Abstract:
:The influence of GSH concentration on metabolism of monocrotaline was examined in the isolated, perfused rat liver. Chloroethanol (0.37 mmol/kg), diethyl maleate (5.6 mmol/kg), and buthionine sulfoximine (72.9 mmol/kg) given in vivo reduced hepatic GSH from 3.7 mumol/g wet weight to 1.5, 0.6 and 0.9 mumol/g, respectively. Livers were then perfused in vitro for 1 hr with monocrotaline (0.5 mM). GSH depletion had no effect on the total release of pyrrolic metabolites of monocrotaline. Depletion, however, markedly affected the pattern of pyrrole release. Biliary release of 7-glutathionyl-6,7-dihydro-1-hydroxy-methyl-5H-pyrrolizine (GSDHP) was reduced by up to 72%. Pretreatment with diethyl maleate or buthionine sulfoximine increased the level of protein-bound pyrroles in the liver by 107 and 84%, respectively. Such pyrroles are probably responsible for liver toxicity. GSH depletion also led to a doubling of dehydromonocrotaline release into the perfusate. This metabolite is probably responsible for the extrahepatic toxicity of monocrotaline. Release into perfusate of the relatively nontoxic metabolite, 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) was correspondingly decreased. Hepatic GSH content was increased to 4.4 mumol/g by pretreatment with oxo-4-thiazolidine carboxylate (4.76 mmol/kg). This agent increased total pyrrolic metabolites by 54%. Biliary release of GSDHP and perfusate release of dehydromonocrotaline and DHP were all increased. Thus, hepatic GSH levels regulate the metabolism of monocrotaline and dehydromonocrotaline and, consequently, the hepatic and extrahepatic toxicity of monocrotaline. GSH depletion leads to a switch from the biliary release of the midly toxic GSDHP to the perfusate release of the highly toxic dehydromonocrotaline. GSH depletion also permits more dehydromonocrotaline in the liver to become available for macromolecular alkylation. These findings suggest that nutritional intake of sulfur-containing amino acids can influence the severity of pyrrolizidine poisoning.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Yan CC,Huxtable RJdoi
10.1006/taap.1995.1017subject
Has Abstractpub_date
1995-01-01 00:00:00pages
132-9issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(85)71017-4journal_volume
130pub_type
杂志文章abstract::The effect of Type 1 diabetes on the toxicity of thioacetamide was investigated in a murine model. In streptozotocin-induced diabetic C57BL6 mice a LD90 dose of thioacetamide (1000 mg/kg, ip in saline) caused only 10% mortality. Alanine aminotransferase activity revealed approximately 2.7-fold less liver injury in the...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(02)00037-6
更新日期:2003-04-15 00:00:00
abstract::Cannabinoid receptor (CB) expression was characterized in immunological cell and tissue preparations. Northern analysis revealed approximately 6-kb transcripts for CB1 (brain-type) in mouse spleen and brain and in rat cerebellum. CB1 was not detected in mouse thymus or rat spleen RNA by Northern analysis. CB2 (periphe...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.8034
更新日期:1997-02-01 00:00:00
abstract::1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin is a chemical inducer of Parkinson's disease (PD) whereas N-methylated beta-carbolines and isoquinolines are naturally occurring analogues of MPTP involved in PD. This research has studied the oxidation of MPTP by human CYP2D6 (CYP2D6*1 and CYP2D6*10 allel...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.06.003
更新日期:2006-11-01 00:00:00
abstract::Cadmium chloride (CdCl2) at a dose of 1 mg/kg of body weight was injected into male Wistar rats twice a day (12-hr intervals) for 7 consecutive days. A group of treated rats was maintained without any treatment for an additional period of 10 days and killed on the following day (on Day 18). Plasma aldosterone concentr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90346-6
更新日期:1984-12-01 00:00:00
abstract::Following po administration of a nephrotoxic dose (200 mg/kg) of hexachloro-1:3-butadiene (HCBD) to male rats, the principal route of excretion was biliary, 17-20% of the dose being eliminated on each of the first 2 days. Fecal excretion over this period was less than 5% of the dose per day, suggesting enterohepatic r...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90061-9
更新日期:1984-03-30 00:00:00
abstract::Metabolism of methylene chloride, or dichloromethane (DCM), plays a key role in determining the kinetics and carcinogenicity of the halocarbon. The objectives of this study were: to evaluate and optimize the vial equilibration technique, originally described by Sato and Nakajima (1979a), in order to characterize the h...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0163
更新日期:1996-08-01 00:00:00
abstract::Acute exposure to Cd produces liver injury, whereas chronic exposure results in kidney injury. Tolerance to the hepatotoxicity is observed during chronic exposure to Cd due to the induction of metallothionein (MT). The nephrotoxicity produced by chronic Cd exposure purportedly results from renal uptake of Cd-metalloth...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90231-1
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abstract::The farnesoid X receptor (FXR) is a bile acid-activated transcription factor belonging to the nuclear receptor superfamily. FXR deficiency in mice results in cholestasis, metabolic disorders, and tumorigenesis in liver and intestine. FXR is known to contribute to pathogenesis by regulating gene transcription; however,...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.11.012
更新日期:2013-01-15 00:00:00
abstract::Neonatal and adult rats (1, 2, 3, 6, and 12 weeks of age) were given five daily oral doses of di(2-ethylhexyl) phthalate (DEHP) (0, 10, 100, 1000, 2000 mg/kg) and histological changes in the testes were examined 24 hr after the last dose. Relative testis weights were reduced at doses of 1000 mg/kg in 1, 2, 3, and 6-we...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(88)80012-7
更新日期:1988-08-01 00:00:00
abstract::Nonmelanoma skin cancer is the most common cancer among humans and solar UV radiation, particularly its UVB component (290-320 nm), is its major cause. One way to reduce the occurrence of the cancer is via the use of substances (often antioxidants) termed "photochemopreventive agents". Resveratrol (trans-3,4',5-trihyd...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(02)00014-5
更新日期:2003-01-01 00:00:00
abstract::Previous work has shown that chlordecone (CD)-amplified CCl4 hepatotoxicity and lethality can be mitigated by pretreatment with cyanidanol. These studies also revealed that stimulated hepatocellular regeneration might play an important role in the cyanidanol protection of CD-amplified CCl4 toxicity. The present studie...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90268-j
更新日期:1991-03-15 00:00:00
abstract::In many neuropathologies activated microglia and macrophages cause neurotoxicity and prolong the inflammatory response. We have previously characterized the glycosphingolipid Neurostatin (Nst), which potentially reduces these detrimental mechanisms. Nst, isolated from mammalian brain, is the GD1b ganglioside with O-ac...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114627
更新日期:2019-08-15 00:00:00
abstract::The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1'-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, v...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.12.009
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abstract::Interference of exogenous chemicals with the aromatase enzyme can be useful as a tool to identify chemicals that could act either chemopreventive for hormone-dependent cancer or adverse endocrine disruptive. Aromatase is the key enzyme in the biosynthesis of steroids, as it converts androgens to estrogens. Certain fla...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.12.007
更新日期:2008-05-01 00:00:00
abstract::To characterize modes of action of substances and their cytotoxic effects Bionas GmbH has developed a new screening system to allow the continuous recording of how an active substance can act (Bionas 2500 analyzing system). In the pharmaceutical industry it is important to acquire as much information as possible about...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.12.027
更新日期:2007-04-01 00:00:00
abstract::Doxorubicin (DOX) is a potent anti-neoplastic antibiotic used to treat a variety of malignancies; however, its use is limited by dose-dependent cardiotoxicity. Moreover, there is a strong correlation between cytochrome P450 (CYP)-mediated arachidonic acid metabolites and the pathogenesis of many cardiovascular disease...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.09.012
更新日期:2010-01-01 00:00:00
abstract::Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without co...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.11.020
更新日期:2012-02-01 00:00:00
abstract::Epidemiological studies have demonstrated a high association of inorganic arsenic exposure with vascular diseases. Recent research has also linked this vascular damage to impairment of endothelial nitric oxide synthase (eNOS) function by arsenic exposure. However, the role of eNOS in regulating the arsenite-induced va...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.03.001
更新日期:2005-11-01 00:00:00
abstract::The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposom...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.09.011
更新日期:2012-11-15 00:00:00
abstract::2,3- and 3,4-Dichlorophenyl methyl sulfoxides and 2,3- and 3,4-dichlorophenyl methyl sulfones (2,3- and 3,4-DCPSO2Mes) were detected in the urine of rats administered o-dichlorobenzene (o-DCB). After administration of o-DCB to rats, swift decreases were observed in the concentrations of o-DCB in blood, liver, and kidn...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8191
更新日期:1997-08-01 00:00:00
abstract::Inhaling concomitants from Asian sand dust (ASD) may result in exacerbation of pneumonia by the pathogen. The exacerbating effect of ASD on pneumonia induced by Klebsiella pneumoniae (KP) was investigated in ICR mice. The organic substances adsorbed onto ASD collected from the atmosphere of Iki-island in Japan were ex...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.11.003
更新日期:2012-01-15 00:00:00
abstract::Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxida...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.05.012
更新日期:2009-08-15 00:00:00
abstract::This study was undertaken to determine the ability of a series of 19 compounds representing different chemical classes of carcinogens to induce lung tumors in strain A/J mice after either ip or po administration. Aflatoxin B1, dibutylnitrosamine, 1,2-dimethylhydrazine, and methylnitrosourea induced a significant incre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90433-3
更新日期:1986-01-01 00:00:00
abstract::Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with ve...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.11.005
更新日期:2007-03-01 00:00:00
abstract::Recent advances have been made in our understanding of the roles played by cutaneous dendritic cells (DCs) in the induction of contact allergy. A number of associated changes in epidermal Langerhans cell phenotype and function required for effective skin sensitization are providing the foundations for the development ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2007.03.006
更新日期:2007-06-15 00:00:00
abstract::The relative methemoglobin (MetHgb) forming ability of two metabolites of dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine (MADDS-NOH), were compared in rat and human whole blood. Concentration-response curves for the two metabolites were generated in vitro in whole blood. Data were fit to ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1255
更新日期:1994-12-01 00:00:00
abstract::Amphetamine has been shown previously to increase levels of the inducible 70-kDa heat shock protein (hsp70i) in mouse liver. In the present study, the hepatic concentrations of a variety of hsps in livers of mice pretreated with amphetamine (15 mg/kg, i.p.) were evaluated, and the time course of hsp induction was exam...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8290
更新日期:1997-12-01 00:00:00
abstract::Vinyl carbamate epoxide (VCO) is believed to be the metabolite of ethyl carbamate (EC) ultimately responsible for its carcinogenic effects. This study investigates the role of glutathione (GSH) in protection against VCO-mediated adduct formation, and the involvement of glutathione S-transferases (GSTs) in detoxificati...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1213
更新日期:1995-11-01 00:00:00
abstract::Lead (Pb) exposure at high concentrations is associated with poor sperm quality, acrosome alterations, and low fertilization rate. Sperm capacitation and the acrosome reaction (AR) are required for successful fertilization. Actin polymerization is crucial for correct capacitation, and small GTPases, such as RhoA, Rac1...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114694
更新日期:2019-10-01 00:00:00
abstract::Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Capsaicin, which is th...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.11.029
更新日期:2013-02-01 00:00:00