Abstract：
:A PB-PK model has been developed for nasal nonreactive vapor uptake in the F344 rat which incorporates nasal enzyme distribution as well as nasal airflow patterns. Nasal tissue is separated into respiratory and olfactory mucosal areas with each area containing mucus, epithelial, and submucosal compartments. Metabolic activities are distributed among the compartments in accordance with published histochemical data, and intercompartmental transfer rate constants are based on molecular diffusivity. Two airflow paths are assumed: a lateral/ventral path which passes over only respiratory mucosa and a dorsal medial path which passes over both respiratory and olfactory mucosa. This model was fit to F344 rat nasal uptake data obtained for five vapors: acetone (an unmetabolized vapor), isoamyl alcohol (alcohol dehydrogenase substrate), ethyl acetate (carboxylesterase substrate), and o-xylene and bromobenzene (mixed function oxidase substrates). These vapors cover a wide span of uptake values ranging from a fractional uptake of less than 0.01 for xylene to 0.80 for isoamyl alcohol. The model accurately predicted the fractional uptake of these vapors, the maximal deviation between actual and predicted values being 0.04. The best fit for the data was obtained assuming: (1) an asymmetric blood flow pattern (with the majority of the blood flow being apportioned to the respiratory mucosa), and (2) only a small fraction of the total airflow (8%) following the dorsal medial pathway and penetrating to the olfactory mucosa. Since only a small fraction of the inspired air passes over the olfactory mucosa, a site with high metabolic activity, an inspiratory flow rate dependence on inspired vapor metabolism results. At low flows, olfactory metabolism is limited by low vapor delivery to that site, an effect that does not occur at high flows. This highlights the potential importance of regional nasal airflow and enzymatic activity patterns in influencing uptake and metabolism of inspired vapors and indicates the need for physiologically relevant models incorporating these factors.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Morris JB,Hassett DN,Blanchard KTdoi
10.1006/taap.1993.1228subject
Has Abstractpub_date
1993-11-01 00:00:00pages
120-9issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(83)71228-7journal_volume
123pub_type
杂志文章abstract：:Low dietary concentrations of methionine and cysteine are known to decrease hepatic glutathione content. However, it is not known if restricting the dietary content of these sulfur containing amino acids also affects hepatic levels of adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the cofactor for sulfation, or meta...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90025-p
更新日期：1990-02-01 00:00:00
abstract：:Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, whi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.07.001
更新日期：2007-11-15 00:00:00
abstract：:Inhalation of methyl chloride (CH3Cl) by male B6C3F1 mice resulted in a concentration-dependent depletion of glutathione (GSH) in liver, kidney, and brain. Exposure for 6 hr to 100 ppm CH3Cl decreased the concentration of GSH in mouse liver by 45%, while exposure to 2500 ppm for 6 hr lowered liver GSH to approximately...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90115-7
更新日期：1984-03-15 00:00:00
abstract：:A pressing need exists to develop and validate molecular biomarkers to assess the early effects of chemical agents, both individually and in mixtures. This is particularly true for new and chemically intensive industries such as the semiconductor industry. Previous studies from this laboratory and others have demonstr...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.01.020
更新日期：2005-08-07 00:00:00
abstract：:Organophosphorus (OP) compounds inhibit mitochondrial enzymes, respiration, and ATP generation, in addition to inducing structural changes such as matrix swelling. This implicates mitochondria as primary subcellular targets for these compounds. In this study, the health and function of cellular mitochondria following ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1999.8741
更新日期：1999-10-01 00:00:00
abstract：:Targeting excessive production of reactive oxygen species (ROS) could be an effective therapeutic strategy to prevent oxidative stress-associated gastrointestinal inflammation. NADPH oxidase (NOX) and mitochondrial complexes (I and II) are the major sources of ROS production contributing to TNF-α/cycloheximide (CHX)-i...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2015.07.007
更新日期：2015-10-15 00:00:00
abstract：:Previous studies performed in this laboratory have shown that certain benzo(a)pyrene (BaP) metabolites, such as benzo(a)pyrene-7,8-dihydrodiol (BaP-7,8-diol) and benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), were more effective in elevating intracellular Ca2+ in normal human peripheral blood mononuclear cell (HP...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1997.8345
更新日期：1998-03-01 00:00:00
abstract：:Exposure of rodents to benzo[a]pyrene (BaP) associated with particles has previously been shown to result in increased retention of BaP and metabolites in lungs. To determine if DNA damage might be enhanced, DNA adducts were measured in lungs of F344 rats following inhalation of pure BaP aerosols or BaP absorbed on ca...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90334-7
更新日期：1989-02-01 00:00:00
abstract：:During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec®). Imatinib targets PDGF, ABL-re...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.04.019
更新日期：2011-08-01 00:00:00
abstract：:Growing concern suggests that some chemicals exert (developmental) neurotoxicity (DNT and NT) and are linked to the increase in incidence of autism, attention deficit and hyperactivity disorders. The high cost of routine tests for DNT and NT assessment make it difficult to test the high numbers of existing chemicals. ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.02.003
更新日期：2018-09-01 00:00:00
abstract：:Metallothionein (MT), a high-affinity metal-binding protein, is known to detoxicate cadmium and may play an important role in cadmium carcinogenesis. In the rat, the ventral lobe of the prostate is sensitive to cadmium carcinogenesis, while the dorsolateral lobe is refractory. The possibility exists that the basis of ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1995.1097
更新日期：1995-05-01 00:00:00
abstract：:Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish. Tre...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.11.016
更新日期：2008-05-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0094
更新日期：1996-05-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1998.8460
更新日期：1998-09-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90081-x
更新日期：1985-09-15 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：:To elucidate the underlying mechanisms in oxidative stress-related airway remodeling observed in chronic inflammatory pulmonary diseases such as asthma, we studied the effects of a thiol antioxidant, N-acetylcysteine (NAC), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AG-1478, and tyr...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2002.9514
更新日期：2002-11-01 00:00:00
abstract：:Previous work from our group indicated that alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) potentially play a role in methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) neurotoxicity. The aims of the present study were two-fold: (1) to demonstrate the interaction of METH and MDMA with homomer...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.05.015
更新日期：2007-09-15 00:00:00
abstract：:Acetaminophen (APAP) nephrotoxicity has been observed both in humans and research animals. Recent studies suggest a contributory role for glutathione (GSH)-derived conjugates of APAP in the development of nephrotoxicity. Inhibitors of either gamma-glutamyl transpeptidase (gamma-GT) or the probenecid-sensitive organic ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2004.06.030
更新日期：2005-01-15 00:00:00
abstract：:Simple alkylating agents induce cell death by activating the apoptotic pathway. In rodent fibroblasts, apoptosis triggered by DNA methylation lesions is executed via the mitochondrial damage pathway. Here, we studied cell death induced by the methylating agents methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nit...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2005.02.034
更新日期：2005-09-01 00:00:00
abstract：:Chronic inhalation of high concentrations of respirable quartz particles has been implicated in various lung diseases including lung fibrosis and cancer. Generation of reactive oxygen species (ROS) and oxidative stress is considered a major mechanism of quartz toxicity. Curcumin, a yellow pigment from Curcuma longa, h...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.10.002
更新日期：2008-02-15 00:00:00
abstract：:Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.07.022
更新日期：2011-11-01 00:00:00
abstract：:Mitotic catastrophe, a form of cell death resulting from abnormal mitosis, is a cytotoxic death pathway as well as an appealing mechanistic strategy for the development of anti-cancer drugs. In this study, 6-bromine-5-hydroxy-4-methoxybenzaldehyde was demonstrated to induce DNA double-strand break, multipolar spindles...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.03.003
更新日期：2011-05-01 00:00:00
abstract：:We use a stochastic model describing initiation and clonal growth of altered cells to analyze data from an initiation-promotion hepatocarcinogenesis experiment in female Wistar rats. Starting at 7 weeks of age, the animals were treated for 10 days with the initiating agent diethylnitrosamine (DEN, 10 mg/kg body wt per...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.8980
更新日期：2000-08-15 00:00:00
abstract：:High fetal and neonatal brain levels of methyl mercury (MeHg) have been associated with the abnormal migration of neurons within the cerebellar and cerebral cortices. How MeHg interferes with cellular proliferation, migration, and differentiation is poorly understood. In this study, a cell recognition/cohesion assay b...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90363-7
更新日期：1986-12-01 00:00:00
abstract：:Inhalation of ozone (O3) has been associated with development of inflammation in the respiratory airways and a variety of alterations in pulmonary function. Epithelial cells lining the airways are the first cells with which inhaled O3 comes into contact and thus represent a potential major target of acute O3 toxicity....
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1994.1135
更新日期：1994-07-01 00:00:00
abstract：:Hepa 1c1c7 (WT), TAOc1BPrc1 (CI), and BPrc1 (CII) mouse hepatoma cells were exposed to benzo[e]pyrene (B[e]P) or benzo[a]pyrene (B[a]P). B[e]P induced activity of a rat CYP1A1 reporter gene construct (-3015 to +2545 bp) by 1.8- to 2-fold and 5-fold in WT and CI cells, respectively. B[e]P caused a 2-fold induction of a...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1994.1175
更新日期：1994-09-01 00:00:00
abstract：BACKGROUND:Perchloroethylene (perc) induced target organ toxicity has been associated with tissue-specific metabolic pathways. Previous physiologically-based pharmacokinetic (PBPK) modeling of perc accurately predicted oxidative metabolites but suggested the need to better characterize glutathione (GSH) conjugation as ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.05.033
更新日期：2018-08-01 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：:Tabun represents the phosphoramidate class of organophosphates that are covalent inhibitors of acetylcholinesterase (AChE), an essential enzyme in neurotransmission. Currently used therapy in counteracting excessive cholinergic stimulation consists of a muscarinic antagonist (atropine) and an oxime reactivator of inhi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2019.04.007
更新日期：2019-06-01 00:00:00
