Abstract：
:Tacrolimus (FK506) and cyclosporin A (CsA) are two potent immunosuppressants mainly metabolized by hepatic cytochrome P-450 3A (CYP3A) monooxygenase. The aim of this study was to compare the toxic effects of the two drugs on hepatocytes in primary culture as a function of their metabolism and to explore the variations of cytotoxicity when both drugs are associated. The cytotoxicity of FK506 and CsA, as expressed by their IC50 values, was of the same order but with a switch according to whether hepatocytes were induced or uninduced by dexamethasone, CsA being more toxic in its native form and FK506 through its metabolism. Similar results were obtained with the intracellular calcium content. When both drugs were associated at their IC50 values, the expected additive cytotoxic effect was not observed. Moreover, when small quantities of FK506 were added to CsA at its IC50, cell viability improved in the induced cultures. It is hypothesized that the interaction between the two drugs relies on a mechanism involving both competition of FK506 and CsA for CYP3A and of their immunophilin complexes for a common site on the calcineurin-calmodulin complex.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Ellouk-Achard S,Martin C,Duc HT,Dutertre-Catella H,Thevenin M,Warnet JM,Claude JRdoi
10.1007/s002040050499subject
Has Abstractpub_date
1998-04-01 00:00:00pages
257-63issue
5eissn
0340-5761issn
1432-0738journal_volume
72pub_type
杂志文章abstract：:Berberine, a main protoberberine component of Coptidis Rhizoma, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver. In the preliminary study, berberine expressed an antioxidant property by its capacity for quenching t...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-002-0351-9
更新日期：2002-11-01 00:00:00
abstract：:In anaesthetized and artificially ventilated rabbits an intravenous infusion of paraoxon (0.8 mg/kg) was given over 30 min. The effects on cardiac output, blood flow to various vascular beds, and on the mass discharge of the postganglionic sympathetic efferents to the spleen and kidney were monitored. Immediately foll...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00310857
更新日期：1982-09-01 00:00:00
abstract：:This review provides a compendium of the results of genotoxicity and carcinogenicity assays performed on marketed antihistamines. Of the 70 drugs examined, 29 (41.4%) have at least one genotoxicity and/or carcinogenicity test result: 12 tested positive in at least one genotoxicity assay, six in at least one carcinogen...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-011-0659-4
更新日期：2011-10-01 00:00:00
abstract：:The amphetamine-derived designer drugs have been illegally used worldwide as recreational drugs, some of which are known to be hepatotoxic in humans. To compare their cytotoxic effects, 3,4-methylenedioxy-N-methamphetamine (MDMA) and its related analogues, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-008-0323-9
更新日期：2009-01-01 00:00:00
abstract：:The effects of intravenously (i.v.) administered or inhaled amyl nitrite (AN) were followed under chloralose anaesthesia in intact and cyanide-poisoned, spontaneously breathing beagles. The i.v. doses of AN were 0.03 and 0.15 mmol/kg and the i.v. dose of KCN was 0.06 mmol/kg. AN was inhaled in a closed system at 0.15 ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00570134
更新日期：1988-01-01 00:00:00
abstract：:Oxidative stress is discussed as a possible hepatocarcinogenic mechanism of peroxisome proliferators (PP) in rodents and is suggested to result from the induction of peroxisomal beta-oxidation (PBOX) by PP. The induced PBOX is assumed to produce excessive H2O2 from the degradation of fatty acids, ultimately leading to...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050429
更新日期：1997-01-01 00:00:00
abstract：:Recently, acutely toxic doses of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been reported to affect the hepatic distribution of essential metals in the rat. However, the reduced food intake by TCDD was not taken into account. Therefore, metal concentrations were determined in different...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02284268
更新日期：1991-01-01 00:00:00
abstract：:The goal of these studies was to characterize the role played by antigen challenge in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunosuppression. The effects of single exposure to TCDD (4.2, 14, and 42 microg/kg) in B6C3F1 mice on the reverse plaque assay (RPA; no sensitization) and the sheep red blood cell ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050467
更新日期：1997-01-01 00:00:00
abstract：:Pathological changes induced by cadmium aerosol had features common to the changes evoked by oxidants. Female rats were exposed to fumes of lead, antimony, zinc and cadmium (15-100 nmoles/m3). One hour after termination of exposure, superoxide dismutase (SOD) activity in erythrocytes of the exposed rats lowered by 15-...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00347869
更新日期：1982-03-01 00:00:00
abstract：:Chronic ciprofibrate administration resulted in distinct differences in hepatic responses between the two species examined. In the rat, hepatomegaly was observed with the coordinate induction of carnitine acetyltransferase, peroxisomal beta-oxidation and cytochrome P450IVA1 activities. The latter induction of cytochro...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02034935
更新日期：1991-01-01 00:00:00
abstract：:Occupational and environmental asbestos exposure is the main determinant of malignant pleural mesothelioma (MPM), however, the mechanisms by which its fibres contribute to cell toxicity and transformation are not completely clear. Aberrant DNA methylation is a common event in cancer but epigenetic modifications involv...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-018-2179-y
更新日期：2018-05-01 00:00:00
abstract：:Di(2-ethylhexyl)phthalate (DEHP) and mono-(2-ethylhexyl)phthalate (MEHP) were administered PO or IP to pregnant ICR mice at varying doses on days 7, 8, and 9 of gestation. In groups given DEHP orally, resorptions and malformed fetuses increased significantly at 1,000 mg/kg. Fetal weights were also significantly suppre...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00295165
更新日期：1985-02-01 00:00:00
abstract：:The effect of pretreatment with cadmium (Cd) complexes on the distribution and accumulation of Cd in the liver and kidneys was examined for the Cd complexes that are reabsorbed site-selectively at the renal proximal tubules of rats. Cd was administered simultaneously with excess cysteine or as metallothionein (MT) and...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00297117
更新日期：1986-04-01 00:00:00
abstract：:The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity induced by acute exposure to cadmium-metallothionein (Cd-MT) in rats was studied. Rats were injected intraperitoneally with BGD (400 mumol/kg) 6, 12, or 24 h after intraperitoneal injection of Cd-MT (1.78 mumol Cd as Cd-MT/kg) and thereafte...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01974392
更新日期：1990-01-01 00:00:00
abstract：:The organophosphorus compound trichlorfon, dimethyl (2,2,2-trichloro-1-hydroxyethyl) phosphonate, was administered by stomach tube (100 mg/kg) to pregnant guinea pigs at two different stages of gestation (days 36, 37, 38 and 51, 52, 53). The pups developed locomotory disturbances, and post mortem examination revealed ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00263954
更新日期：1986-05-01 00:00:00
abstract：:The kinetics of vitamin E was followed in serum, liver and kidney of 10- and 55-day-old rats after the administration of a single i.m. dose of 100 mg alpha-tocopherol acetate/100 g body wt. The basal levels without vitamin E administration were significantly higher in serum and liver of 10- than 55-day-old rats. The e...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050444
更新日期：1997-01-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) is known to mediate the cellular response to numerous xenobiotics including dioxin. Surprisingly AHR knockout mice provide evidence for the involvement of the AHR signalling cascade in estrogen regulated physiological functions of the female reproductive system. Several studies alre...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-012-0870-y
更新日期：2012-10-01 00:00:00
abstract：:Doppler and M-mode echocardiography (EC) were used to investigate the effects of minoxidil on the cardiac function of the dog and potentially to clarify the pathogenesis of cardiac lesions, in particular the necrotic lesion in the left ventricle and the haemorrhagic lesion in the right atrium. Groups of three dogs wer...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0503-6
更新日期：2004-01-01 00:00:00
abstract：:The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17beta-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomi...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-008-0288-8
更新日期：2008-10-01 00:00:00
abstract：:A study was conducted to determine the levels of cis-diamminedichloroplatinum (II) (cisplatin) in plasma proteins and hemoglobin of cancer patients after cisplatin chemotherapy. Thirty-seven cancer patients with different type of cancers (lung, esophageal, urinary tract, and testicular cancer, melanoma, osteosarcoma e...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00303124
更新日期：1989-01-01 00:00:00
abstract：:Unsaturated compounds are known to cause false-positive reactions in the local lymph node assay (LLNA) but not in the guinea pig maximization test. We have tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol, fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid, squalene, ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-015-1527-4
更新日期：2016-04-01 00:00:00
abstract：:A method is outlined to estimate from hemodialysis or hemoperfusion data, respectively, the rate constants, the distribution volume in the beta-phase, and other pharmacokinetic parameters of toxic substances. All calculations are based on the assumption that the usual linear open two-compartment system is also the app...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01459998
更新日期：1983-05-01 00:00:00
abstract：:Female Wistar rats were treated with various doses of progesterone orally via the diet or via the SC route. Oral treatment resulted in enhanced progesterone levels in the liver as measured by radioimmunoassay. There were up to 3-fold increases in activity of ethylmorphine demethylation by isolated microsomes; metaboli...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00316323
更新日期：1986-10-01 00:00:00
abstract：:Since teratogenicity testing in mammals is a particular challenge from an animal welfare perspective, there is a great need for the development of alternative test systems. In this context, the zebrafish (Danio rerio) embryo has received increasing attention as a non-protected embryonic vertebrate in vivo model. The p...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-020-02928-7
更新日期：2020-10-27 00:00:00
abstract：:The effect of lindane and heptachlor on haem metabolism was studied with the aim to elucidate the mechanism of their porphyrinogenic action. The effects of these compounds on delta-aminolaevulinate synthase (ALA-S) and ferrochelatase were evaluated and the mechanism of increase of ALA-S activity was especially studied...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050566
更新日期：1998-11-01 00:00:00
abstract：:Volunteers inhaled a constant concentration of 50 ppm trichloroethylene (Tri) for 6 hrs per day on 5 consecutive days. Simultaneous ethanol (EtOH) ingestion (blood level 0.6%) inhibits the metabolization of Tri to trichloroethanol (TCE) and trichloroacetic acid (TCA) by 40% on the average. Oxidation of Tri to TCA does...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00311271
更新日期：1975-01-01 00:00:00
abstract：:Cadmium-induced metallothionein (MT) synthesis was investigated in male rats of three ages, 3, 12 and 24 months. Physiological levels of MT in kidney, liver and lung measured simultaneously in untreated animals were found to be within the same range in all three age groups. Following 3-day treatment with CdCl2 equival...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00293629
更新日期：1988-01-01 00:00:00
abstract：:In female rats, the lethality and hepatotoxicity of cerous chloride (CeCl3) were significantly altered by pretreatment with steroidal and nonsteroidal compounds (pregnenolone-16alpha-carbonitrile "PCN", dexamethasone, spironolactone, phenobarbital) that stimulate hepatic drug-metabolizine enzyme activity and by estrad...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00372765
更新日期：1976-03-11 00:00:00
abstract：:Perfluoroalkyl acids are widely used in numerous industrial and commercial applications due to their unique physical and chemical characteristics. Although perfluorooctanoic acid (PFOA) is associated with hepatomegaly through peroxisome proliferator-activated receptor α (PPARα) activation, liver fat accumulation and c...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1322-7
更新日期：2015-09-01 00:00:00
abstract：:The development of metabolically competent in vitro models is of utmost importance for predicting adverse drug reactions, thereby preventing attrition-related economical and clinical burdens. Using the antiretroviral drug nevirapine (NVP) as a model, this work aimed to validate rat hepatocyte 3D spheroid cultures as c...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1792-x
更新日期：2017-03-01 00:00:00
