Abstract:
:In the clinical setting, antidotes are generally administered after the occurrence of a drug overdose. Therefore, the most pertinent evaluation of any new agent should model human exposure. This study tested whether acetaminophen (APAP) hepatotoxicity was reversed when S-adenosyl-L-methionine (SAMe) was administered after APAP exposure, similar to what occurs in clinical situations. Comparisons were made for potency between SAMe and N-acetylcysteine (NAC), the current treatment for APAP toxicity. Male C57BL/6 mice were fasted overnight and divided into groups: control (VEH), SAMe treated (SAMe), APAP treated (APAP), N-acetylcysteine treated (NAC), SAMe or NAC administered 1h after APAP (SAMe+APAP) and (NAC+APAP), respectively. Mice were injected intraperitoneal (i.p.) with water (VEH) or 250 mg/kg APAP (15 ml/kg). One hour later, mice were injected (i.p.) with 1.25 mmol/kg SAMe (SAMe+APAP) or NAC (NAC+APAP). Hepatotoxicity was evaluated 4h after APAP or VEH treatment. APAP induced centrilobular necrosis, increased liver weight and alanine transaminase (ALT) levels, depressed total hepatic glutathione (GSH), increased protein carbonyls and 4-hydroxynonenal (4-HNE) adducted proteins. Treatment with SAMe 1h after APAP overdose (SAMe+APAP) was hepatoprotective and was comparable to NAC+APAP. Treatment with SAMe or NAC 1h after APAP was sufficient to return total hepatic glutathione (GSH) to levels comparable to the VEH group. Western blot showed reversal of APAP mediated effects in the SAMe+APAP and NAC+APAP groups. In summary, SAMe was protective when given 1h after APAP and was comparable to NAC.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Terneus MV,Brown JM,Carpenter AB,Valentovic MAdoi
10.1016/j.tox.2007.10.027subject
Has Abstractpub_date
2008-02-03 00:00:00pages
25-34issue
1eissn
0300-483Xissn
1879-3185pii
S0300-483X(07)00740-8journal_volume
244pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::Exposure of cultured rat mesangial cells to CdCl2 caused a dose- and time-dependent increase in intracellular glutathione that was significant at 0.5 microM and maximal at 1 microM Cd2+. The effect depended on glutathione synthesis and was masked by inhibiting synthesis with buthionine sulfoximine. The cells responded...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(93)90145-i
更新日期:1993-01-29 00:00:00
abstract::Inorganic arsenic (iAs) and its metabolites are transferred to the foetus through the placental barrier and this exposure can compromise the normal development of the unborn. For this reason, we assessed the toxicity of sodium arsenite (iAs(III)) and its metabolites dimethylarsinic acid (DMA(V)), monomethylarsonic aci...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.04.008
更新日期:2008-07-30 00:00:00
abstract::Exposure of pregnant C3H/HeNCR mice to 42.5- or 85-ppm of arsenic as sodium arsenite in drinking water between days 8 and 18 of gestation markedly increases tumor incidence in their offspring. In the work reported here, distribution of inorganic arsenic and its metabolites, methyl arsenic and dimethyl arsenic, were de...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2006.04.041
更新日期:2006-07-05 00:00:00
abstract:PURPOSE:The environmental endocrine disruptors, bisphenol A (BPA) and bisphenol S (BPS) are associated with the development of type 2 diabetes. We aim to study the effects of BPA or BPS exposure on adipokine expression in human adipose tissue and on adipocyte glucose uptake. METHODS:Human subcutaneous adipose tissue w...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2020.152600
更新日期:2020-12-01 00:00:00
abstract::Double-stranded RNA-dependent protein kinase (PKR) is a component of signal transduction pathways mediating various stress signals including oxidative stress and endoplasmic reticulum (ER) stress and is suggested to be implicated in several neurodegenerative diseases. Cell death in neurodegenerative conditions has bee...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2019.02.012
更新日期:2019-04-15 00:00:00
abstract::Trans-1,2-dichloroethylene (t-DCE), an industrial solvent, proved to be moderately toxic when studied in small laboratory animals. In adult female rats brief (8 h) and prolonged (8 h daily, on 5 consecutive days a week, for more than 16 weeks) inhalation of 200 ppm--the current TLV/MAC in various countries--produced h...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(77)90059-2
更新日期:1977-04-01 00:00:00
abstract::A single oral administration of O, O, S-trimethyl phosphorothioate (OOS-Me), an impurity in widely used organophosphorus insecticides, causes delayed toxicity (delayed death) which is accompanied by morphological changes in the bronchiolar epithelium of rat lungs. A series of simple O,O-dimethyl and O,O-diethyl S-alky...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90032-5
更新日期:1984-07-01 00:00:00
abstract::There is concern about the growing environmental levels of brominated dioxins. Brominated dioxins are known to bind and activate the transcription factor aryl hydrocarbon receptor (AhR), as their chlorinated congeners do. However, data on the potency of brominated dioxins for immunotoxicity in vivo is largely lacking,...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.10.024
更新日期:2009-02-04 00:00:00
abstract::The popliteal lymph node assay (PLNA) is being considered as a tool to predict the potential of drugs for inducing systemic autoimmune and hypersensitivity reactions. Despite the use of different technical approaches and the evaluation of over 130 compounds, the sensitivity and specificity of the PLNA are still debata...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.03.010
更新日期:2004-08-05 00:00:00
abstract::Cyclophosphamide (CP) is a known immunomodulating agent. When presented to either late stage chick embryos (e.g. 18 days of incubation (DI] or neonatal chicks. CP induces selective B cell damage resulting in humoral immunosuppression in chickens. The present study was undertaken in order to provide further insights in...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(91)90196-8
更新日期:1991-03-11 00:00:00
abstract::The contributions of the hepatic microsomal and cytosolic fractions in the metabolic activation of the promutagen 2-aminofluorene into mutagenic intermediates in the Ames test were investigated. Rat hepatic postmitochondrial, microsomal and cytosolic preparations could convert 2-aminofluorene to mutagens, the postmito...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(92)90050-o
更新日期:1992-01-01 00:00:00
abstract::Deltamethrin, a synthetic dibromo-pyrethroid insecticide, is extensively used in agriculture, forestry and in household products because of its high activity against a broad spectrum of insect pests (both adults and larvae), its low animal toxicity and its lack of persistence in the environment. Data on the genotoxici...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(98)00097-3
更新日期:1998-09-15 00:00:00
abstract::Oxybutynin hydrochloride, an anti-cholinergic/anti-spasmodic agent, was examined for its effect on fertility and peri-post natal development in the rat and its embryotoxic potential in the rat and rabbit. In the rat effects on reproductive performance included a slight increase in the incidence of foetal malformations...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(86)90044-2
更新日期:1986-07-01 00:00:00
abstract::Testicular injury is often observed in drug development. Serum hormones are usually used as noninvasive biomarkers for testicular injury; however, their sensitivities are low. Therefore, it is difficult to monitor testicular injury in drug development. In recent years, molecules in body fluid exosomes have attracted a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2020.152490
更新日期:2020-07-01 00:00:00
abstract::The osteolathyrogenic agent semicarbazide was assayed for its toxicity and teratogenicity using early embryos of the frog Xenopus laevis. The 96-h LC50 is 1504.20 mg/l while the 96-h EC50 is 76.28 mg/l. Embryo length is altered prior to the onset of other effects indicated by a reduction in stage of development. The m...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(85)90053-8
更新日期:1985-08-01 00:00:00
abstract::Role of chromium(III) in biological systems is controversial and no significant conclusions can be arrived with the available data. Chromium(VI) enters in to the cell readily and gets reduced to form stable chromium(III) complexes. Chromium(III) complexes react slowly and were considered non-toxic. Recent studies sugg...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.07.052
更新日期:2008-09-29 00:00:00
abstract::The effects of cadmium on some mitochondrial enzymes of kidney, testis and lung were investigated in male rats. Rats were injected intraperitoneally with 3 mg Cd/kg body weight and its effects were studied 24, 72 and 144 h later. Succinic dehydrogenase and cytochrome c oxidase activities were significantly inhibited i...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(83)90077-x
更新日期:1983-05-01 00:00:00
abstract::Envenoming by the pitviper Bothrops jararacussu produces cardiovascular alterations, including coagulopathy, systemic hemorrhage, hypotension, circulatory shock and renal failure. In this work, we examined the activity of this venom in rat isolated right atria. Incubation with venom (0.025, 0.05, 0.1 and 0.2mg/ml) cau...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2014.06.010
更新日期:2014-09-02 00:00:00
abstract::One of the most sensitive and reproducible immunotoxic endpoints of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure is suppression of the antibody response to sheep red blood cells (SRBCs) in mice. Immunosuppression occurs in concert with hepatomegaly and associated induction of several hepatic cytochrome P450 enz...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2003.11.016
更新日期:2004-04-01 00:00:00
abstract::Preclinical drug safety assessment includes in vitro studies with physiologically relevant cell cultures. As an in vitro system for hepatic toxicology testing, we have been generating cell clones of human hepatoblastoma cell line HepG2 by lentiviral transduction of phase I cytochrome P450 (CYP) enzymes. Here, we prese...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.11.008
更新日期:2019-01-15 00:00:00
abstract::When Xenopus laevis embryos were treated with fenitrothion, a substantial proportion failed to survive to hatching only when the concentration approached saturation. However, after exposure to 10 ppm of fenitrothion, most were abnormal and did not survive past feeding stage. Different embryonic stages were not equally...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(81)90026-3
更新日期:1981-01-01 00:00:00
abstract::The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, ind...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2007.11.021
更新日期:2008-03-20 00:00:00
abstract::Short term exposure of cultured chick ganglia nerve fibers and neuroglia to selenite produced half maximal inhibitory growth effects in concentrations of 6.2 (2.9--13.0) X 10(-5) M and 1.1 (0.7--1.7) X 10(-4) M, respectively. Complete inhibition of growth for both cell types was apparent at 1 X 10(-3) M, while slight ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(78)90041-0
更新日期:1978-02-01 00:00:00
abstract::Dimethyl sulfoxide (DMSO) has previously been shown to protect against acetaminophen (APAP)-induced hepatotoxicity, but the mechanism of this effect was not clear. Treatment of mice with 1 mg/kg DMSO 4 h before 250 mg/kg APAP resulted in significantly less hepatotoxicity than with APAP alone, as measured by serum glut...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(88)90202-8
更新日期:1988-11-14 00:00:00
abstract::Groundwater arsenic contamination has become a serious global concern due to its adverse effects on human health. Arsenic-induced reactive oxygen species trigger oxidative stress inside mitochondria, which initiate a cascade of events including altered mitochondrial (mt) membrane potential, uncoupling of electron tran...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.06.012
更新日期:2018-09-01 00:00:00
abstract::Heavy metal environmental pollutants increase susceptibility of affected individuals to bacterial and viral infections, but the mechanisms responsible for this effect are not known. We established cellular in vitro systems to identify molecular targets for the action of heavy metal ions. We used two model systems to d...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00483-8
更新日期:2001-12-01 00:00:00
abstract::The action of various manganese organic compounds, which are structural analogs of methylcyclopentadienyl manganese tricarbonyl (MMT), was investigated. Only the cyclopentadienyl manganese tricarbonyl compounds are effective inhibitors of mitochondrial respiration, but only when associated with NAD+-linked substrates....
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(77)90001-4
更新日期:1977-10-01 00:00:00
abstract::The measurement of levels of organic pollutants and/or their metabolites in body tissues or fluids are specific markers of internal dose and, provided that the pharmacokinetic properties of the compounds in question are known, these levels may also be used as predictors of effects. Although historical data still remai...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(95)03017-a
更新日期:1995-07-26 00:00:00
abstract::Prenatal dexamethasone exposure (PDE) could induce testicular developmental toxicity in adults. The present study aims to confirm its intrauterine origination, and to explore its potential intrauterine programming mechanism. The pregnant rats were respectively injected subcutaneously with 0.2 and 0.8 mg/kg d dexametha...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2018.06.005
更新日期:2018-09-01 00:00:00
abstract::The function of the neuromuscular transmission in rats dosed with phoxim (P), methomyl (M), fenvalerate (F), and mixtures of P+M and P+F was studied by using both the stimulation single fiber electromyography (SSFEMG) and repetitive nerve stimulations (RNS) to determine the single muscle fiber action potential and com...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00339-0
更新日期:2001-03-21 00:00:00