) appeared essentially unaltered. Additional electrophoretic studies, conducted under non-reduced conditions, indicated the haemoprotein nature of protein bands in the 48-55 kD region. These data strongly suggest that cirrhosis produced in rats by a choline-deficient diet is associated with selective decreases in oxidative drug metabolism and individual cytochrome P-450 isozymes.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Murray M,Zaluzny L,Farrell GCdoi
10.1016/0006-2952(86)90298-4subject
Has Abstractpub_date
1986-06-01 00:00:00pages
1817-24issue
11eissn
0006-2952issn
1873-2968pii
0006-2952(86)90298-4journal_volume
35pub_type
杂志文章abstract::We have recently identified hyperforin, a lipophilic constituent of the herb Hypericum perforatum (St. John's wort), as a dual inhibitor of the proinflammatory enzymes cyclooxygenase-1 and 5-lipoxygenase. The aim of the present study was to further elucidate antiinflammatory properties and respective targets of hyperf...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2003.12.020
更新日期:2004-04-15 00:00:00
abstract::We examined the effects of the gastrin family of peptides on gastric mucus glycoprotein (mucin) biosynthesis in rat gastric mucosa using an organ culture technique. Radiolabeled mucin was obtained from the tissue and culture medium of the corpus and antrum of rat stomach incubated for 5 hr with [3H]glucosamine (GlcN),...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90322-n
更新日期:1993-11-02 00:00:00
abstract::The effects of two recently developed alpha 2-adrenergic antagonists, RX 781094 and WY 26703, on the synthesis of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in rat brain were compared to those of yohimbine, its diastereoisomer rauwolscine, and mianserin. Intraperitoneal administration of these compounds i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90614-8
更新日期:1985-04-01 00:00:00
abstract::5-Hydroxytryptamine (serotonin, 5-HT) stimulates basal adenylyl cyclase activity in membranes from guinea pig or rat hippocampi, but 5-HT inhibits forskolin-stimulated adenylyl cyclase activity in these same membranes. The opposing effects of 5-HT on adenylyl cyclase activity indicate that distinct 5-HT receptors, pos...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90453-r
更新日期:1990-10-01 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::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
doi:10.1016/j.bcp.2014.02.025
更新日期:2014-05-15 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::A structure-activity study of fourteen chemically related flavonoids was conducted to evaluate their abilities to inhibit glutathione reductase (GR). By comparing the I50 values of flavonoids from different classes possessing an identical hydroxyl configuration, we determined the following order of potency for inhibit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90478-2
更新日期:1992-10-20 00:00:00
abstract::Heme oxygenase 1 (HO-1) is a stress protein and has been suggested to provide defense mechanisms against agents that may induce oxidative injury. Vitamin E (VE) is considered to function as an important cellular antioxidant. Rats were fed a VE-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then were intr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00302-x
更新日期:1997-11-15 00:00:00
abstract::Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases f...
journal_title:Biochemical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0006-2952(98)00372-4
更新日期:1999-04-15 00:00:00
abstract::The effects of schisanhenol (Sal) on Adriamycin (ADM)-induced rat heart mitochondrial toxicity in vitro were investigated. Malondialdehyde formation, lysis, disintegration and membrane rigidification in mitochondria treated with ADM were reduced significantly by Sal. In the electron spin resonance studies, Sal did not...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90519-b
更新日期:1991-10-09 00:00:00
abstract::Diisopropyl-1,3-dithiol-2-ylidenemalonate (malotilate) was studied for and compared with cyanidanol, hydrocortisone and colchicin on its impact on fibroblast cultures. Under in vitro conditions, malotilate specifically reduces collagen synthesis of fibroblasts. In addition, malotilate is an efficient inhibitor of fibr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90464-3
更新日期:1987-11-15 00:00:00
abstract::Sublines of K562 human leukemia cells were selected for resistance (30- to 80-fold) to etoposide by continuous exposure to 0.5 microM VP-16. Two etoposide-resistant cell lines, K/VP.5 and K/VP.5-1, showed a 5-fold reduction in levels of topoisomerase II alpha protein compared with K562 cells. Northern analysis indicat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90643-b
更新日期:1993-12-03 00:00:00
abstract::In advanced stages of cancer disease, caveolin-1 (CAV1) expression increases and correlates with increased migratory and invasive capacity of the respective tumor cells. Previous findings from our laboratory revealed that specific ECM-integrin interactions and tyrosine-14 phosphorylation of CAV1 are required for CAV1-...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.113941
更新日期:2020-07-01 00:00:00
abstract::Three sulfolipid compounds, 1, 2, and 3, have been isolated from a higher plant, a pteridophyte, Athyrium niponicum, as potent inhibitors of the activities of calf DNA polymerase alpha and rat DNA polymerase beta. The inhibition by the sulfolipids was concentration dependent, and almost complete inhibition of DNA poly...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00536-4
更新日期:1998-02-15 00:00:00
abstract::Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to the lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,收录出版
doi:10.1016/j.bcp.2010.06.022
更新日期:2010-10-01 00:00:00
abstract::Polyphenolic anthocyanins are major colorful compounds in red fruits, known to prevent cardiovascular and other diseases. Grape polyphenols are a mixture of various molecules and their exact contribution to above bioactivities remains to be clarified. In the present study, we first analyzed the effect of purified grap...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.06.010
更新日期:2013-11-15 00:00:00
abstract::The influence of various concentrations of ferrous iron and ascorbate on in vitro peroxidation and drug binding of diverse membrane preparations (cerebral cortex and liver) was studied. Peroxidation was not simply dose-related to ascorbate and ferrous iron, but a complex relationship between iron and ascorbate when ad...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02058-6
更新日期:1995-11-27 00:00:00
abstract::The hypolipidemic drug ethyl chlorophenoxyisobutyrate (clofibrate) is known to induce peroxisome proliferation and to be carcinogenic after long term administration to rats and mice. We examined the effects of treatment with this drug for periods of up to 18 months on cytosolic ATP-stimulated and ADP-inhibited acetyl-...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90038-x
更新日期:1993-04-06 00:00:00
abstract::We have shown previously that Z-1,1-dichloro-2,3-diphenylcyclopropane (a.k.a. Analog II, A(II)) inhibits human breast cancer cell proliferation regardless of estrogen receptor status or estrogen sensitivity, and that its cellular targets include microtubules. In the present study, we investigated the apoptosis-inducin...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00289-5
更新日期:1999-01-01 00:00:00
abstract::Tanshinone I (Tanshinone-1), a major active principle of the traditional Chinese medicine Salvia miltiorrhiza, possesses excellent anticancer properties, including inhibiting proliferation, angiogenesis and metastasis and overcoming multidrug resistance (MDR). However, its direct anticancer molecular target(s) remain ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.05.006
更新日期:2018-08-01 00:00:00
abstract::Lactate, once considered a metabolic dead-end, has been recently proposed to support neuron bioenergetics. To better understand how lactate specifically influences cell energy metabolism, we studied the effects of lactate supplementation on SH-SY5Y human neuroblastoma cell bioenergetic fluxes. Lactate supplementation ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.11.002
更新日期:2016-01-01 00:00:00
abstract::Intact, biological active insulin and pancreatic RNase can be absorbed from the intestinal lumen into the blood circulation. The absorption is dependent on the addition of bile acid (sodium cholate) and proteinase inhibitor. The quantitative absorption of insulin and pancreatic RNase has been demonstrated in an in sit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90411-4
更新日期:1987-04-01 00:00:00
abstract::The response and engagement of host normal tissues in malignant disease are major factors in therapeutic resistance. Physically, solid tumors have regions of hypoxia and acidosis. These physical stresses can lead to a more aggressive malignant phenotype through activation of HIF, GLUT-1, carbonic anhydrase IX, and sub...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2009.01.006
更新日期:2009-06-01 00:00:00
abstract::The effects of ticlopidine and six of its analogues on mitochondrial functions were studied in isolated rat liver mitochondria. The influence of ticlopidine and each of the following analogues: PCR 5325, PCR 4099, PCR 3787, PCR 2362, PCR 4499 and PCR 0665 was evaluated by determining their interaction with three major...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90057-1
更新日期:1984-12-01 00:00:00
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
doi:10.1016/0006-2952(87)90549-1
更新日期:1987-08-15 00:00:00
abstract::Originally discovered as an anti-fungal agent, the bacterial macrolide rapamycin is a potent immunosuppressant and a promising anti-cancer drug. In complex with its cellular receptor, the FK506-binding protein (FKBP12), rapamycin binds and inhibits the function of the mammalian target of rapamycin (mTOR). By mediating...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(02)01263-7
更新日期:2002-10-01 00:00:00
abstract::Phomopsins comprise a family of peptide mycotoxins containing a 13-membered ring formed by an ether bridge, produced by the fungus Phomopsis leptostromiformis, the causal agent in lupin poisoning (lupinosis). The biochemical actions of two naturally occurring phomopsins, phomopsin A and B, and the chemical derivatives...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90141-9
更新日期:1987-07-01 00:00:00
abstract::Carbon tetrachloride (CCl4)-induced inhibition of very low density lipoprotein (VLDL) secretion was studied in isolated hepatocytes. The hypothesis that inhibition of secretion is due to altered calcium homeostasis following CCl4-dependent inhibition of endoplasmic reticulum calcium sequestration was investigated. Inh...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90714-7
更新日期:1984-08-01 00:00:00
abstract::Lesions to DNA trigger the DNA-damage response (DDR), a complex, multi-branched cell-intrinsic process targeted to DNA repair, or elimination of the damaged cells by apoptosis. DDR aims at reducing permanence of mutated cells, decreasing the risk of tumor development: the more stringent the response, the lower the lik...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2012.07.022
更新日期:2012-11-15 00:00:00