3-nitropropionic acid-induced neurotoxicity: Topics by WorldWideScience.org

Neurotoxic and pharmacokinetic responses to trichloroethylene as a function of exposure scenario.

For some neurotoxic chemicals, neurobehavioral effects are now considered to be among the most sensitive end points yet detected, particularly if exposures occur during critical windows of vulnerability....Full Text Available

1999-06-01

Enzymatic and pharmacological activities of Micrurus (coral) snake venoms. I-neurotoxicity and inhibition of 3H-L-glutamate uptake induced by M. lemniscatus carvalhoi venom

Strategies are needed for assessing the risks of exposures to airborne toxicants that vary over concentrations and durations. The goal of this project was to describe the relationship between the concentration...Full Text Available

2000-05-01

Protracted neurotoxicity from chlordane sprayed to kill termites.

No abstract prepared.

2004-07-01

Neurobehavioral Deficits and Increased Blood Pressure in School-Age Children Prenatally Exposed to Pesticides

Over 250 adults and children were exposed to chlordane when the wooden building surfaces and soil around an apartment complex were sprayed in 1987. Two hundred-sixteen adults had neurobehavioral functions...Full Text Available

1995-07-01

Monitoring potential neurotoxic effects of hazardous waste disposal

BackgroundThe long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood...Full Text Available

2010-06-01

Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction

This report reviews neurotoxicological principles relevant to situations of hazardous waste disposal. Some of the diagnostic techniques currently used for field assessment of nervous system dysfunction...Full Text Available

1983-02-01

Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

BackgroundMethamphetamine (METH), an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial...Full Text Available

Behavioral Defects in Chaperone-Deficient Alzheimer's Disease Model Mice

Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the...Full Text Available

2010-08-01

Assessing phytoremediation potentials of selected tropical plants for acrylamide

Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Aβ) aggregates and their deposition in senile plaques are...Full Text Available

Amyloid Oligomer Neurotoxicity, Calcium Dysregulation, and Lipid Rafts

In biotechnology, acrylamide is being used in DNA and RNA analysis using the polyacrylamide gel electrophoreses procedure. Polymerized acrylamide is degraded into acrylamide through time; it is converted into a hazardous contaminant that is carcinogenic and neurotoxic to animals and humans. Because ...

Recombinant human activated protein C ameliorates oleic acid-induced lung injury in awake sheep

Amyloid proteins constitute a chemically heterogeneous group of proteins, which share some biophysical and biological characteristics, the principal of which are the high propensity to acquire an incorrect...Full Text Available

Differential recognition of viral RNA by RIG-I

IntroductionAcute lung injury (ALI) may arise both after sepsis and non-septic inflammatory conditions and is often associated with the release of fatty acids, including oleic acid...Full Text Available

2008-01-01

Neurotoxicity and bony diseases caused by the continuous contamination with aluminum of solutions of renal dialysis

Retinoic acid inducible gene I (RIG-I) is a pattern recognition receptor (PRR) responsible for detection of nucleic acids from pathogens in the cytoplasm of infected cells and induction of type I interferon...Full Text Available

2011-03-01

Blood gene expression markers to detect and distinguish target organ toxicity

This article reviews the principal evidences about aluminum neurotoxicity in vitro, and some evidences in brain tissues of Alzheimer patients; and also show some studies realized with human that suffer renal deficiencies, dealing whit the principal osteodystrophy. The problem of analyzing low aluminum concentration in human fluids is overcome with very sensitive analytical methods as electrothermal atomic absorption spectrometry (ETAS) and voltammetric methods as Anodic Striping Voltammetry with complexing agents that easing adsorption over solid electrodes or mercury hanging drops. Is a vital question to know with accuracy the aluminum concentration in water used in hemodialysis or in fluids used in ambulatory peritoneal dialysis, as a first stage to prevent contamination by aluminum. So the prevention of contamination during sapling storage and analysis of biological fluids should be the first need and the sources of water used in renal dialysis keep be as clean ...

2001-01-01

British Library Electronic Table of Contents (United Kingdom)

The purpose of this study was to investigate whether the expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ toxicity induced by chemicals in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or a neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities. Similarly, administration of methyl parathion (MP) resulted in neurotoxicity in the rats as evidenced from the inhibition of acetyl cholinesterase activity in their blood. Administration of either chemical also resulted in mild hematotoxicity in the rats. Microarray analysis of the global ...

2010-01-01

Selective downregulation of retinoic acid-inducible gene I within the intestinal epithelial compartment in crohn's disease

British Library Electronic Table of Contents (United Kingdom)

AbstractBackground: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD). Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25). Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) with...

2011-01-01

A System-Based Comparison of Gene Expression Reveals Alterations in Oxidative Stress, Disruption of Ubiquitin-Proteasome System and Altered Cell Cycle Regulation after Exposure to Cadmium and Methylmercury in Mouse Embryonic Fibroblast

Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice.

Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of...Full Text Available

2010-04-01

Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

Excitotoxicity plays a major role in various neurological disorders. In this study, we explored the behavioral and neurotoxic effects of intraventricular NMDA administration in mice. After NMDA injection, acute seizures were followed by impairments in locomotor activity, motor performance on a rotarod, and climbing ability. Mice killed 1 day after NMDA administration showed increased synaptosomal reactive oxygen species ROS production and calcium concentration and decreased mitochondrial membrane potential, mitochondrial reductase activities, and neuronal membrane Na+, K+ -ATPase and mg2+ -ATPase activities. One and 3 days after excitotoxic injury, Golgi stains showed that dendritic length and spine density were significantly decreased in neurons of the hippocampal dentate gyrus. Some mice received honokiol, tea polyphenol plus memantine, and honokiol plus memantine prior to NMDA treatment; the occurrence of generalized seizures was attenuated, seizure scores were ...

2010-08-01

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Physiologically Based Pharmacokinetic Modeling of Fetal and Neonatal Manganese Exposure in Humans: Describing Manganese Homeostasis during Development

Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe_2O_3 nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 #mu#g) intranasal exposure of nano- and submicron-sized Fe_2O_3 particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe_2O_3 particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe_2O_3 particle treatment (p < 0.05). The ...

2009-01-01

British Library Electronic Table of Contents (United Kingdom)

Concerns for potential vulnerability to manganese (Mn) neurotoxicity during fetal and neonatal development have been raised due to increased needs for Mn for normal growth, different sources of exposure to Mn, and pharmacokinetic differences between the young and adults. A physiologically based pharmacokinetic (PBPK) model for Mn during human gestation and lactation was developed to predict Mn in fetal and neonatal brain using a parallelogram approach based upon extrapolation across life stages in rats and cross-species extrapolation to humans. Based on the rodent modeling, key physiological processes controlling Mn kinetics during gestation and lactation were incorporated, including alterations in Mn uptake, excretion, tissue-specific distributions, and placental and lactational transfer ...

2011-01-01

Manganese-Induced NF-kB Activation and Nitrosative Stress Is Decreased by Estrogen in Juvenile Mice

British Library Electronic Table of Contents (United Kingdom)

Manganese toxicity can cause a neurodegenerative disorder affecting cortical and basal ganglia structures with a neurological presentation resembling features of Parkinson's disease. Children are more sensitive to Mn-induced neurological dysfunction than adults, and recent studies from our laboratory revealed a marked sensitivity of male juvenile mice to neuroinflammatory injury from Mn, relative to females. To determine the role of estrogen (E2) in mediating sex-dependent vulnerability to Mn-induced neurotoxicity, we exposed transgenic mice expressing an NF-kB-driven enhanced green fluorescent protein (EGFP) reporter construct (NF-kB-EGFP mice) to Mn, postulating that supplementing male mice with E2 during juvenile development would attenuate neuroinflammatory changes associated with glia...

2011-01-01

Differential immunotoxic effects of inorganic and organic mercury species in vitro

British Library Electronic Table of Contents (United Kingdom)

Despite the fact that humans are exposed to multiple forms of mercury (elemental, inorganic, and organic), most research on mercury toxicity has focused on methylmercury (MeHg) and on neurotoxic outcomes and mechanisms. Recent work has indicated that the immunotoxic effects of mercury compounds may be significant contributors to human disease as well as mechanistically relevant to other target organ toxicities. In this study, we compared the effects of inorganic Hg (iHg) to organic Hg species (MeHg and ethylmercury, EtHg) in human peripheral blood mononuclear cells (PBMCs) in vitro at sub-cytotoxic concentrations, using methods developed to characterize response of human PBMCs to iHg in vitro. PBMCs were isolated from six volunteer blood donors (three males and three females) and cultured ...

2010-01-01

Comparative effects of ten dithiocarbamate and thiuram compounds on tissue distribution and excretion of lead in rats

A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in a-synuclein transgenic C. elegans

The dithiocarbamate and thiuram compounds, including disulfiram, were compared for their efficacies in influencing tissue distribution of a trace dose of intravenously injected lead plus "2"0"3Pb in rats. The tested compounds were sodium diethyldithiocarbamate (DEDTC), sodium dimethyldithiocarbamate (DMDTC), tetraethylthiuram disulfide (disulfiram), a complex of zinc and manganese ethylenebisdithiocarbamate (mancozeb), manganese ethylenebisdithiocarbamate (maneb), sodium monomethyldithiocarbamate (metham), zinc propylene bisdithiocarbamate (propineb), tetramethylthiuram disulfide (thiram), zinc ethylenebisdithiocarbamate (zineb), and zinc dimethyldithiocarbamate (ziram). The results of this study show that interactions can occur between lead and DEDTC, DMDTC, disulfiram, metham, thiram, and ziram, resulting in increased levels of lead in brain and probably potentiation of the neurotoxic effects of lead.

British Library Electronic Table of Contents (United Kingdom)

Mutations or multiplications in a-synuclein gene cause familial forms of Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild-type a-synuclein as LB occurs as a hallmark lesion of these disorders, collectively referred to as synucleinopathies, implicating a-synuclein in the pathogenesis of synucleinopathy. To identify modifier genes of a-synuclein-induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg worms) that overexpress human a-synuclein in a pan-neuronal manner. To enhance the RNAi effect in neurons, we crossed a-synuclein Tg worms with an RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to nervous system or synaptic functions, and identified 10 genes that, upon knockdown, caused severe growth/motor abnormalit...

2008-01-01

Conjugation is essential for the anticholestatic effect of NorUrsodeoxycholic acid in taurolithocholic acid induced cholestasis in rat liver

British Library Electronic Table of Contents (United Kingdom)

Abstract NorUDCA (24 norursodeoxycholic acid), the C23 homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine conjugated UDCA (C24) and norUDCA (C23) in isolated perfused rat liver (IPRL) and in natrium/taurocholate cotransporting polypeptide (Ntcp) transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predomi...

2010-01-01

5,8,11,14-Eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3).

In vitro comparison of rat and chicken brain neurotoxic esterase

Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.

1992-01-01

Cadmium inhibits neurogenesis in zebrafish embryonic brain development

A systematic comparison was undertaken to characterize neurotoxic esterase (NTE) from rat and chicken brain in terms of inhibitor sensitivities, pH optima, and molecular weights. Paraoxon titration of phenyl valerate (PV)-hydrolyzing carboxylesterases showed that rat esterases were more sensitive than chicken to paraoxon inhibition at concentrations less than or equal to microM and superimposable with chicken esterases at concentrations of 2.5-1000 microM. Mipafox titration of the paraoxon-resistant esterases at a fixed paraoxon concentration of 100 microM (mipafox concentration: 0-1000 microM) resulted in a mipafox I50 of 7.3 microM for chicken brain NTE and 11.6 microM for rat brain NTE. NTE (i.e., paraoxon-resistant, mipafox-sensitive esterase activity) comprised 80% of chicken and 60% of rat brain paraoxon-resistant activity with the specific activity of chicken brain NTE approximately twice that of rat brain NTE. The pH maxima for NTE from both species was ...

1986-04-01

Lead content of dried films of domestic paints currently sold in Nigeria

Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected ...

2008-05-01

Clinical biochemistry of aluminum

Children are at higher risk from lead exposure because their developing neural system is susceptible to its neurotoxic effects. We studied lead levels of paints manufactured in Nigeria in 2006. Lead levels in 5 colors of paints, each from different manufacturers were measured using flame-atomic absorption spectroscopy. We found that 96% of the paints had higher than recommended levels of lead. The mean lead level of paints ranged from 84.8 to 50,000 ppm, with mean of 14,500 ppm and median of 15,800 ppm. The main determinant of lead levels was color of the paint. As lead levels in paint sold in the past years in Nigeria are likely to be at least as high as that currently sold, it is likely that many existing houses contain dangerously high levels of lead. Efforts need to be undertaken to assess the presence of high lead levels in existing housing and if detected, intervention programs for eliminating risk of exposure should be developed in addition to measures to ...

2007-12-15

Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates

Aluminum toxicity has been implicated in the pathogenesis of a number of clinical disorders in patients with chronic renal failure on long-term intermittent hemodialysis treatment. The predominant disorders have been those involving either bone (osteomalacic dialysis osteodystrophy) or brain (dialysis encephalopathy). In nonuremic patients, an increased brain aluminum concentration has been implicated as a neurotoxic agent in the pathogenesis of Alzheimer's disease and was associated with experimental neurofibrillary degeneration in animals. The brain aluminum concentrations of patients dying with the syndrome of dialysis encephalopathy (dialysis dementia) are significantly higher than in dialyzed patients without the syndrome and in nondialyzed patients. Two potential sources for the increased tissue content of aluminum in patients on hemodialysis have been proposed: (1) intestinal absorption from aluminum containing phosphate-binding gels, and (2) ...

1981-05-01

An argument for the chicken embryo as a model for the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs)

Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional noncholinergic mechanisms ...

2004-07-15

Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

This article will present the argument that the chicken embryo is especially appropriate as an animal model for studying the mechanism of the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs). The PHAHs are a group of toxicologically related compounds including, in part, the polychlorinated dibenzodioxins, dibenzofurans and biphenyls. The chicken (Gallus gallus) embryo is relatively sensitive to the toxicological effects of the PHAHs being approximately two orders of magnitude more sensitive than the mature bird. The chicken embryo has been used to demonstrate general toxicological teratogeneicity, hepatotoxicity and neurotoxicity. Many of these effects, or analogous effects, have also been observed in mammals and fish. Thus, most animals appear to respond to the PHAHs with a similar toxicological profile, indicating that many of the biomarkers used for the PHAHs are valid across a number of species, including the chicken. ...

1996-12-31

Hyaluronic acid production by irradiated human synovial fibroblasts

Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and ?-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest ...

2011-07-23

Effect of drought and abscisic acid application on the osmotic adjustment of four wheat cultivars

Radioactive particles as well as x irradiation from an external source has been used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In order to clarify effects of ionizing irradiation on synovial cells, radioactive gold ("1"9"8Au) and yttrium ("9"0Y) were added to fibroblast cultures derived from human synovial membranes. Other cultures were irradiated by a Picker x-ray machine. Fibroblast growth and hyaluronic acid production were measured. Radioactive gold and yttrium particles induced a significant increase of hyaluronic acid synthesis rate (pg/cell/day) and inhibited fibroblast growth. Fibroblasts continued to overproduce hyaluronic acid and to show growth inhibition 3 weeks after irradiation with radioactive gold. Hydrocortisone inhibited hyaluronic acid overproduction induced by radioactive gold. Overproduction of hyaluronic acid induced by the x-ray machine was inhibited by hydrocortisone, ...

1977-01-01

Chiral salicyloxazolines as auxiliaries for the asymmetric synthesis of ruthenium polypyridyl complexes.

The accumulation of osmolytes in leaf tissues and the abscisic acid-induced stomatal closure are well-recognized mechanisms associated with drought tolerance in crop plants. We determine the response in terms of osmotic potential and the contents of leaf proline, glycine betaine and soluble sugar at booting and grain filling stages of four wheat (Triticum aestivum L.) cultivars to drought and exogenously applied abscisic acid (ABA) in a pot study. Leaf sample were collected 3, 6 and 9 days after drought induction and at 48 and 72 h of re-watering (recovery). Marked decreases in osmotic potential associated with the accumulation of proline, glycine betaine and soluble sugars occurred under conditions of drought stress Accession 011320 was most sensitive to drought and showed the largest decrease in osmotic potential and least accumulation of proline, sugar and glycine betaine The inhibitory effects of drought stress were ameliorated by exogenous application of ABA. ...

2010-02-01

Bip overexpression, but not CHOP inhibition, attenuates fatty-acid-induced endoplasmic reticulum stress and apoptosis in HepG2 liver cells

Chiral auxiliaries are promising emerging tools for the asymmetric synthesis of octahedral metal complexes. We recently introduced chiral salicyloxazolines as coordinating bidentate chiral ligands which provide excellent control over the metal-centered configuration in the course of ligand substitution reactions and can be removed afterward in an acid-induced fashion under complete retention of configuration (J. Am. Chem. Soc. 2009, 131, 9602-9603). Here reported is our detailed investigation of this sequence of reactions, affording virtually enantiopure ruthenium polypyridyl complexes. The control of the metal-centered chirality by the coordinated chiral salicyloxazolinate ligand was evaluated as a function of reaction conditions, the employed bidentate 2,2'-bipyridine and 1,10-phenanthroline ligands, and the substituent at the asymmetric 5-position of the oxazoline heterocycle. Most striking was the strong influence of the reaction solvent, with aprotic solvents ...

2010-09-01

British Library Electronic Table of Contents (United Kingdom)

Aims: In this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis. Main methods: Human liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2. Key findings: Pa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by inc...

2010-01-01

The neurotoxic effects of artemether on the cytoarchitecture of the cerebellum of adult male wistar rats

Sequences, geographic variations and molecular phylogeny of venom phospholipases and threefinger toxins of eastern India Bungarus fasciatus and kinetic analyses of its Pro31 phospholipases A2.

In a 70kg adult man, artemether is given at a total dosage of 480mg for five days in the treatment of malarial. Using t-test analysis technique at 95% confidence interval i.e t < 0.05 and P - value = 2.26, no significant difference was observed between the average brain and cerebellar weight, the average width of cerebellar cortical layers, the density and the average size of Purkinje Cells in the control groups C1 and C2 and the experimental group E. In the present study, there were no gross or morphological differences between the two groups of animals (control and experimental groups) on day 7 at the completion of experimental procedure. A significant statistical increase in average body weight was observed in the control groups C1 (which received only standard diet and water) and C2 (which received 1.23mg/kg body weight of normal saline intramuscularly in addition to standard diet and water) from 140 + 19.65g on day 1 to 146 + 19.90g on day 7 and 151 + 12.0g on day 1 to 156.2 + ...

2007-01-01

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Neurotoxicological effects of cinnabar (a Chinese mineral medicine, HgS) in mice

Eight phospholipases A2 (PLAs) and four three-finger-toxins (3FTx) from the pooled venom of Bungarus fasciatus (Bf) were previously studied and sequenced, but their expression pattern in individual Bf venom and possible geographic variations remained to be investigated. We herein analyze the individual venom of two Bf specimens from Kolkata (designated as KBf) to address this question. Seven PLAs and five 3FTx were purified from the KBf venoms, and respective cDNAs were cloned from venom glands of one of the snakes. Comparison of their mass and N-terminal sequence revealed that all the PLAs were conserved in both KBf venoms, but that two of their 3FTx isoforms were variable. When comparing the sequences of these KBf-PLAs with those published, only one was found to be identical to that of Bf Vb-2, and the other five were 94-98% identical to those of Bf II, III, Va, VI and XI-2, respectively. Notably, the most abundant PLA isoforms of Bf and KBf venoms contain Pro31 substitution. They ...

2006-12-08

The Effects of Surface Chemistry on the Properties of Proteins Confined in Nano-porous Materials

Cinnabar, a naturally occurring mercuric sulfide (HgS), has long been used in combination with traditional Chinese medicine as a sedative for more than 2000 years. Up to date, its pharmacological and toxicological effects are still unclear, especially in clinical low-dose and long-term use. In this study, we attempted to elucidate the effects of cinnabar on the time course of changes in locomotor activities, pentobarbital-induced sleeping time, motor equilibrium performance and neurobiochemical activities in mice during 3- to 11-week administration at a clinical dose of 10 mg/kg/day. The results showed that cinnabar was significantly absorbed by gastrointestinal (G-I) tract and transported to brain tissues. The spontaneous locomotor activities of male mice but not female mice were preferentially suppressed. Moreover, frequencies of jump and stereotype-1 episodes were progressively decreased after 3-week oral administration in male and female mice. Pentobarbital-induced sleeping time ...

2007-10-15

A criterion to determine whether cis-4-hydroxyproline is produced in animal tissues

The entrapment of proteins using the sol-gel route provides a means to retain its native properties and artificially reproduce the molecular crowding and confinement experienced by proteins in the cell allowing investigation of the physico-chemical and structural properties of biomolecules at the biotic/abiotic interface. The biomolecules are spatially separated and 'caged' in the gel structure but solutes can freely permeate the matrix. Thus, properties such as the folding of ensembles of individual molecules can be examined in the absence of aggregation effects that can occur in solution studies. Green fluorescent protein from Aequorea coerulescens was used as a model protein to examine the unfolding/re-folding properties of protein in silica gels. The recombinant protein was isolated and purified from Escherichia coli extracts by cell lysis, three-phase partitioning, dialysis, and anion exchange chromatography. The purity of the protein was greater than 90% as ...

2007-09-01

A criterion to determine whether cis-4-hydroxyproline is produced in animal tissues

Hydrolyzates of tissues that had been labeled with (14C)proline often contain significant amounts of cis-4-hydroxy(14C)proline. Since animal cells do not contain an enzyme which can effect formation of cis-4-hydroxyproline, there are only two possible explanations for its presence. Either it is formed during acid hydrolysis of trans-4-hydroxyproline (which is synthesized by cells and is a common constituent of connective tissues), or it is produced by a nonenzymatic mechanism such as attack by oxygen radicals. It is important to resolve this issue because if a nonenzymatic mechanism is active in connective tissues, then it will be necessary to reevaluate currently accepted ideas about production of hydroxyproline. This communication describes a method for distinguishing between the two alternate explanations. Tissues or cells are labeled with (14C)proline, and then a known amount of trans-4-hydroxy(3H)proline is added to each sample before hydrolysis; the relative amounts of (14C)- and ...

1984-03-01