当前位置： SCI文献检索 > ARCHIVES OF TOXICOLOGY期刊下所有文献 > Cytotoxic effects of 3,4-methylenedioxy-N-alkylamphetamines, MDMA and its analogues, on isolated rat hepatocytes.

Cytotoxic effects of 3,4-methylenedioxy-N-alkylamphetamines, MDMA and its analogues, on isolated rat hepatocytes.

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-(methylenedioxyphenyl)-2-butanamine (BDB) and 2-methylamino-1-(3,4-methylenedioxyphenyl)-propane-1-one (methylone) were studied in freshly isolated rat hepatocytes. MBDB caused not only concentration (0-4.0 mM)- and time (0-2 h)-dependent cell death accompanied by the formation of cell blebs, and the loss of cellular ATP and adenine nucleotide pools, and reduced glutathione levels, but also the accumulation of oxidized glutathione. Of the other analogues examined, the cytotoxicity of MBDB and BDB was greater than that of MDMA and methylone, suggesting that hepatotoxicity is generally induced by these drugs. In addition, DNA damage and the induction of reactive oxygen species were greater after the incubation of hepatocytes with MBDB (2 and 4 mM) than after that with MDMA. In isolated liver mitochondria, MBDB/BDB resulted in a greater increase in the rate of state 4 oxygen consumption than did MDMA/methylone, indicating an uncoupling effect and a decrease in the rate of state 3 oxygen consumption in a concentration dependent manner. Furthermore, MBDB resulted in mitochondrial swelling dependent on the mitochondrial permeability transition (MPT); the effect of MDMA was less than that of MBDB. Taken collectively, these results suggest that (1) the onset of cytotoxicity caused by designer drugs such as MBDB and MDMA is linked to mitochondrial failure dependent upon the induction of the MPT accompanied by mitochondrial depolarization and depletion of ATP through uncoupling of oxidative phosphorylation in rat hepatocytes, and (2) MBDB and MDMA elicit DNA damage, suggesting that nuclei as well as mitochondria are target sites of these compounds.

journal_name

Arch Toxicol

journal_title

Archives of toxicology

authors

Nakagawa Y,Suzuki T,Tayama S,Ishii H,Ogata A

doi

10.1007/s00204-008-0323-9

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

69-80

issue

1

eissn

0340-5761

issn

1432-0738

journal_volume

83

pub_type

杂志文章

相关文献

ARCHIVES OF TOXICOLOGY文献大全
  • Cadmium chloride inhibits lactate gluconeogenesis in isolated human renal proximal tubules: a cellular metabolomic approach with 13C-NMR.

    abstract：:As part of a study on cadmium nephrotoxicity, we studied the effect of cadmium chloride (CdCl2) in isolated human renal proximal tubules metabolizing the physiological substrate lactate. Dose-effect experiments showed that 10-500 μM CdCl2 reduced lactate removal, glucose production and the cellular levels of ATP, coen...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-010-0633-6

    authors： Faiz H,Conjard-Duplany A,Boghossian M,Martin G,Baverel G,Ferrier B

    更新日期：2011-09-01 00:00:00

  • Toxicity of PCB-126 in European flounder (Platichthys flesus) with emphasis on histopathology and cytochrome P4501A induction in several organ systems.

    abstract：:A series of experiments was set up to elucidate the effects of pollution on marine and estuarine fish health, since the European flounder (Platichthys flesus) has shown a relatively high prevalence of (pre)neoplastic liver lesions and lymphocystis virus disease in Dutch coastal and estuarine waters. The hypothesis of ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040100213

    authors： Grinwis GC,van den Brandhof EJ,Engelsma MY,Kuiper RV,Vaal MA,Vethaak AD,Wester PW,Vos JG

    更新日期：2001-04-01 00:00:00

  • Genotype and allele frequencies of polymorphic CYP2E1 in the Turkish population.

    abstract：:Cytochrome P4502E1 (CYP2E1) gene shows genetic polymorphisms that vary markedly in frequency among different ethnic and racial groups. We studied the genotype distributions and allele frequencies of three CYP2E1 polymorphisms: CYP2E1*5B (RsaI/PstI RFLP, C-1053T/G-1293C SNP, rs2031920 /rs3813867), CYP2E1*6 (DraI RFLP, ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-007-0200-y

    authors： Ulusoy G,Arinç E,Adali O

    更新日期：2007-10-01 00:00:00

  • Identification and determination of 2-thiothiazolidine-4-carboxylic acid in urine of workers exposed to carbon disulfide.

    abstract：:A compound was isolated from the urine of workers exposed to carbon disulfide during the production of rayon. The compound was identified as 2-thiothiazolidine-4-carboxylic acid (TTCA) by GC/MS and NMR. A HPLC method for the quantitative determination of TTCA was elaborated and applied to urine samples. The method all...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00297130

    authors： van Doorn R,Delbressine LP,Leijdekkers CM,Vertin PG,Henderson PT

    更新日期：1981-03-01 00:00:00

  • Deficit in learning and memory of rats with chronic fluorosis correlates with the decreased expressions of M1 and M3 muscarinic acetylcholine receptors.

    abstract：:To reveal the molecular mechanism of deficit in learning and memory induced by chronic fluorosis, the expression of muscarinic acetylcholine receptors (mAChRs) and oxidative stress were investigated. Sixty Sprague-Dawley (SD) rats were divided randomly into two groups (30 cases in each), i.e., the control group (<0.5 ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-014-1408-2

    authors： Dong YT,Wang Y,Wei N,Zhang QF,Guan ZZ

    更新日期：2015-11-01 00:00:00

  • Hematological toxicity of tetrachloroethylene in mice.

    abstract：:Female C57/BL/6 x DBA/2 hybrid mice were exposed to two concentrations (270 and 135 ppm) of tetrachloroethylene (PER) in inhalation chambers for 6 h/day, 5 days per week, up to 11.5 weeks (270 ppm) and 7.5 weeks (135 ppm), respectively, followed by a 3-week exposure-free period. In the peripheral blood a reduction of ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF01974021

    authors： Seidel HJ,Weber L,Barthel E

    更新日期：1992-01-01 00:00:00

  • Evaluation of methylmercury biotransformation using rat liver slices.

    abstract：:To examine the demethylation reaction of methylmercury (MeHg) in rat liver, slices prepared from MeHg-treated rats were incubated in L-15 medium under 95% O2/5% CO2 atmosphere. During the incubation, the amount of inorganic Hg in the slices markedly increased in a time-dependent manner, although the concentration of t...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040100256

    authors： Yasutake A,Hirayama K

    更新日期：2001-09-01 00:00:00

  • A review of species differences in the control of, and response to, chemical-induced thyroid hormone perturbations leading to thyroid cancer.

    abstract：:This review summarises the current state of knowledge regarding the physiology and control of production of thyroid hormones, the effects of chemicals in perturbing their synthesis and release that result in thyroid cancer. It does not consider the potential neurodevelopmental consequences of low thyroid hormones. The...

    journal_title：Archives of toxicology

    pub_type： 杂志文章,评审

    doi：10.1007/s00204-020-02961-6

    authors： Foster JR,Tinwell H,Melching-Kollmuss S

    更新日期：2021-01-05 00:00:00

  • Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days.

    abstract：:Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and function of hPCLS to 5 d...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-016-1865-x

    authors： Starokozhko V,Vatakuti S,Schievink B,Merema MT,Asplund A,Synnergren J,Aspegren A,Groothuis GMM

    更新日期：2017-05-01 00:00:00

  • The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain.

    abstract：:The present study was designed to evaluate the effects of chronic fluorosis on the dynamics (including fusion and fission proteins), fragmentation, and distribution of mitochondria in the cortical neurons of the rat brain in an attempt to elucidate molecular mechanisms underlying the brain damage associated with exces...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-012-0942-z

    authors： Lou DD,Guan ZZ,Liu YJ,Liu YF,Zhang KL,Pan JG,Pei JJ

    更新日期：2013-03-01 00:00:00

  • Trenbolone growth promotant: covalent DNA binding in rat liver and in Salmonella typhimurium, and mutagenicity in the Ames test.

    abstract：:DNA binding in vivo: [6,7-3H]beta-trenbolone (beta-TBOH) was administered p.o. and i.p. to rats. After 8 or 16 h, DNA was isolated from the livers and purified to constant specific radioactivity. Enzymatic digestion to deoxyribonucleotides and separation by HPLC revealed about 90% of the DNA radioactivity eluting in t...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00570127

    authors： Lutz WK,Deuber R,Caviezel M,Sagelsdorff P,Friederich U,Schlatter C

    更新日期：1988-01-01 00:00:00

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition.

    abstract：:Contents of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of 16 further congeners--polychlorinated dibenzodioxins and dibenzofuranes (PCDD/PCDF)--were determined in lipids of adipose tissue and of livers of 3 stillborns and of 17 infants (0.43-44 weeks old) who died from sudden infant death syndrome. International to...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040050402

    authors： Kreuzer PE,Csanády GA,Baur C,Kessler W,Päpke O,Greim H,Filser JG

    更新日期：1997-01-01 00:00:00

  • Changes in markers of oxidative status in brain, liver and kidney of young and aged rats following exposure to aromatic white spirit.

    abstract：:Levels of glutathione and activity of glutamine synthetase were assayed in organs of rats following inhalation of a heterogeneous solvent mixture containing both aliphatic and aromatic hydrocarbons. This mixture was administered for 3 weeks (6 h daily) at two levels in the inhaled air (400 and 800 ppm) to young adult ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s002040050192

    authors： Bondy SC,Lam HR,Ostergaard G,Guo SX,Ladefoged O

    更新日期：1995-01-01 00:00:00

  • Determination of lorazepam in plasma by electron capture GLC.

    abstract：:A method is described for the determination of lorazepam plasma levels involving extraction from the sample and analysis of the intact lorazepam by electron capture gas-liquid chromatography. Using mass spectrometry it is demonstrated, that lorazepam shows a thermal rearrangement under gas chromatographic conditions. ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00293571

    authors： de Groot G,Maes RA,Lemmens HH

    更新日期：1976-06-08 00:00:00

  • Dual effect of red wine on liver redox status: a concise and mechanistic review.

    abstract：:Chronic ethanol consumption is a strong risk factor for the development of liver disease. Multiple mechanisms are involved in ethanol-mediated liver injury; oxidative stress being pointed has an important factor. However, it should be noted that moderate consumption of red wine has been associated with hepatoprotectiv...

    journal_title：Archives of toxicology

    pub_type： 杂志文章,评审

    doi：10.1007/s00204-015-1538-1

    authors： Silva P,Fernandes E,Carvalho F

    更新日期：2015-10-01 00:00:00

  • Activity of O6-methylguanine DNA methyltransferase in mononuclear blood cells of formaldehyde-exposed medical students.

    abstract：:A recent study reported that exposure of student embalmers in Cincinnati to high concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair enzyme may strongly increase the cancer risk not only with respect to the rep...

    journal_title：Archives of toxicology

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1007/s002040050581

    authors： Schlink K,Janssen K,Nitzsche S,Gebhard S,Hengstler JG,Klein S,Oesch F

    更新日期：1999-02-01 00:00:00

  • VEGF isoforms and receptors expression throughout acute acetaminophen-induced liver injury and regeneration.

    abstract：:Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent. Vascular endothelial growth factor (VEGF) is a growth factor with multiple functional roles. VEGF plays an important role in angiogenesis and hepatic regeneration. The aim of this study was to determine the expression of VEGF isoforms and i...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-007-0201-x

    authors： Papastefanou VP,Bozas E,Mykoniatis MG,Grypioti A,Garyfallidis S,Bartsocas CS,Nicolopoulou-Stamati P

    更新日期：2007-10-01 00:00:00

  • Inhibition of poly(ADP-ribose) polymerase (PARP) influences the mode of sulfur mustard (SM)-induced cell death in HaCaT cells.

    abstract：:Sulfur mustard (SM) is a bifunctional alkylating agent. Its primary toxic consequence is severe skin damage with blisters, occurring after skin contact. These vesicant properties of SM have been linked to cell death of proliferating keratinocytes in the basal layer of the skin. Catalytic activation of the nuclear enzy...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-007-0265-7

    authors： Kehe K,Raithel K,Kreppel H,Jochum M,Worek F,Thiermann H

    更新日期：2008-07-01 00:00:00

  • Identification of the human liver UDP-glucuronosyltransferase involved in the metabolism of p-ethoxyphenylurea (dulcin).

    abstract：:Dulcin (DL), now banned, was once a widely used artificial sweetener. DL possesses an ureido group that is metabolized by direct glucuronidation in rabbit liver microsomes. Dulcin N-glucuronide (DNG) is the only type of ureido N-glucuronide known to date; ureido glucuronidation in humans has not been previously report...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-006-0138-5

    authors： Uesawa Y,Staines AG,Lockley D,Mohri K,Burchell B

    更新日期：2007-03-01 00:00:00

  • Influence of arsenate and arsenite on signal transduction pathways: an update.

    abstract：:Arsenic has been a recognized contaminant and toxicant, as well as a medicinal compound throughout human history. Populations throughout the world are exposed to arsenic and these exposures have been associated with a number of human cancers. Not much is known about the role of arsenic as a human carcinogen and more r...

    journal_title：Archives of toxicology

    pub_type： 杂志文章,评审

    doi：10.1007/s00204-010-0554-4

    authors： Druwe IL,Vaillancourt RR

    更新日期：2010-08-01 00:00:00

  • Comparative hepatotoxicity and metabolism of N-methylformamide in rats and mice.

    abstract：:N-methylformamide (NMF) produced dose-dependent zone 3 haemorrhagic necrosis in mice; the threshold dose was 100-200 mg/kg. In rats a dose of 1000 mg/kg caused hepatic damage in some animals and slight elevations of plasma transaminases. A species difference in susceptibility to NMF-induced hepatotoxicity is clearly i...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00570135

    authors： Tulip K,Timbrell JA

    更新日期：1988-01-01 00:00:00

  • Effects of calcium channel blockers on the development of early rat postimplantation embryos in culture.

    abstract：:Rat embryos (9.5-day-old) were cultured for 48 h in the presence of nifedipine (NIF), nimodipine (NIM), nitrendipine (NIT), gallopamil HCl (GAL), verapamil HCl (VER) and diltiazem HCl (DIL). The effects on growth and morphogenetic differentiation in vitro were monitored. Dose-response relationships were evaluated, inc...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF01974690

    authors： Stein G,Srivastava MK,Merker HJ,Neubert D

    更新日期：1990-01-01 00:00:00

  • Peripheral neuropathy following intraneural injection of mercury compounds.

    abstract：:Between 0.25-25 micrograms of an aqueous solution of either mercuric chloride or methyl mercuric acetate was injected directly into the sciatic nerve of 28 adult Wistar rats. The resultant pathological changes in the nerve were examined by teasing individual fibres and by light and electron microscopy. In most respect...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00310442

    authors： Mitchell J,Gallagher PJ

    更新日期：1980-12-01 00:00:00

  • Antibiotic resistance mechanisms in M. tuberculosis: an update.

    abstract：:Treatment of tuberculosis (TB) has been a therapeutic challenge because of not only the naturally high resistance level of Mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. Currently standardized regimens require patients to daily ingest up to four drugs un...

    journal_title：Archives of toxicology

    pub_type： 杂志文章,评审

    doi：10.1007/s00204-016-1727-6

    authors： Nguyen L

    更新日期：2016-07-01 00:00:00

  • Ochratoxin A induces epithelial-to-mesenchymal transition and renal fibrosis through TGF-β/Smad2/3 and Wnt1/β-catenin signaling pathways in vitro and in vivo.

    abstract：:Ochratoxin A (OTA) is a toxin produced by fungi such as Aspergillus spp. and Penicillium spp. The key target organ of OTA toxicity is the kidney, and it is known that epithelial-to-mesenchymal transition (EMT) leading to fibrosis is enhanced after long-term exposure of the kidney to OTA. However, the mechanisms respon...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-020-02829-9

    authors： Pyo MC,Chae SA,Yoo HJ,Lee KW

    更新日期：2020-09-01 00:00:00

  • Histological examination of the rat after long-term exposure to subtoxic automotive exhaust gas.

    abstract：:Regarding the potential impact of traffic-born air pollutants on public health, in recent years attention has increasingly been focused on the possible effects on the cardiovascular system. In order to investigate this problem further, the influence of long-term exhaust gas exposure on rats has been studied. One hundr...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00332390

    authors： Roggendorf W,Neumann H,Thron HL,Schneider H,Sarasa-Corral JL

    更新日期：1981-07-01 00:00:00

  • Regional alterations of brain catecholamines by styrene exposure in rabbits.

    abstract：:The regional distribution of dopamine, norepinephrine and homovanillic acid was assessed in adult male rabbits exposed to styrene vapours. The turnover of dopamine and norepinephrine was also measured in several brain regions by the decay in endogenous catecholamines after inhibition of tyrosine hydroxylase by alpha-m...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/BF00316123

    authors： Mutti A,Falzoi M,Romanelli A,Franchini I

    更新日期：1984-09-01 00:00:00

  • Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey.

    abstract：:Boric acid and sodium borates are currently classified as being toxic to reproduction under "Category 1B" with the hazard statement of "H360 FD" in the European CLP regulation. This has prompted studies on boron-mediated reprotoxic effects in male workers in boron mining areas and boric acid production plants. By cont...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-018-2238-4

    authors： Duydu Y,Başaran N,Üstündağ A,Aydın S,Yalçın CÖ,Anlar HG,Bacanlı M,Aydos K,Atabekoğlu CS,Golka K,Ickstadt K,Schwerdtle T,Werner M,Meyer S,Bolt HM

    更新日期：2018-08-01 00:00:00

  • SEURAT: Safety Evaluation Ultimately Replacing Animal Testing--recommendations for future research in the field of predictive toxicology.

    abstract：:The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained ...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-014-1421-5

    authors： Daston G,Knight DJ,Schwarz M,Gocht T,Thomas RS,Mahony C,Whelan M

    更新日期：2015-01-01 00:00:00

  • Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells.

    abstract：:In case of mycotoxin contaminations, food and feedstuff are usually contaminated by more than one toxin. However toxicological data concerning the effects of mycotoxin combinations are sparse. The intestinal epithelium is the first barrier against food contaminants and this constantly renewing organ is particularly se...

    journal_title：Archives of toxicology

    pub_type： 杂志文章

    doi：10.1007/s00204-014-1309-4

    authors： Alassane-Kpembi I,Puel O,Oswald IP

    更新日期：2015-08-01 00:00:00