Abstract:
:The effect of HgCl2 on kainate (KA)-induced depression of voltage-gated potassium (K+) current in chick embryo telencephalic cells was studied using conventional and nystatin-perforated whole-cell patch-clamp recordings, fluorescence imaging, and flow cytometry techniques. Hg2+ (1 microM) alone did not effect the 4-aminopyridine-(4-AP)-sensitive transient K+ current in immature cells (Embryonic Day 5), but irreversibly potentiated the depressant effect of KA on this K+ current. A 50% potentiation of KA-induced depression of the K+ current was produced by an application of 0.19 microM Hg2+. Application of ionomycin (5 microM) or calcium ionophore A23187 (2 microM) suppressed the K+ current. To test the possibility that the 4-AP-sensitive transient K+ current is a Ca-inactivated current, the effect of intracellular Ca2+ concentration ([Ca2+]i) in the range of 30 nM to 2 microM was determined. The amplitude of the K+ current was sensitive to [Ca2+]i with half-maximal inactivation at 370 nm at +60 mV. The concentration-response curve of the K+ current inhibition by [Ca2+]i was shifted to lower [Ca2+]i and the slope of the curve was reduced in the presence of KA. Hg2+ potentiated these effects of KA. The Ca-dependence of the K+ current was maximal at the 5th embryonic day, declined to the 9th embryonic day, and was absent at the 11th embryonic day. Application of Hg2+ (0.1-1 microM) had no effect on the basal [Ca2+]i of freshly dissociated cells (10th day in ovo) and cells in culture (the 4-day cultures from the telencephalon of 5-day-old embryos), but potentiated KA-induced increase of [Ca2+]i in a Ca-free-EGTA solution in a concentration-dependent manner. Moreover 1 microM Hg2+ delayed and reduced the recovery to basal [Ca2+]i after washout of KA. Exposure to 5-30 microM H2+ caused an irreversible decline of membrane resistance, an increased cell size, and reduced cell granularity and complexity. Intracellular recording of spontaneous neuronal activity and immunocytochemical identification showed that the KA/Hg2+-sensitive Ca-inactivated K+ current exists in early differentiating telencephalic neurons. Because depression of the K+ current by KA and Hg2+ decreases the interspike interval and irreversibly perturbs the frequency code of information in the nervous system, the expression of this current during early neuroembryogenesis may be one of the reasons for the developmental toxicity of inorganic mercury.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Dyatlov VA,Platoshin AV,Lawrence DA,Carpenter DOdoi
10.1006/taap.1996.0127subject
Has Abstractpub_date
1996-06-01 00:00:00pages
285-97issue
2eissn
0041-008Xissn
1096-0333pii
S0041-008X(96)90127-1journal_volume
138pub_type
杂志文章abstract::The distribution and exact cellular localization of mercury in the brain and upper cervical spinal cord of the adult male Wistar rat has been determined using the autometallographic silver-enhancement technique. A detailed atlas of mercury-containing nuclei following oral administration of HgCl2 (20 mg x liter-1 or CH...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90092-s
更新日期:1991-05-01 00:00:00
abstract::In order to assess the effects of long-term exposure to cadmium (Cd) on the renal metabolism of eicosanoids, the urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2) was determined in 37 workers exposed to Cd and...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(92)90294-3
更新日期:1992-10-01 00:00:00
abstract::The use of toxicokinetic (TK) data is becoming more prevalent in the evaluation of food ingredient safety as more TK information is being incorporated in safety data packages. Data demonstrating "1) the extent of absorption, 2) tissue distribution, 3) pathways and rates of metabolism, and 4) rate(s) of elimination" of...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2019.114759
更新日期:2019-11-01 00:00:00
abstract::Health agencies are often required to predict the effects of long term low level exposure in humans based on annual data involving short-term high-level exposures. Uncertainties in extrapolation can be, in part, based on potentially different mechanism associated with different exposure scenarios. This study evaluated...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0155
更新日期:1996-07-01 00:00:00
abstract::Diesel exhaust particles (DEPs) cause many adverse health problems, and reports indicate increased risk of breast cancer in men and women through exposure to gasoline and vehicle exhaust. However, DEPs include vast numbers of compounds, and the specific compound(s) responsible for these actions are not clear. We recen...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.02.027
更新日期:2008-08-01 00:00:00
abstract::In rat hepatocytes and isolated liver mitochondrial fractions, Cyclosporine A (CsA) is often used as a specific inhibitor of mitochondrial Ca(2+) release and as a specific blocker of mitochondrial membrane potential and permeability transition (MPT), which are all processes involved in the inhibition of apoptosis. How...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8887
更新日期:2000-03-15 00:00:00
abstract::Previous studies have demonstrated that mice lacking a functional folate binding protein 2 gene (Folbp2-/-) were significantly more sensitive to in utero arsenic exposure than were the wild-type mice similarly exposed. When these mice were fed a folate-deficient diet, the embryotoxic effect of arsenate was further exa...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2004.07.006
更新日期:2005-02-15 00:00:00
abstract::Treatment with 3-aminobenzamide, known as an inhibitor of poly(ADP-ribose)polymerease, decreased the toxicity and covalent binding of the herbicide dichlobenil (2,6-dichlorobenzonitrile; 12 mg/kg; i.p.) in the mouse olfactory mucosa. In vitro studies showed that 3-aminobenzamide markedly reduced the NADPH-dependent co...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0039
更新日期:1996-02-01 00:00:00
abstract::The radioprotective effect of extracellular melanin, a naturally occurring pigment, isolated from the fungus Gliocephalotrichum simplex was examined in BALB/C mice, and the probable mechanism of action was established. At an effective dose of 50mg/kg body weight, melanin exhibited both prophylactic and mitigative acti...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.08.002
更新日期:2012-10-15 00:00:00
abstract::Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidativ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.05.006
更新日期:2008-09-15 00:00:00
abstract:INTRODUCTION:Noncirrhotic portal fibrosis has been reported to occur in humans due to prolonged intake of arsenic contaminated water. Further, oxystress and hepatic fibrosis have been demonstrated by us in chronic arsenic induced hepatic damage in murine model. Cytokines like tumor necrosis factor alpha (TNF-alpha) and...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2004.08.010
更新日期:2005-04-01 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::Recently, Gray and Ostby (Toxicol. Appl. Pharmacol. 133, 285-294, 1995) reported that in utero and lactational TCDD exposure causes striking abnormalities in the rat female reproductive system, including reduced fecundity and vaginal threads. The mechanism by which TCDD induces such abnormalities is unknown. Thus, we ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8295
更新日期:1997-12-01 00:00:00
abstract::Combretastatin A-4 (CA-4) has already entered clinical trials of solid tumors over ten years. However, the limited anticancer activity and dose-dependent toxicity restrict its clinical application. Here, we offered convincing evidence that CA-4 induced autophagy in various cancer cells, which was demonstrated by acrid...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.11.018
更新日期:2014-01-15 00:00:00
abstract::Garlic and its active components are known to possess antioxidant and antiinflammatory effects. The present study investigated the effects of garlic oil and its organosulfur compounds on endotoxin-induced intestinal mucosal damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil (GO), 0.5 mmol/kg...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.08.008
更新日期:2006-05-15 00:00:00
abstract::Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. After iv administration of gentamicin, 10 to 30 mg/kg, its plasma levels were elevated in mice given morphine, 20 mg/kg sc. Plasma clearance of gentamicin was nearly halved by morphine, due primarily to lowering of the eli...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90044-0
更新日期:1988-05-01 00:00:00
abstract::Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.11.016
更新日期:2011-02-15 00:00:00
abstract::The restoration of plasma acetylcholinesterase activity in mice following inhibition by organophosphorus pesticides and nerve agents has been attributed to synthesis of new enzyme. It is generally assumed that activity levels return to normal, are stable and do not exceed the normal level. We have observed over the pa...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.06.021
更新日期:2011-09-01 00:00:00
abstract::Beryllium (Be+2), a divalent metal ion, is toxic to both man and animal. Although the molecular basis for its toxicity is unknown, it is well established that micromolar concentrations of beryllium specifically inhibit certain enzymes. Previous in vitro studies have shown that the presence of ferritin, an iron-storage...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90211-5
更新日期:1986-02-01 00:00:00
abstract::The rapid development of high-volume horizontal hydraulic fracturing for mining natural gas from shale has posed potential impacts on human health and biodiversity. The produced flow back waters after hydraulic stimulation are known to carry high levels of saline and total dissolved solids. To understand the toxicity ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.07.011
更新日期:2015-10-01 00:00:00
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::Dietary 2(3)-tert-butyl-4-hydroxyanisole (BHA) treatment has been shown to increase hepatic glutathione (GSH) content in rats and mice. Subsequent studies in our laboratory have demonstrated that hepatic gamma-glutamylcysteine synthetase (GCS) activity is increased in mice treated with dietary BHA. To test whether thi...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1101
更新日期:1994-05-01 00:00:00
abstract::Pretreatment of rats with the polychlorinated biphenyl (PCB) Aroclor 1254 or phenobarbital markedly increased the duodenal ulcerogenic action of acrylonitrile. The extent of forestomach and hepatic lesions in these rats, on the other hand, was not modified. The duodenal ulcers produced by Aroclor 1254 and acrylonitril...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90034-0
更新日期:1983-12-01 00:00:00
abstract::We previously demonstrated that cisplatin administration in mice induces muscle atrophy and an increase in the expression of two muscle-specific ubiquitin E3 ligase genes, muscle ring finger protein 1 (MuRF1), and atrophy gene-1 (atrogin-1), in skeletal muscle. Ubiquitination serves as a degradation signal in both the...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.115165
更新日期:2020-09-15 00:00:00
abstract::Endothelial-mesenchymal transition (EndMT) is a frequent event in endothelial dysfunction, which is associated with pulmonary arterial hypertension (PAH). MiR-181 family members exert diverse effects in multiple biological processes. However, the relationships between miR-181b-5p (miR-181b) and EndMT in PAH are not we...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114827
更新日期:2020-01-01 00:00:00
abstract::Colchicine-specific antibody (IgG(C] was tested in mice for reversal of colchicine toxicity. The mouse model was chosen because it reflects human pathophysiology in colchicine poisoning. IgG(C) was administered when at least 85% of colchicine was distributed in tissues. It resulted in a dramatic decrease in lethality ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90172-q
更新日期:1990-07-01 00:00:00
abstract::Learning and memory deficits are obvious symptoms that develop over time in patients with poorly controlled diabetes. Hyperactivity of the renin-angiotensin system (RAS) is directly associated with β-cell dysfunction and diabetic complications, including cognitive impairment. Here, we investigated the protective and m...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.114954
更新日期:2020-05-01 00:00:00
abstract::Increased incidence of mortality and morbidity due to cardiopulmonary complications has been found to associate with elevated levels of particulate air pollution (particulate matter with an aerodynamic diameter < 10 microm, PM10 and <2.5 microm, PM2. 5). Lung injury and an imbalance of inflammatory mediators are propo...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8591
更新日期:1999-03-15 00:00:00
abstract::Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct c...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.06.014
更新日期:2013-10-15 00:00:00
abstract::Pulmonary fibrosis is a consequence of severe injury from some toxic agents including high doses of ozone. It is not known, however, whether chronic exposure to low doses of ozone, such as those encountered in polluted ambient atmospheres, could also result in abnormal accumulations of lung collagen. Rats were exposed...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90184-6
更新日期:1988-03-15 00:00:00