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Sample records for chronic ethanol exposure

  1. Hepatotoxic potential of combined toluene-chronic ethanol exposure

    Energy Technology Data Exchange (ETDEWEB)

    Howell, S.R.; Christian, J.E.; Isom, G.E.

    1986-05-01

    The hepatoxic properties of concurrent chronic oral ethanol ingestion and acute toluene inhalation were evaluated. Male rats were maintained on ethanol-containing or control liquid diets for 29 days. Animals of each group were subjected to five 20-min exposures to 10 000 ppm toluene with 30 min of room air inhalation between exposures on days 22, 24, 26, and 28 of liquid diet feeding. Some of the ethanol-fed animals were withdrawn from ethanol 14 h before exposure. Ethanol-withdrawn animals displayed an increased sensitivity to the narcotic action of toluene. Animals were sacrificed and assays performed on day 29. Stress markers (plasma corticosterone, free fatty acid, and glucose) were not affected by treatments. A modest elevation in plasma aspartate amino-transferase occurred in non-withdrawn animals receiving both ethanol and toluene. Ethanol-toluene exposure increased both relative liver weight and liver triglycerides. Toluene antagonized the hypertriglyceridemia associated with chronic ethanol ingestion. This study indicates that combined ethanol and toluene exposure has minor potential to induce acute liver injury, but results in altered deposition of hepatic triglycerides.

  2. Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: Mechanisms and reversal by exogenous ACTH

    OpenAIRE

    Boyd, Kevin N.; Kumar, Sandeep; O'Buckley, Todd K.; Morrow, A. Leslie

    2010-01-01

    Acute ethanol administration increases potent GABAergic neuroactive steroids, specifically (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP) and (3α,5α)-3,21-dihydroxypregnan-20-one. In addition, neuroactive steroids contribute to ethanol actions. Chronic ethanol exposure results in tolerance to many effects of ethanol, including ethanol-induced increases in neuroactive steroid levels. To determine the mechanisms of tolerance to ethanol-induced increases in neuroactive steroids, we investigated cri...

  3. Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure

    OpenAIRE

    Lowery-Gionta, Emily G; Marcinkiewcz, Catherine A.; Kash, Thomas L.

    2014-01-01

    Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased a...

  4. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

    Directory of Open Access Journals (Sweden)

    G. Morais-Silva

    2016-01-01

    Full Text Available Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol, but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  5. Chronic ethanol exposure enhances the aggressiveness of breast cancer: the role of p38γ.

    Science.gov (United States)

    Xu, Mei; Wang, Siying; Ren, Zhenhua; Frank, Jacqueline A; Yang, Xiuwei H; Zhang, Zhuo; Ke, Zun-Ji; Shi, Xianglin; Luo, Jia

    2016-01-19

    Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12-48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the scattering of MCF7, BT20 and T47D cell colonies in a 3-dimension culture system. Chronic ethanol exposure also increased colony formation in an anchorage-independent condition and stimulated cell invasion/migration. Chronic ethanol exposure increased cancer stem-like cell (CSC) population by more than 20 folds. Breast cancer cells exposed to ethanol in vitro displayed a much higher growth rate and metastasis in mice. Ethanol selectively activated p38γ MAPK and RhoC but not p38α/β in a concentration-dependent manner. SP-MCF7 cells, a derivative of MCF7 cells which compose mainly CSC expressed high levels of phosphorylated p38γ MAPK. Knocking-down p38γ MAPK blocked ethanol-induced RhoC activation, cell scattering, invasion/migration and ethanol-increased CSC population. Furthermore, knocking-down p38γ MAPK mitigated ethanol-induced tumor growth and metastasis in mice. These results suggest that chronic ethanol exposure can enhance the aggressiveness of breast cancer by activating p38γ MAPK/RhoC pathway. PMID:26655092

  6. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis

    International Nuclear Information System (INIS)

    Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that modulates osteoblastogenesis. In addition, the demonstrated inhibitory effects of chronic ethanol exposure on direct bone formation in rats are hypothetically mediated by TNF-α signaling. The effects in mice are unreported. Therefore, we hypothesized that in mice (1) administration of a soluble TNF receptor 1 derivative (sTNF-R1) would protect direct bone formation during chronic ethanol exposure, and (2) administration of recombinant mouse TNF-α (rmTNF-α) to ethanol naive mice would inhibit direct bone formation. We utilized a unique model of limb lengthening (distraction osteogenesis, DO) combined with liquid diets to measure chronic ethanol's effects on direct bone formation. Chronic ethanol exposure resulted in increased marrow TNF, IL-1, and CYP 2E1 RNA levels in ethanol-treated vs. control mice, while no significant weight differences were noted. Systemic administration of sTNF-R1 during DO (8.0 mg/kg/2 days) to chronic ethanol-exposed mice resulted in enhanced direct bone formation as measured radiologically and histologically. Systemic rmTNF-α (10 μg/kg/day) administration decreased direct bone formation measures, while no significant weight differences were noted. We conclude that chronic ethanol-associated inhibition of direct bone formation is mediated to a significant extent by the TNF signaling axis in a mouse model

  7. Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring

    Directory of Open Access Journals (Sweden)

    Fei Liang

    2015-01-01

    Full Text Available Although paternal ethanol (EtOH abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well-documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg−1 were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9 in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS.

  8. Lactobacillus rhamnosus GG Effect on Behavior of Zebrafish During Chronic Ethanol Exposure.

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    Schneider, Ana Claudia Reis; Rico, Eduardo Pacheco; de Oliveira, Diogo Losch; Rosemberg, Denis Broock; Guizzo, Ranieli; Meurer, Fábio; da Silveira, Themis Reverbel

    2016-01-01

    Ethanol is a widely consumed drug, which acts on the central nervous system to induce behavioral alterations ranging from disinhibition to sedation. Recent studies have produced accumulating evidence for the therapeutic role of probiotic bacteria in behavior. We aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) on the behavior of adult zebrafish chronically exposed to ethanol. Adult wild-type zebrafish were randomly divided into four groups, each containing 15 fish. The following groups were formed: Control (C), received unsupplemented feed during the trial period; Probiotic (P), fed with feed supplemented with LGG; Ethanol (E), received unsupplemented feed and 0.5% of ethanol directly added to the tank water; and Probiotic+Ethanol (P+E), group under ethanol exposure (0.5%) and fed with LGG supplemented feed. After 2 weeks of exposure, the novel tank test was used to evaluate fish behavior, which was analyzed using computer-aided video tracking. LGG alone did not alter swimming behavior of the fish. Ethanol exposure led to robust behavioral effects in the form of reduced anxiety levels, as indicated by increased vertical exploration and more time spent in the upper region of the novel tank. The group exposed to ethanol and treated with LGG behaved similarly to animals exposed to ethanol alone. Taken together, these results show that zebrafish behavior was not altered by LGG per se, as seen in murine models. This was the first study to investigate the effects of a probiotic diet on behavior after a chronic ethanol exposure. PMID:26862467

  9. Acute and chronic ethanol exposure differentially affect induction of hippocampal LTP.

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    Fujii, Satoshi; Yamazaki, Yoshihiko; Sugihara, Toshimichi; Wakabayashi, Ichiro

    2008-05-23

    Using hippocampal slices, we found that chronic ethanol consumption by rats induces tolerance to the impairing effects of acute ethanol treatment on induction of long-term potentiation (LTP) in CA1 neurons. In hippocampal slices from pair-fed control rats, stable LTP was induced by tetanic stimulation consisting of 25 or more pulses at 100 Hz, but not by tetanic stimulation of 15 pulses at 100 Hz, and LTP induction was blocked if the tetanus was delivered in the presence of 8.6 mM ethanol, 1 microM muscimol, a gamma-aminobutyric acid (GABA) A receptor agonist, or 2.5 microM dl-2-amino-5-phosphonovaleric acid (AP5), an N-methyl-d-aspartate (NMDA) receptor antagonist. In hippocampal slices from rats chronically fed a liquid diet containing ethanol, a tetanus consisting of 15 pulses at 100 Hz did induce stable LTP, indicating a decrease in the stimulation threshold for inducing LTP. Application of ethanol, muscimol, or AP5 did not affect LTP induction in these cells, suggesting that the effects of chronic ethanol exposure on LTP induction are mediated by a reduction in GABAergic inhibition or an increase in NMDA receptor activity in hippocampal CA1 neurons. PMID:18423576

  10. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    Science.gov (United States)

    Robinson, Stacey L; Alexander, Nancy J; Bluett, Rebecca J; Patel, Sachin; McCool, Brian A

    2016-09-01

    The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol. PMID:26707595

  11. Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task.

    Directory of Open Access Journals (Sweden)

    Shawn K Acheson

    Full Text Available Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0 g/kg 30 min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0 g/kg for 16 days (PND30 To PND46 prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.

  12. Chronic intermittent ethanol exposure and withdrawal leads to adaptations in nucleus accumbens core postsynaptic density proteome and dendritic spines.

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    Uys, Joachim D; McGuier, Natalie S; Gass, Justin T; Griffin, William C; Ball, Lauren E; Mulholland, Patrick J

    2016-05-01

    Alcohol use disorder is a chronic relapsing brain disease characterized by the loss of ability to control alcohol (ethanol) intake despite knowledge of detrimental health or personal consequences. Clinical and pre-clinical models provide strong evidence for chronic ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the nucleus accumbens (NAc). However, the neural mechanisms that contribute to aberrant glutamatergic signaling in ethanol-dependent individuals in this critical brain structure remain unknown. Using an unbiased proteomic approach, we investigated the effects of chronic intermittent ethanol (CIE) exposure on neuroadaptations in postsynaptic density (PSD)-enriched proteins in the NAc of ethanol-dependent mice. Compared with controls, CIE exposure significantly changed expression levels of 50 proteins in the PSD-enriched fraction. Systems biology and functional annotation analyses demonstrated that the dysregulated proteins are expressed at tetrapartite synapses and critically regulate cellular morphology. To confirm this latter finding, the density and morphology of dendritic spines were examined in the NAc core of ethanol-dependent mice. We found that CIE exposure and withdrawal differentially altered dendrite diameter and dendritic spine density and morphology. Through the use of quantitative proteomics and functional annotation, these series of experiments demonstrate that ethanol dependence produces neuroadaptations in proteins that modify dendritic spine morphology. In addition, these studies identified novel PSD-related proteins that contribute to the neurobiological mechanisms of ethanol dependence that drive maladaptive structural plasticity of NAc neurons. PMID:25787124

  13. Chronic cocaine or ethanol exposure during adolescence alters novelty-related behaviors in adulthood.

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    Stansfield, Kirstie H; Kirstein, Cheryl L

    2007-04-01

    Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency and drug use at this time is associated with an increased risk. Human adolescents are predisposed toward an increased likelihood of risk-taking behaviors [Zuckerman M. Sensation seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr 1986;74:59-70.], including drug use or initiation. In the present study, adolescent animals were exposed to twenty days of either saline (0.9% sodium chloride), cocaine (20 mg/kg) or ethanol (1 g/kg) i.p. followed by a fifteen-day washout period. All animals were tested as adults on several behavioral measures including locomotor activity induced by a novel environment, time spent in the center of an open field, novelty preference and novel object exploration. Animals exposed to cocaine during adolescence and tested as adults exhibited a greater locomotor response in a novel environment, spent less time in the center of the novel open field and spent less time with a novel object, results that are indicative of a stress or anxiogenic response to novelty or a novel situation. Adolescent animals chronically administered ethanol and tested as adults, unlike cocaine-exposed were not different from controls in a novel environment, indicated by locomotor activity or time spent with a novel object. However, ethanol-exposed animals approached the novel object more, suggesting that exposure to ethanol during development may result in less-inhibited behaviors during adulthood. The differences in adult behavioral responses after drug exposure during adolescence are likely due to differences in the mechanisms of action of the drugs and subsequent reward and/or stress responsivity. Future studies are needed to determine the neural substrates of these long lasting drug-induced changes. PMID

  14. Chronic ethanol exposure downregulates hepatic expression of pregnane X receptor and P450 3A11 in female ICR mice

    International Nuclear Information System (INIS)

    Pregnane X receptor (PXR) is a nuclear receptor that regulates cytochrome P450 3A (CYP3A) gene transcription in a ligand-dependent manner. Ethanol has been reported to be either an inducer or an inhibitor of CYP3A expression. In this study, we investigated the effects of chronic ethanol exposure on PXR and P450 3A11 gene expression in mouse liver. Female ICR mice were administered by gavage with different doses (1000, 2000 and 4000 mg/kg) of ethanol for up to 5 weeks. Hepatic PXR and P450 3A11 mRNA levels were measured using RT-PCR. Erythromycin N-demethylase (ERND) activity was used as an indicator of CYP3A protein expression. Results showed that chronic ethanol exposure markedly decreased hepatic PXR and P450 3A11 mRNA levels. Consistent with downregulation of P450 3A11 mRNA, chronic ethanol exposure significantly decreased ERND activity in a dose-dependent manner. Additional experiment showed that chronic ethanol exposure significantly increased plasma endotoxin level and hepatic CD14 and TLR-4 mRNA expression, all of which were blocked by elimination of Gram-negative bacteria and endotoxin with antibiotics. Correspondingly, pretreatment with antibiotics reversed the downregulation of PXR and P450 3A11 mRNA expression and ERND activity in mouse liver. Furthermore, the downregulation of hepatic PXR and P450 3A11 mRNA expression was significantly attenuated in mice pretreated with GdCl3, a selective Kupffer cell toxicant. GdCl3 pretreatment also significantly attenuated chronically ethanol-induced decrease in ERND activity. These results indicated that activation of Kupffer cells by gut-derived endotoxin contributes to downregulation of hepatic PXR and P450 3A11 expression during chronic alcohol intoxication

  15. Ethanol withdrawal is required to produce persisting N-methyl-D-aspartate receptor-dependent hippocampal cytotoxicity during chronic intermittent ethanol exposure.

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    Reynolds, Anna R; Berry, Jennifer N; Sharrett-Field, Lynda; Prendergast, Mark A

    2015-05-01

    Chronic intermittent ethanol consumption is associated with neurodegeneration and cognitive deficits in preclinical laboratory animals and in the clinical population. While previous work suggests a role for neuroadaptations in the N-methyl-d-aspartate (NMDA) receptor in the development of ethanol dependence and manifestation of withdrawal, the relative roles of ethanol exposure and ethanol withdrawal in producing these effects have not been fully characterized. To examine underlying cytotoxic mechanisms associated with chronic intermittent ethanol (CIE) exposure, organotypic hippocampal slices were exposed to 1-3 cycles of ethanol (50 mM) in cell culture medium for 5 days, followed by 24 h of ethanol withdrawal, in which a portion of slices were exposed to competitive NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV; 40 μM). Cytotoxicity was assessed using immunohistochemical labeling of neuron-specific nuclear protein (NeuN; Fox-3), a marker of mature neurons, and thionine (2%) staining of Nissl bodies. Multiple cycles of CIE produced neurotoxicity, as reflected in persisting losses of neuron NeuN immunoreactivity and thionine staining in each of the primary cell layers of the hippocampal formation. Hippocampi aged in vitro were significantly more sensitive to the toxic effects of multiple cycles of CIE than were non-aged hippocampi. This effect was not demonstrated in slices exposed to continuous ethanol, in the absence of withdrawal, or to a single exposure/withdrawal regimen. Exposure to APV significantly attenuated the cytotoxicity observed in the primary cell layers of the hippocampus. The present findings suggest that ethanol withdrawal is required to produce NMDA receptor-dependent hippocampal cytotoxicity, particularly in the aging hippocampus in vitro. PMID:25746220

  16. A novel mouse model for the study of the inhibitory effects of chronic ethanol exposure on direct bone formation

    Science.gov (United States)

    Excessive alcohol consumption has been reported to interfere with human bone homeostasis and repair in multiple ways. Previous studies have demonstrated that chronic ethanol exposure in the rat via an intragastric dietary delivery system inhibits direct bone formation during distraction osteogenesis...

  17. In vivo chronic intermittent ethanol exposure reverses the polarity of synaptic plasticity in the nucleus accumbens shell.

    Science.gov (United States)

    Jeanes, Zachary M; Buske, Tavanna R; Morrisett, Richard A

    2011-01-01

    Glutamatergic synaptic plasticity in the nucleus accumbens (NAc) is implicated in response to sensitization to psychomotor-stimulating agents, yet ethanol effects here are undefined. We studied the acute in vitro and in vivo effects of ethanol in medium spiny neurons from the shell NAc subregion of slices of C57BL/6 mice by using whole-cell voltage-clamp recordings of α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) excitatory postsynaptic current (EPSCs). Synaptic conditioning (low-frequency stimulation with concurrent postsynaptic depolarization) reliably depressed AMPA EPSCs by nearly 30%; this accumbal long-term depression (LTD) was blocked by a nonselective N-methyl-D-aspartate (NMDA) receptor antagonist (DL-2-amino-5-phosphonovaleric acid) and a selective NMDA receptor 2B antagonist [R-(R*,S*)-α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidine propanol]. Acute ethanol exposure inhibited the depression of AMPA EPSCs differentially with increasing concentrations, but this inhibitory action of ethanol was occluded by a D1-selective dopamine receptor agonist. Ethanol dependence was elicited in C57BL/6 mice by two separate 4-day bouts of chronic intermittent ethanol (CIE) vapor exposure. When assessed 24 h after a single bout of in vivo CIE vapor exposure, NAc LTD was absent, and instead NMDA receptor-dependent synaptic potentiation [long-term potentiation (LTP)] was reliably observed. It is noteworthy that both LTP and LTD were completely absent after an extended withdrawal (72 h) after a single 3-day CIE vapor bout. These observations demonstrate that 1) accumbal synaptic depression is mediated by NR2B receptors, 2) accumbal synaptic depression is highly sensitive to both acute and chronic ethanol exposure, and 3) alterations in this synaptic process may constitute a neural adaptation that contributes to the induction and/or expression of ethanol dependence. PMID:20947635

  18. A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats

    OpenAIRE

    Aroor Annayya R; Roy Lowery J; Restrepo Ricardo J; Mooney Brian P; Shukla Shivendra D

    2012-01-01

    Abstract Background Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol- binge were compared. Results The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-bi...

  19. Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol.

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    Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

    2016-03-01

    Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after-hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID:26286839

  20. Effects of chronic prenatal ethanol exposure on locomotor activity, and hippocampal weight, neurons, and nitric oxide synthase activity of the young postnatal guinea pig.

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    Gibson, M A; Butters, N S; Reynolds, J N; Brien, J F

    2000-01-01

    Decreased nitric oxide synthase (NOS)-catalyzed formation of NO from L-arginine may be involved in ethanol teratogenesis involving the hippocampus. This hypothesis was tested by determining the effects of chronic prenatal ethanol exposure on locomotor activity and on hippocampal weight, number of CA1 and CA3 pyramidal cells and dentate gyrus granule cells, and NOS activity of the postnatal guinea pig. Timed, pregnant guinea pigs received one of the following chronic oral regimens throughout gestation: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding, or water. At postnatal day (PD) 10, spontaneous locomotor activity was measured. At PD 12, histological analysis was performed on the hippocampal formation, in which hippocampal CA1 and CA3 pyramidal cells and dentate gyrus granule cells were counted; body, brain, and hippocampal weights were measured; and hippocampal NOS enzymatic activity was determined using a radiometric assay. Chronic prenatal ethanol exposure produced hyperactivity, decreased the brain and hippocampal weights with no change in body weight, decreased the number of hippocampal CA1 pyramidal cells by 25-30%, and had no effect on hippocampal NOS activity compared with the two control groups. These data, together with our previous findings in the fetal guinea pig, demonstrate that chronic prenatal ethanol exposure decreases hippocampal NOS activity in near-term fetal life that temporally precedes the selective loss of hippocampal CA1 pyramidal cells in postnatal life. PMID:10758347

  1. Effects of chronic exposure to ethanol on the physical and functional properties of the plasma membrane of S49 lymphoma cells

    International Nuclear Information System (INIS)

    The effects of chronic exposure to ethanol on the physical and functional properties of the plasma membrane were examined with cultured S49 lymphoma cells. The β-adrenergic receptor-coupled adenylate cyclase system was used as a probe of the functional properties of the plasma membrane. Steady-state fluorescence anisotropy of diphenylhexatriene and the lipid composition of the plasma membrane were used as probes of the physical properties of the membrane. Cells were grown under conditions such that the concentration of ethanol in the growth medium remained stable and oxidation of ethanol to acetaldehyde was not detected. Chronic exposure of S49 cells to 50 mM ethanol or growth of cells at elevated temperature resulted in a decrease in adenylate cyclase activity. There were no changes in the density of receptors or in the affinity of β-adrenergic receptors for agonists or antagonists following chronic exposure to ethanol. The fluorescence anisotropy of diphenylhexatriene was lower in plasma membranes prepared from cells that had been treated with 50 mM ethanol than in membranes prepared from control cells. However, this change was not associated with changes in the fatty acid composition or the cholesterol to phospholipid ratio of the plasma membrane. There was a small but statistically significant decrease in the amount of phosphatidylserine and an increase in the amount of phosphatidylethanolamine. These changes cannot account for the decrease in anisotropy. In contrast to the effect of ethanol, a decrease in adenylate cyclase activity following growth of S49 cells at 400C was not associated with a change in anisotropy

  2. Sex Differences in Caffeine Neurotoxicity Following Chronic Ethanol Exposure and Withdrawal

    OpenAIRE

    Butler, Tracy R.; Smith, Katherine J.; Berry, Jennifer N.; Sharrett-Field, Lynda J.; Prendergast, Mark A.

    2009-01-01

    Aims: Caffeine is a central nervous system stimulant that produces its primary effects via antagonism of the A1 and A2A adenosine receptor subtypes. Previous work demonstrated a sex difference in neurotoxicity produced by specific adenosine A1 receptor antagonism during ethanol withdrawal (EWD) in vitro that was attributable to effects downstream of A1 receptors at NMDA receptors. The current studies were designed to examine the effect of non-specific adenosine receptor antagonism with caffei...

  3. Effect of chronic prenatal ethanol exposure on nitric oxide synthase I and III proteins in the hippocampus of the near-term fetal guinea pig.

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    Kimura, K A; Chiu, J; Reynolds, J N; Brien, J F

    1999-01-01

    Chronic prenatal ethanol exposure suppresses nitric oxide synthase (NOS) enzymatic activity, in the hippocampus of the near-term fetal guinea pig at gestational day (GD) 62. The objective of this study was to determine if this decrease in NOS activity is the result of decreased NOS I and NOS III protein expression. Pregnant guinea pigs received oral administration of 4 g ethanol/kg maternal body weight/day (n = 8), isocaloric-sucrose/pair feeding (n = 8), or water (n = 8) from GD 2 to GD 61. The NOS I and NOS III protein expression and localization in the hippocampus were determined using Western blot analysis and immunohistochemistry, respectively. The chronic ethanol regimen produced fetal body, brain, and hippocampal growth restriction compared with the isocaloric-sucrose/pair fed and water groups but did not affect the expression or localization of NOS I and NOS III proteins in the hippocampus. The decrease in NOS enzymatic activity induced by chronic prenatal ethanol exposure may be the result of posttranslational modification of NOS I and/or NOS III protein in the hippocampus of the near-term fetal guinea pig. PMID:10386828

  4. Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure

    Science.gov (United States)

    Rose, Jamie H.; Karkhanis, Anushree N.; Steiniger-Brach, Björn; Jones, Sara R.

    2016-01-01

    The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc) κ opioid receptors (KOR) in chronic intermittent ethanol (CIE) exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs. PMID:27472317

  5. Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure

    Directory of Open Access Journals (Sweden)

    Jamie H. Rose

    2016-07-01

    Full Text Available The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc κ opioid receptors (KOR in chronic intermittent ethanol (CIE exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs. However, the effects of nalmefene on accumbal dopamine transmission and KOR function are poorly understood. We investigated the effects of nalmefene on dopamine transmission and KORs using fast scan cyclic voltammetry in NAc brain slices from male C57BL/6J mice following five weeks of CIE or air exposure. Nalmefene concentration-dependently reduced dopamine release similarly in air and CIE groups, suggesting that dynorphin tone may not be present in brain slices. Further, nalmefene attenuated dopamine uptake rates to a greater extent in brain slices from CIE-exposed mice, suggesting that dopamine transporter-KOR interactions may be fundamentally altered following CIE. Additionally, nalmefene reversed the dopamine-decreasing effects of a maximal concentration of a KOR agonist selectively in brain slices of CIE-exposed mice. It is possible that nalmefene may attenuate withdrawal-induced increases in ethanol consumption by modulation of dopamine transmission through KORs.

  6. Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol

    Science.gov (United States)

    Lopez, M. F.; Becker, H. C.; Chandler, L. J.

    2014-01-01

    Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol. PMID:25266936

  7. In Vivo Chronic Intermittent Ethanol Exposure Reverses the Polarity of Synaptic Plasticity in the Nucleus Accumbens Shell

    OpenAIRE

    Jeanes, Zachary M.; Buske, Tavanna R.; Morrisett, Richard A.

    2011-01-01

    Glutamatergic synaptic plasticity in the nucleus accumbens (NAc) is implicated in response to sensitization to psychomotor-stimulating agents, yet ethanol effects here are undefined. We studied the acute in vitro and in vivo effects of ethanol in medium spiny neurons from the shell NAc subregion of slices of C57BL/6 mice by using whole-cell voltage-clamp recordings of α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) excitatory postsynaptic current (EPSCs). Synaptic conditioning (l...

  8. Toxicity of prolonged exposure to ethanol and gasoline autoengine exhaust gases

    Energy Technology Data Exchange (ETDEWEB)

    Massad, E.; Saldiva, P.H.; Saldiva, C.D.; Caldeira, M.P.; Cardoso, L.M.; de Morais, A.M.; Calheiros, D.F.; da Silva, R.; Boehm, G.M.

    1986-08-01

    A comparative chronic inhalation exposure study was performed to investigate the potential health effects of gasoline and ethanol engine exhaust fumes. Test atmospheres of gasoline and ethanol exhaust were given to Wistar rats and Balb C mice housed in inhalation chambers for a period of 5 weeks. Gas concentration and physical parameters were continually monitored during the exposure period. Several biological parameters were assessed after the exposure including pulmonary function, mutagenicity, and hematological, biochemical, and morphological examinations. The results demonstrated that the chronic toxicity of the gasoline-fueled engine is significantly higher than that of the ethanol engine.

  9. Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption

    OpenAIRE

    Smith, Maren L.; Lopez, Marcelo F; Archer, Kellie J; Wolen, Aaron R.; Howard C Becker; Miles, Michael F.

    2016-01-01

    Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive eth...

  10. Histopathological and imaging modifications in chronic ethanolic encephalopathy.

    Science.gov (United States)

    Folescu, Roxana; Zamfir, Carmen Lăcrămioara; Sişu, Alina Maria; Motoc, Andrei Gheorghe Marius; Ilie, Adrian Cosmin; Moise, Marius

    2014-01-01

    Chronic abuse of alcohol triggers different types of brain damage. The Wernicke-Korsakoff syndrome gets together Wernicke's encephalopathy and Korsakoff's syndrome. Another type of encephalopathy associated with chronic ethanol consumption is represented by the Marchiafava-Bignami malady or syndrome, an extremely rare neurological disorder, which is characterized by a demielinization of corpus callosum, extending as far as a necrosis. Because the frequency of ethanolic encephalopathy is increased and plays a major role in the sudden death of ethanolic patients, we have studied the chronic ethanolic encephalopathy both in deceased and in living patients, presenting different pathologies related to the chronic ethanol consumption. The present study investigated the effects of chronic ethanolic encephalopathy on the central nervous system based both on the histopathological exam of the tissular samples and the imaging investigation, such as MRI and CT. PMID:25329105

  11. Gestational Exposure to Inhaled Vapors of Ethanol and Gasoline-Ethanol Blends in Rats

    Science.gov (United States)

    The US automotive fleet is powered primarily by gasoline-ethanol fuel blends containing up to 10% ethanol (ElO). Uncertainties regarding the health risks associated with exposure to ElO prompted assessment of the effects of prenatal exposure to inhaled vapors of gasoline-ethanol ...

  12. Chronic Ethanol Feeding Suppresses β-Adrenergic Receptor-Stimulated Lipolysis in Adipocytes Isolated from Epididymal Fat

    OpenAIRE

    Kang, Li; Nagy, Laura E.

    2006-01-01

    Chronic ethanol consumption disrupts G protein-dependent signaling pathways in rat adipocytes. Because lipolysis in adipocytes is regulated by G protein-mediated cAMP signal transduction, we hypothesized that cAMP-regulated lipolysis may be vulnerable to long-term ethanol exposure. Male Wistar rats were fed a liquid diet containing ethanol as 35% of total calories or pair-fed a control diet that isocalorically substituted maltose dextrins for ethanol for 4 wk. Lipolysis was measured by glycer...

  13. PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT

    OpenAIRE

    Ricardo M. Pautassi; Nizhnikov, Michael E.; Norman E. Spear; Molina, Juan C.

    2012-01-01

    Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditione...

  14. PRENATAL EXPOSURE TO ETHANOL AFFECTS POSTNATAL NEUROGENESIS IN THALAMUS

    OpenAIRE

    Mooney, Sandra M.; Miller, Michael W.

    2010-01-01

    The number of neurons in the ventrobasal thalamus (VB) in the adolescent rat is unaffected by prenatal exposure to ethanol. This is in sharp contrast to other parts of the trigeminal-somatosensory system which exhibit 30–35% fewer neurons after prenatal ethanol exposure. The present study tested the hypothesis that prenatal ethanol exposure affects dynamic changes in the numbers of VB neurons; such changes reflect the sum of cell proliferation and death. Neuronal number in the VB was determin...

  15. Binge ethanol exposure in late gestation induces ethanol aversion in the dam but enhances ethanol intake in the offspring and affects their postnatal learning about ethanol

    OpenAIRE

    Chotro, M. Gabriela; Arias, Carlos; Norman E. Spear

    2009-01-01

    Previous studies show that exposure to 1 or 2 g/kg ethanol during the last days of gestation increases ethanol acceptance in infant rats. We tested whether prenatal exposure to 3 g/kg, a relatively high ethanol dose, generates an aversion to ethanol in both the dam and offspring, and whether this prenatal experience affects the expression of learning derived from ethanol exposure postnatally. The answer was uncertain, since postnatal administration of a 3 g/kg ethanol dose induces an aversion...

  16. Chronic ethanol treatment potientials ethanol-induced increases in interstitial nucleus accumbens endocannabinoid levels in rats

    OpenAIRE

    Alvarez-Jaimes, Lily; Stouffer, David G.; Parsons, Loren H

    2009-01-01

    We employed in vivo microdialysis to characterize the effect of an ethanol challenge injection on endocannabinoid levels in the nucleus accumbens of ethanol-naïve and chronic ethanol-treated rats. Ethanol (0.75 and 2 g/kg, i.p.) dose-dependently increased dialysate 2-arachidonoylglycerol (to a maximum 157 ± 20% of baseline) and decreased anandamide (to a minimum 52 ± 9% of baseline) in ethanol-naïve rats. The endocannabinoid clearance inhibitor N-(4-hydrophenyl) arachidonoylamide (AM404; 3 mg...

  17. Social consequences of ethanol: Impact of age, stress, and prior history of ethanol exposure.

    Science.gov (United States)

    Varlinskaya, Elena I; Spear, Linda P

    2015-09-01

    The adolescent period is associated with high significance of interactions with peers, high frequency of stressful situations, and high rates of alcohol use. At least two desired effects of alcohol that may contribute to heavy and problematic drinking during adolescence are its abilities to both facilitate interactions with peers and to alleviate anxiety, perhaps especially anxiety seen in social contexts. Ethanol-induced social facilitation can be seen using a simple model of adolescence in the rat, with normal adolescents, but not their more mature counterparts, demonstrating this ethanol-related social facilitation. Prior repeated stress induces expression of ethanol-induced social facilitation in adults and further enhances socially facilitating effects of ethanol among adolescent rats. In contrast, under normal circumstances, adolescent rats are less sensitive than adults to the social inhibition induced by higher ethanol doses and are insensitive to the socially anxiolytic effects of ethanol. Sensitivity to the socially anxiolytic effects of ethanol can be modified by prior stress or ethanol exposure at both ages. Shortly following repeated restraint or ethanol exposure, adolescents exhibit social anxiety-like behavior, indexed by reduced social preference, and enhanced sensitivity to the socially anxiolytic effects of ethanol, indexed through ethanol-associated reinstatement of social preference in these adolescents. Repeated restraint, but not repeated ethanol, induces similar effects in adults as well, eliciting social anxiety-like behavior and increasing their sensitivity to the socially anxiolytic effects of acute ethanol; the stressor also decreases sensitivity of adults to ethanol-induced social inhibition. The persisting consequences of early adolescent ethanol exposure differ from its immediate consequences, with males exposed early in adolescence, but not females or those exposed later in adolescence, showing social anxiety-like behavior when tested

  18. Cytologic alterations in the oral mucosa after chronic exposure to ethanol Alterações citológicas na mucosa bucal após exposição crônica ao etanol

    Directory of Open Access Journals (Sweden)

    Sílvia Regina de Almeida Reis

    2006-04-01

    Full Text Available The effects of ethanol alone on the oral mucosa are still poorly understood, especially because there are few non-smoking chronic consumers of alcoholic beverages. The aim of this study was to evaluate the frequency of micronucleus, abnormal nucleus/cytoplasm ratio, pyknosis, karyorrhexis and karyolysis in exfoliated cells from the buccal mucosa and from the lateral border of the tongue in 36 non-smoker alcoholics (ethanol group and 18 non-smokers and non-drinkers (control group. The Papanicolaou method was used. Since alcoholics generally have hepatobiliary involvement, the association between serum gamma-glutamyl transpeptidase (GGT and some of the analyzed oral mucosa alterations was also investigated. The ethanol group showed a significant increase in the frequency of all alterations analyzed in the tongue cells when compared with the control group (p 0.05; Mann-Whitney. In the ethanol group, the correlation between serum GGT and the frequency of micronucleus and abnormal nucleus/cytoplasm ratio in oral mucosa cells was not significant (p > 0.05; Spearman. In conclusion, chronic exposure to ethanol may be associated with carcinogenic cytologic changes in the oral mucosa, even in the absence of tobacco smoking. These alterations were not correlated with hepatobiliary injury.Os efeitos do etanol isoladamente sobre a mucosa bucal permanecem pouco esclarecidos, sobretudo devido ao baixo número de não-fumantes consumidores crônicos de bebidas alcoólicas. O objetivo deste estudo foi avaliar as freqüências de micronúcleo, relação núcleo/citoplasma anormal, picnose, cariorrexe e cariólise em células esfoliadas da mucosa jugal e do bordo lateral da língua de 36 alcoólatras não-fumantes (grupo etanol e 18 abstêmios de álcool e fumo (grupo controle. O método de Papanicolaou foi utilizado. Uma vez que indivíduos alcoólatras geralmente apresentam comprometimento hepatobiliar, a associação entre gama-glutamil transpeptidase (GGT s

  19. Assessment of Expression of Genes Coding GABAA Receptors during Chronic and Acute Intoxication of Laboratory Rats with Ethanol.

    Science.gov (United States)

    Osechkina, N S; Ivanov, M B; Nazarov, G V; Batotsyrenova, E G; Lapina, N V; Babkin, A V; Berdinskikh, I S; Melekhova, A S; Voitsekhovich, K O; Lisitskii, D S; Kashina, T V

    2016-02-01

    Expression of genes encoding the individual subunits of ionotropic GABAA receptor was assessed after acute and chronic intoxication of rats with ethanol. The chronic 1-month-long exposure to ethanol signifi cantly decreased (by 38%) expression of Gabrb1 gene in the hippocampus. Acute exposure to ethanol elevated expression of genes Gabrb1 (by 1.7 times), Gabra1 (by 3.8 times), and Gabra4 (by 6.5 times), although it diminished expression of Gabra2 gene by 1.4 times. In preliminarily alcoholized rats, acute intoxication with ethanol enhanced expression of genes Gabrb1 and Gabra5 by 1.7 and 8.7 times, respectively. There was neither acute nor chronic effect of ethanol on expression of gene Gabra3. PMID:26902358

  20. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

    Directory of Open Access Journals (Sweden)

    Jessica Godfrey

    Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

  1. Chronic ethanol feeding modulates the synthesis of digestive enzymes

    International Nuclear Information System (INIS)

    The effects of chronic ethanol feeding on pancreatic protein synthesis were investigated. Protein synthesis was assessed by studying the rate of incorporation of 3H-leucine into TCA-precipitable proteins in isolated pancreatic acini from rats. Chronic ethanol ingestion increased the rate of pancreatic protein synthesis by 2-4 fold. The onset of the increase in protein synthesis was detectable two days after ethanol feeding, reached a maximum after 7 days and remained unchanged after 4 months on the ethanol-containing diet. The rate of synthesis of individual digestive enzymes was studied by SDS-PAGE on extracts obtained from purified zymogen granules. Ethanol feeding induced an increase in the rate of synthesis of most of the digestive enzymes; chymotrypsinogen, trypsinogen and an unidentified protein were increased to a greater extent than other digestive enzymes. By contrast, the synthesis of amylase was selectively decreased after ethanol feeding. These results suggest that chronic ethanol ingestion has specific effects on the rate of synthesis of individual digestive enzymes in the exocrine pancreas

  2. Chronic Ethanol Feeding to Rats Decreases Adiponectin Secretion by Subcutaneous Adipocytes

    OpenAIRE

    Chen, Xiaocong; Sebastian, Becky M.; Nagy, Laura E.

    2006-01-01

    Chronic ethanol feeding to mice and rats decreases serum adiponectin concentration and adiponectin treatment attenuates chronic ethanol-induced liver injury. While it is clear that lowered adiponectin has pathophysiological importance, the mechanisms by which chronic ethanol decreases adiponectin are not known. Here we have investigated the impact of chronic ethanol feeding on adiponectin expression and secretion by adipose tissue. Rats were fed a 36% Lieber-DeCarli ethanol-containing liquid ...

  3. Life-Stage PBPK Models for Multiple Routes of Ethanol Exposure in the Rat

    Science.gov (United States)

    Ethanol is commonly blended with gasoline (10% ethanol) in the US, and higher ethanol concentrations are being considered. While the pharmacokinetics and toxicity of orally-ingested ethanol are widely reported, comparable work is limited for inhalation exposure (IE), particularly...

  4. Angiogenesis is repressed by ethanol exposure during chick embryonic development.

    Science.gov (United States)

    Wang, Guang; Zhong, Shan; Zhang, Shi-Yao; Ma, Zheng-Lai; Chen, Jian-Long; Lu, Wen-Hui; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Lu, Da-Xiang; Yang, Xuesong

    2016-05-01

    It is now known that excess alcohol consumption during pregnancy can cause fetal alcohol syndrome to develop. However, it is not known whether excess ethanol exposure could directly affect angiogenesis in the embryo or angiogenesis being indirectly affected because of ethanol-induced fetal alcohol syndrome. Using the chick yolk sac membrane (YSM) model, we demonstrated that ethanol exposure dramatically inhibited angiogenesis in the YSM of 9-day-old chick embryos, in a dose-dependent manner. Likewise, the anti-angiogenesis effect of ethanol could be seen in the developing vessel plexus (at the same extra-embryonic regions) during earlier stages of embryo development. The anti-angiogenic effect of ethanol was found associated with excess reactive oxygen species (ROS) production; as glutathione peroxidase activity increased while superoxide dismutase 1 and 2 activities decreased in the YSMs. We further validated this observation by exposing chick embryos to 2,2'-azobis-amidinopropane dihydrochloride (a ROS inducer) and obtained a similar anti-angiogenesis effect as ethanol treatment. Semiquantitative reverse transcription-polymerase chain reaction analysis of the experimental YSMs revealed that expression of angiogenesis-related genes, vascular endothelial growth factor and its receptor, fibroblast growth factor 2 and hypoxia-inducible factor, were all repressed following ethanol and 2,2'-azobis-amidinopropane dihydrochloride treatment. In summary, our results suggest that excess ethanol exposure inhibits embryonic angiogenesis through promoting superfluous ROS production during embryo development. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26177723

  5. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

    OpenAIRE

    Bahi, Amine; Dreyer, Jean-luc

    2014-01-01

    Objective: Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP.Methods: Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were s...

  6. PRENATAL ETHANOL EXPOSURE INCREASES ETHANOL INTAKE AND REDUCES C-FOS EXPRESSION IN INFRALIMBIC CORTEX OF ADOLESCENT RATS

    OpenAIRE

    Fabio, Maria Carolina; March, Samanta M.; Molina, Juan Carlos; Nizhnikov, Michael E.; Norman E. Spear; Pautassi, Ricardo Marcos

    2012-01-01

    Prenatal ethanol exposure significantly increases later predisposition for alcohol intake, but the mechanisms associated with this phenomenon remain hypothetical. This study analyzed (Exp. 1) ethanol intake in adolescent inbred WKAH/Hok Wistar rats prenatally exposed to ethanol (2.0 g/kg) or vehicle, on gestational days 17–20. Subsequent Experiments (2, 3 and 4) tested several variables likely to underlie the effect of gestational ethanol on adolescent ethanol preference, including ethanol-in...

  7. Chronic ethanol consumption decreases adrenal responsiveness to adrenocorticotropin (ACTH) stimulation

    International Nuclear Information System (INIS)

    Increased alcohol consumption by adolescents and teenagers has heightened awareness of potential endocrine and developmental alterations. The current study was designed to determine whether chronic ethanol intake alters pituitary and adrenal function in the developing rat. One month old male Sprague Dawley rats were administered 6% ethanol in drinking water. After one month of treatment animals were sacrificed and blood, pituitary and adrenal glands collected. Plasma was assayed for ACTH and corticosterone (CS) by radioimmunossay (RIA). Five anterior pituitary glands per group were challenged with 100 μM corticotropin releasing factor (CRF) for 90 min at 37C under 95% air / 5% CO2. Media were analyzed for either ACTH (pituitary) or CS (adrenal) by RIA. Plasma ACTH and CS were unaffected by ethanol consumption. Pituitary response to CRF was not altered by ethanol. The lack of difference in ACTH release was not due to differences in pituitary content of ACTH. However, chronic ethanol consumption did decrease adrenal responsiveness to ACTH stimulation. In vitro corticosterone production was 1.21 ± 0.14 μg/adrenal in controls and 0.70 ± 0.06 μg/adrenal in ethanol consuming rats

  8. Actions of acute and chronic ethanol on presynaptic terminals.

    Science.gov (United States)

    Roberto, Marisa; Treistman, Steven N; Pietrzykowski, Andrzej Z; Weiner, Jeff; Galindo, Rafael; Mameli, Manuel; Valenzuela, Fernando; Zhu, Ping Jun; Lovinger, David; Zhang, Tao A; Hendricson, Adam H; Morrisett, Richard; Siggins, George Robert

    2006-02-01

    This article presents the proceedings of a symposium entitled "The Tipsy Terminal: Presynaptic Effects of Ethanol" (held at the annual meeting of the Research Society on Alcoholism, in Santa Barbara, CA, June 27, 2005). The objective of this symposium was to focus on a cellular site of ethanol action underrepresented in the alcohol literature, but quickly becoming a "hot" topic. The chairs of the session were Marisa Roberto and George Robert Siggins. Our speakers were chosen on the basis of the diverse electrophysiological and other methods used to discern the effects of acute and chronic ethanol on presynaptic terminals and on the basis of significant insights that their data provide for understanding ethanol actions on neurons in general, as mechanisms underlying problematic behavioral effects of alcohol. The 5 presenters drew from their recent studies examining the effects of acute and chronic ethanol using a range of sophisticated methods from electrophysiological analysis of paired-pulse facilitation and spontaneous and miniature synaptic currents (Drs. Weiner, Valenzuela, Zhu, and Morrisett), to direct recording of ion channel activity and peptide release from acutely isolated synaptic terminals (Dr. Treistman), to direct microscopic observation of vesicular release (Dr. Morrisett). They showed that ethanol administration could both increase and decrease the probability of release of different transmitters from synaptic terminals. The effects of ethanol on synaptic terminals could often be correlated with important behavioral or developmental actions of alcohol. These and other novel findings suggest that future analyses of synaptic effects of ethanol should attempt to ascertain, in multiple brain regions, the role of presynaptic terminals, relevant presynaptic receptors and signal transduction linkages, exocytotic mechanisms, and their involvement in alcohol's behavioral actions. Such studies could lead to new treatment strategies for alcohol intoxication

  9. Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.

    Directory of Open Access Journals (Sweden)

    Maren L Smith

    Full Text Available Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD. Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to 7-days following CIE. Weighted Gene Correlated Network Analysis (WGCNA was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis showed that long-lasting gene regulation occurred 7-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC and hippocampus. Across all brain regions, however, ethanol-responsive expression changes occurred mainly within the first 8-hours after removal from ethanol. Bioinformatics analysis showed that neuroinflammatory responses were seen across multiple brain regions at early time-points, whereas co-expression modules related to neuroplasticity, chromatin remodeling, and neurodevelopment were seen at later time-points and in specific brain regions (PFC or HPC. In PFC a module containing Bdnf was identified as highly CIE responsive in a biphasic manner, with peak changes at 0 hours and 5 days following CIE, suggesting a possible role in mechanisms underlying long-term molecular and behavioral response to CIE. Bioinformatics analysis of this network and several other modules identified Let-7 family microRNAs as potential regulators of gene expression changes induced by CIE. Our results suggest a

  10. Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption.

    Science.gov (United States)

    Smith, Maren L; Lopez, Marcelo F; Archer, Kellie J; Wolen, Aaron R; Becker, Howard C; Miles, Michael F

    2016-01-01

    Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to 7-days following CIE. Weighted Gene Correlated Network Analysis (WGCNA) was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis showed that long-lasting gene regulation occurred 7-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC) and hippocampus. Across all brain regions, however, ethanol-responsive expression changes occurred mainly within the first 8-hours after removal from ethanol. Bioinformatics analysis showed that neuroinflammatory responses were seen across multiple brain regions at early time-points, whereas co-expression modules related to neuroplasticity, chromatin remodeling, and neurodevelopment were seen at later time-points and in specific brain regions (PFC or HPC). In PFC a module containing Bdnf was identified as highly CIE responsive in a biphasic manner, with peak changes at 0 hours and 5 days following CIE, suggesting a possible role in mechanisms underlying long-term molecular and behavioral response to CIE. Bioinformatics analysis of this network and several other modules identified Let-7 family microRNAs as potential regulators of gene expression changes induced by CIE. Our results suggest a complex temporal

  11. Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood.

    Science.gov (United States)

    Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana; Lee, Soon; Markou, Athina

    2016-09-15

    Adolescent ethanol exposure increases risky choice and alters corticotropin releasing factor (CRF) systems in adulthood. The impact of stress on risky choice after adolescent intermittent ethanol (AIE) exposure is not known. We investigated time-specific effects of AIE vapor exposure during early adolescence on risky choice after stress or no stress in adulthood. Male Wistar rats were exposed to air or AIE vapor on postnatal days 28-42 (adolescence) and were exposed to 10days of social defeat or no stress on postnatal days 172-181 (adulthood). Risky choice was assessed in the probability discounting task under baseline conditions and after days 1 and 10 of social defeat. CRF and CRF receptor 1 (CRFR1) mRNA levels were assessed in the prefrontal cortex (PFC) and the central nucleus of the amygdala (CeA) 24h post-stress to evaluate persistent effects of stress on the brain. AIE exposure had no effect on risky choice either at baseline or after social defeat. Additionally, neither acute nor chronic social defeat affected risky choice in air-exposed rats. In the PFC, chronic social defeat selectively decreased CRF mRNA levels in air-exposed rats and increased CRFR1 mRNA levels in all rats. AIE exposure increased CRF mRNA levels in the CeA with no effect of social stress. Our results indicate no effect of ethanol exposure via vapor during early adolescence on risky choice, while our previous findings indicated that AIE exposure via gavage affected risky choice. Both AIE exposure and social defeat altered CRF and CRFR1 mRNA levels in the brain. PMID:27217101

  12. ACUTE PRENATAL EXPOSURE TO ETHANOL AND SOCIAL BEHAVIOR: EFFECT OF AGE, SEX, AND TIMING OF EXPOSURE

    OpenAIRE

    Mooney, Sandra M.; Varlinskaya, Elena I.

    2010-01-01

    During development of the central nervous system, neurons pass through critical periods of vulnerability to environmental factors. Exposure to ethanol during gastrulation or during neuronal generation results in a permanent reduction in the number of neurons in trigeminal-associated cranial nerve nuclei. Normal functioning of the trigeminal system is required for social behavior, the present study examined the effects of acute prenatal exposure to ethanol on social interactions across ontogen...

  13. Ethanol exposure during late gestation and nursing in the rat: effects upon maternal care, ethanol metabolism and infantile milk intake.

    Science.gov (United States)

    Pueta, Mariana; Abate, Paula; Haymal, Olga B; Spear, Norman E; Molina, Juan C

    2008-11-01

    Ethanol experiences, during late gestation as well as during nursing, modify the behavioral dynamics of the dam/pup dyad, and leads to heightened ethanol intake in the offspring. This study focuses on: a) behavioral and metabolic changes in intoxicated dams with previous exposure to ethanol during pregnancy and b) infantile consumption of milk when the dam is either under the effects of ethanol or sober. Pregnant rats received water, 1.0 or 2.0 g/kg ethanol, and were administered with water or ethanol during the postpartum period. Intoxication during nursing disrupted the capability of the dam to retrieve the pups and to adopt a crouching posture. These disruptions were attenuated when dams had exposure to ethanol during pregnancy. Ethanol experiences during gestation did not affect pharmacokinetic processes during nursing, whereas progressive postpartum ethanol experience resulted in metabolic tolerance. Pups suckling from intoxicated dams, with previous ethanol experiences, ingested more milk than did infants suckling from ethanol-intoxicated dams without such experience. Ethanol gestational experience results in subsequent resistance to the drug's disruptions in maternal care. Consequently, better maternal care by an intoxicated dam with ethanol experience during gestation facilitates access of pups to milk which could be contaminated with ethanol. PMID:18602418

  14. Occupational Exposures and Chronic Airflow Limitation

    Directory of Open Access Journals (Sweden)

    Helen Dimich-Ward

    1996-01-01

    Full Text Available The recent literature was reviewed to evaluate whether chronic airflow limitation is associated with occupational exposures to dusts. Only those studies that controlled for the effects of smoking were included. There is compelling evidence that exposure to inorganic dusts, such as from coal and hardrock mining or asbestos, are associated with the development of chronic airflow limitation, independently of pneumoconiosis. Nonsmoking gold miners are particularly at high risk of airflow obstruction and emphysema. Findings from studies of organic dusts, such as exposures to wood, cotton, grain or other agricultural dusts, or to mixed dust exposures, were less consistent but tended to show positive dose-response associations. In the majority of studies, no statistical interaction was shown between dust exposures and smoking; however, the effects of the dust exposures were often more pronounced. An occupational history should be considered, in addition to a smoking history, as an integral part of an investigation of chronic airflow limitation in a patient.

  15. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure

    Science.gov (United States)

    Swartzwelder, H. Scott; Risher, Mary-Louise; Miller, Kelsey M.; Colbran, Roger J.; Winder, Danny G.; Wills, Tiffany A.

    2016-01-01

    Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70) from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further, the robust change in

  16. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

    Directory of Open Access Journals (Sweden)

    H Scott Swartzwelder

    Full Text Available Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70 from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further

  17. The consequence of fetal ethanol exposure and adolescent odor re-exposure on the response to ethanol odor in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    Molina Juan C

    2009-01-01

    Full Text Available Abstract Background An epidemiologic predictive relationship exists between fetal ethanol exposure and the likelihood for adolescent use. Further, an inverse relationship exists between the age of first experience and the probability of adult abuse. Whether and how the combined effects of prenatal and adolescent ethanol experiences contribute to this progressive pattern remains unknown. Fetal ethanol exposure directly changes the odor attributes of ethanol important for both ethanol odor preference behavior and ethanol flavor perception. These effects persist only to adolescence. Here we tested whether adolescent ethanol odor re-exposure: (Experiment 1 augments the fetal effect on the adolescent behavioral response to ethanol odor; and/or (Experiment 2 perpetuates previously observed adolescent behavioral and neurophysiological responses into adulthood. Methods Pregnant rats received either an ethanol or control liquid diet. Progeny (observers experienced ethanol odor in adolescence via social interaction with a peer (demonstrators that received an intragastric infusion of either 1.5 g/kg ethanol or water. Social interactions were scored for the frequency that observers followed their demonstrator. Whole-body plethysmography evaluated the unconditioned behavioral response of observers to ethanol odor in adolescence (P37 or adulthood (P90. The olfactory epithelium of adults was also examined for its neural response to five odorants, including ethanol. Results Experiment 1: Relative to fetal or adolescent exposure alone, adolescent re-exposure enhanced the behavioral response to ethanol odor in P37 animals. Compared to animals with no ethanol experience, rats receiving a single experience (fetal or adolescent show an enhanced, yet equivalent, ethanol odor response. Fetal ethanol experience also increased olfactory-guided following of an intoxicated peer. Experiment 2: Combined exposure yielded persistence of the behavioral effects only in adult

  18. Ethanol exposure during late gestation and nursing in the rat: Effects upon maternal care, ethanol metabolism and infantile milk intake

    OpenAIRE

    Pueta, Mariana; Abate, Paula; Haymal, Olga B.; Norman E. Spear; Molina, Juan C.

    2008-01-01

    Ethanol experiences, during late gestation as well as during nursing, modify the behavioral dynamics of the dam/pup dyad, and leads to heightened ethanol intake in the offspring. This study focuses on: a) behavioral and metabolic changes in intoxicated dams with previous exposure to ethanol during pregnancy and b) infantile consumption of milk when the dam is either under the effects of ethanol or sober. Pregnant rats received water, 1.0 or 2.0 g/kg ethanol, and were administered with water o...

  19. Prenatal Inhalation Exposure to Evaporative Condensates of Gasoline with 15% Ethanol and Evaluation of Sensory Function in Adult Rat Offspring

    Science.gov (United States)

    The introduction of ethanol-blended automotive fuels has raised concerns about potential health effects from inhalation exposure to the combination of ethanol and gasoline hydrocarbon vapors. Previously, we evaluated effects of prenatal inhalation exposure to 100% ethanol (E100) ...

  20. The effect of acute and chronic exposure to ethanol on the developing encephalon: a review Os efeitos da exposição aguda e crônica ao etanol sobre o desenvolvimento do encéfalo: uma revisão

    Directory of Open Access Journals (Sweden)

    Tales Alexandre Aversi-Ferreira

    2008-09-01

    Full Text Available OBJECTIVES: to compare the acute and chronic effects of ethanol on the neural development, by analysis of the ontogenetic neural structure of mammals. METHODS: searches were performed in the following electronic databases: MEDLINE, SciElo, PubMed, LILACS, CAPES periodical, and the Open Journal System. The descriptors used were: "chronic ethanol toxicity", "chronic alcohol toxicity", "acute ethanol toxicity", "acute alcohol", "neural ontogenic development", "neuronal migration disturbances", "neural structure". The following inclusion criteria were used: articles published between 2003 and 2007, some classic articles in the field and an important neuropsychology textbook. RESULTS: the analysis of papers revealed that, although several studies of the chronic effects of ethanol exposure on the mammalian nervous system have been conducted, only a few have investigated the acute effects of ethanol on specific days of gestation, and these studies have revealed important disorders relating to the cerebral tissue. CONCLUSIONS: it should be recommended that women refrain from the consumption of ethanol during gestational phase to protect the fetus' health. Furthermore, the acute consumption of ethanol by women nearing the eighth or ninth week of gestation has been shown to be potentially harmful to the nervous tissue of the fetus.OBJETIVOS: comparar os efeitos agudo e crônico do etanol sobre o desenvolvimento do sistema nervoso através da análise da estrutura ontogênica neural dos mamíferos. MÉTODOS: pesquisas foram feitas nas bases eletrônicas: MEDLINE, SciElo, PubMed, LILACS, CAPES periodical, Open Journal System. Os descritores usados foram: "toxidade crônica ao etanol", "toxidade crônica ao álcool", "toxicidade aguda ao etanol", "toxicidade aguda ao álcool", "desenvolvimento ontogênico neural", "distúrbios da migração neuronal", "estrutura neural".Foram considerados critérios de inclusão: artigos publicados no periódo de 2003 e 2007

  1. Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal

    Institute of Scientific and Technical Information of China (English)

    LIJing; LIYue-Hua; YUANXiao-Ru

    2003-01-01

    AIM: To study the changes in the expression and phosphorylation of cAMP response element binding protein(CREB) in the rat nucleus accumbens after chronic ethanol intake and its withdrawal. METHODS: Ethanol wasgiven in drinking water at the concentration of 6 % (v/v), for one month. Changes in the levels of CREB andphospho-CREB (p-CREB) protein in the nucleus accumbens were measured by immunohistochemistry methods.RESULTS: Ethanol given to rats in drinking water decreased the level of p-CREB protein in the nucleus accumbens(-75 %) at the time of exposure to ethanol. The decrement of p-CREB protein in the nucleus accumbens remainedat 24 h (-35 %) and 72 h (-28 %) of ethanol withdrawal, which recovered toward control level after 7 d of ethanolwithdrawal. However, chronic ethanol, as well as ethanol withdrawal failed to produce any significant alteration inthe level of CREB protein in the nucleus accumbens. Naloxone (alone) treatment of rats had no effect on the levelsof CREB and p-CREB protein in the nucleus accumbens. However, when naloxone was administered concurrentlywith ethanol treatment, it antagonized the down-regulation of p-CREB protein in the nucleus accumbens (142 %) ofrats exposed to ethanol. CONCLUSION: A long-term intake of ethanol solution down-regulates the phosphoryla-tion of CREB in the nucleus accumbens, and those changes can be reversed by naloxone, which may be one kindof the molecular mechanisms associated with ethano1 dependence.

  2. Chronic intermittent ethanol induced axon and myelin degeneration is attenuated by calpain inhibition.

    Science.gov (United States)

    Samantaray, Supriti; Knaryan, Varduhi H; Patel, Kaushal S; Mulholland, Patrick J; Becker, Howard C; Banik, Naren L

    2015-10-01

    Chronic alcohol consumption causes multifaceted damage to the central nervous system (CNS), underlying mechanisms of which are gradually being unraveled. In our previous studies, activation of calpain, a calcium-activated neutral protease has been found to cause detrimental alterations in spinal motor neurons following ethanol (EtOH) exposure in vitro. However, it is not known whether calpain plays a pivotal role in chronic EtOH exposure-induced structural damage to CNS in vivo. To test the possible involvement of calpain in EtOH-associated neurodegenerative mechanisms the present investigation was conducted in a well-established mouse model of alcohol dependence - chronic intermittent EtOH (CIE) exposure and withdrawal. Our studies indicated significant loss of axonal proteins (neurofilament light and heavy, 50-60%), myelin proteins (myelin basic protein, 20-40% proteolipid protein, 25%) and enzyme (2', 3'-cyclic-nucleotide 3'-phosphodiesterase, 21-55%) following CIE in multiple regions of brain including hippocampus, corpus callosum, cerebellum, and importantly in spinal cord. These CIE-induced deleterious effects escalated after withdrawal in each CNS region tested. Increased expression and activity of calpain along with enhanced ratio of active calpain to calpastatin (sole endogenous inhibitor) was observed after withdrawal compared to EtOH exposure. Pharmacological inhibition of calpain with calpeptin (25 μg/kg) prior to each EtOH vapor inhalation significantly attenuated damage to axons and myelin as demonstrated by immuno-profiles of axonal and myelin proteins, and Luxol Fast Blue staining. Calpain inhibition significantly protected the ultrastructural integrity of axons and myelin compared to control as confirmed by electron microscopy. Together, these findings confirm CIE exposure and withdrawal induced structural alterations in axons and myelin, predominantly after withdrawal and corroborate calpain inhibition as a potential protective strategy against

  3. Selective Cognitive Deficits in Adult Rats after Prenatal Exposure to Inhaled Ethanol

    Science.gov (United States)

    Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by i...

  4. Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

    International Nuclear Information System (INIS)

    Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with [3H]inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of [3H]inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggests that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers

  5. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

    International Nuclear Information System (INIS)

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate [14C]glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring [14C]leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, [14C]fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration

  6. SIRT1 IS INVOLVED IN ENERGY METABOLISM: THE ROLE OF CHRONIC ETHANOL FEEDING AND RESVERATROL

    OpenAIRE

    Oliva, Joan; French, Barbara A.; Li, Jun; Bardag-Gorce, Fawzia; Fu, Paul; French, Samuel W.

    2008-01-01

    Sirt1, a deacetylase involved in regulating energy metabolism in response to calorie restriction, is up regulated after chronic ethanol feeding using the intragastric feeding model of alcohol liver disease. PGC1α is also up regulated in response to ethanol. These changes are consistent with activation of the Sirt1/PGC1α pathway of metabolism and aging, involved in alcohol liver disease including steatosis, necrosis and fibrosis of the liver. To test this hypothesis, male rats fed ethanol intr...

  7. Chronic ethanol consumption increases the fragility of rat pancreatic zymogen granules.

    OpenAIRE

    Haber, P S; Wilson, J. S.; Apte, M V; Korsten, M A; Pirola, R. C.

    1994-01-01

    Intracellular activation of pancreatic digestive enzymes by lysosomal hydrolases is thought to be an early event in the pathogenesis of pancreatic injury. As ethanol excess is an important association of pancreatitis, experimental work has been directed towards exploring possible mechanisms whereby ethanol may facilitate contact between inactive digestive enzyme precursors and lysosomal enzymes. The aim of this study was to find out if chronic ethanol administration increases the fragility of...

  8. Enhancement of rat brain metabolism of a tryptophan load by chronic ethanol administration

    OpenAIRE

    1980-01-01

    We have previously shown that chronic ethanol administration enhances brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain secondary to the decreased liver tryptophan pyrrolase activity. We now find that ethanol enhances the brain metabolism of a tryptophan load by the same mechanism. The results are discussed in relation to ethanol preference and the need for further clinical work on the effects of alcoholism on tryptophan metabolism.

  9. Brewing complications: the effect of acute ethanol exposure on wound healing

    OpenAIRE

    Radek, Katherine A.; Ranzer, Matthew J.; DiPietro, Luisa A.

    2009-01-01

    Ethanol consumption is linked to a higher incidence of traumatic wounds and increases the risk for morbidity and mortality following surgical or traumatic injury. One of the most profound effects of acute ethanol exposure on wound healing occurs during the inflammatory response, and altered cytokine production is a primary component. Acute ethanol exposure also impairs the proliferative response during healing, causing delays in epithelial coverage, collagen synthesis, and blood vessel regrow...

  10. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats

    Directory of Open Access Journals (Sweden)

    Jessica Saalfield

    2015-12-01

    Full Text Available Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively would affect ethanol conditioned taste aversions 2 days (CTA1 and >3 weeks (CTA2 post-exposure using supersaccharin and saline as conditioning stimuli (CS, respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25% or water every 48 h from postnatal day (P 25–45 (early AIE or P45-65 (late AIE, or were left non-manipulated (NM. During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.

  11. Adolescent binge-like ethanol exposure reduces basal α-MSH expression in the hypothalamus and the amygdala of adult rats

    Science.gov (United States)

    Lerma-Cabrera, Jose Manuel; Carvajal, Francisca; Alcaraz-Iborra, Manuel; de la Fuente, Leticia; Navarro, Montserrat; Thiele, Todd E.; Cubero, Inmaculada

    2013-01-01

    Melanocortins (MC) are central peptides that have been implicated in the modulation of ethanol consumption. There is experimental evidence that chronic ethanol exposure reduces α-MSH expression in limbic and hypothalamic brain regions and alters central pro-opiomelanocortin (POMC) mRNA activity in adult rats. Adolescence is a critical developmental period of high vulnerability in which ethanol exposure alters corticotropin releasing factor, neuropeptide Y, substance P and neurokinin neuropeptide activities, all of which have key roles in ethanol consumption. Given the involvement of MC and the endogenous inverse agonist AgRP in ethanol drinking, here we evaluate whether a binge-like pattern of ethanol treatment during adolescence has a relevant impact on basal and/or ethanol-stimulated α-MSH and AgRP activities during adulthood. To this end, adolescent Sprague-Dawley rats (beginning at PND25) were pre-treated with either saline (SP group) or binge-like ethanol exposure (BEP group; 3.0 g/kg given in intraperitoneal (i.p.) injections) of one injection per day over two consecutive days, followed by 2 days without injections, repeated for a total of 8 injections. Following 25 ethanol-free days, we evaluated α-MSH and AgRP immunoreactivity (IR) in the limbic and hypothalamic nuclei of adult rats (PND63) in response to ethanol (1.5 or 3.0 g/kg i.p.) and saline. We found that binge-like ethanol exposure during adolescence significantly reduced basal α-MSH IR in the central nucleus of the amygdala (CeA), the arcuate nucleus (Arc) and the paraventricular nucleus of the hypothalamus (PVN) during adulthood. Additionally, acute ethanol elicited AgRP IR in the Arc. Rats given the adolescent ethanol treatment required higher doses of ethanol than saline-treated rats to express AgRP. In light of previous evidence that endogenous MC and AgRP regulate ethanol intake through MC-receptor signaling, we speculate that the α-MSH and AgRP disturbances induced by binge-like ethanol

  12. Chronic Ethanol Intake Modulates Photic and Non-Photic Circadian Phase Responses in the Syrian Hamster

    OpenAIRE

    Seggio, Joseph A.; Logan, Ryan W.; Rosenwasser, Alan M.

    2007-01-01

    Chronic alcohol intake disrupts sleep and other circadian biological rhythms in both human alcoholics and in experimental animals. Recent studies from our laboratory indicate that these effects may be due, in part, to ethanol-induced alterations in fundamental properties of the circadian pacemaker. The present study explored the effects of chronic voluntary ethanol intake (25% v/v) on circadian phase responses to both photic and non-photic stimuli in Syrian hamsters. Hamsters were used in the...

  13. Influence of chronic ethanol consumption on extra-pancreatic secretory function in rat

    Directory of Open Access Journals (Sweden)

    Yoshihisa Urita

    2009-10-01

    Full Text Available Background: The usefulness of the typical direct methods involving duodenal intubation, such as the secretin and secretin–cholecystokinin tests, in the diagnosis of exocrine pancreatic dysfunction is widely accepted. However, these diagnostic tests tend to be avoided because of their technical complexity and the burden on patients. Recently, a simple breath test was developed for assessment of exocrine pancreatic function employing 13C-dipeptide [i.e., benzoyl-L-tyrosyl-[1-13C] alanine (Bz-Tyr-Ala]. Although alcohol abuse causes pancreatic damage in humans, this has been unclear in rats. Aims: The aim of the study is to evaluate the effect of ethanol exposure beginning at an early age on extra-pancreatic secretory function in rats. Materials and Methods: Twelve female rats of the F344 strain aged 12 months were used. Seven rats were fed on a commercial mash food with 16% ethanol solution (Japanese Sake as drinking-fluid since at 29 days of age (ethanol group. The remaining five rats were fed on a nutrient-matched isocaloric diet with water as drinking-fluid (control group. After 24-hr fasting, rats are orally administrated 1cc of water containing sodium 13C-dipeptide (5 mg/kg and housed in an animal chamber. The expired air in the chamber is collected in a breath-sampling bag using a tube and aspiration pump. The 13CO2 concentration is measured using an infrared spectrometer at 10-min interval for 120 min and expressed as delta per mil. Results: The breath 13CO2 level increased and peaked at 20 min in both two groups. In general, 13CO2 excretion peaked rapidly and also decreased sooner in ethanol rats than in control rats. The mean value of the maximal 13CO2 excretion is 34.7 per mil in ethanol rats, greater than in control rats (31.4 per mil, but the difference did not reach the statistically significance. Conclusion: Chronic ethanol feeding beginning at an early age does not affect extra-pancreatic secretory function in rats.

  14. Exposure - dependent effects of ethanol on the innate immune system

    OpenAIRE

    Goral, Joanna; Karavitis, John; Kovacs, Elizabeth J.

    2008-01-01

    Extensive evidence indicates that ethanol (alcohol) has immunomodulatory properties. Many of its effects on innate immune response are dose-dependent, with acute or moderate use associated with attenuated inflammatory responses, and heavy ethanol consumption linked with augmentation of inflammation. Ethanol may modify innate immunity via functional alterations of the cells of the innate immune system. Mounting evidence indicates that ethanol can diversely affect antigen recognition and intrac...

  15. Third trimester-equivalent ethanol exposure causes micro-hemorrhages in the rat brain.

    Science.gov (United States)

    Welch, J H; Mayfield, J J; Leibowitz, A L; Baculis, B C; Valenzuela, C F

    2016-06-01

    Exposure to ethanol during fetal development produces long-lasting neurobehavioral deficits caused by functional alterations in neuronal circuits across multiple brain regions. Therapeutic interventions currently used to treat these deficits are only partially efficacious, which is a consequence of limited understanding of the mechanism of action of ethanol. Here, we describe a novel effect of ethanol in the developing brain. Specifically, we show that exposure of rats to ethanol in vapor chambers during the equivalent to the third trimester of human pregnancy causes brain micro-hemorrhages. This effect was observed both at low and high doses of ethanol vapor exposure, and was not specific to this exposure paradigm as it was also observed when ethanol was administered via intra-esophageal gavage. The vast majority of the micro-hemorrhages were located in the cerebral cortex but were also observed in the hypothalamus, midbrain, olfactory tubercle, and striatum. The auditory, cingulate, insular, motor, orbital, retrosplenial, somatosensory, and visual cortices were primarily affected. Immunohistochemical experiments showed that the micro-hemorrhages caused neuronal loss, as well as reactive astrogliosis and microglial activation. Analysis with the Catwalk test revealed subtle deficits in motor function during adolescence/young adulthood. In conclusion, our study provides additional evidence linking developmental ethanol exposure with alterations in the fetal cerebral vasculature. Given that this effect was observed at moderate levels of ethanol exposure, our findings lend additional support to the recommendation that women abstain from consuming alcoholic beverages during pregnancy. PMID:26964687

  16. An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein

    Science.gov (United States)

    Ahmadi, Abbas; Nikkhoo, Bahram; Mokarizadeh, Aram; Rahmani, Mohammad-Reza; Fakhari, Shohreh; Mohammadi, Mehdi

    2016-01-01

    Introduction Chronic pancreatitis (CP) is an intractable and multi-factorial disorder. Developing appropriate animal models is an essential step in pancreatitis research, and the best ones are those which mimic the human disorder both aetiologically and pathophysiologically. The current study presents an optimised protocol for creating a murine model of CP, which mimics the initial steps of chronic pancreatitis in alcohol chronic pancreatitis and compares it with two other mouse models treated with cerulein or ethanol alone. Material and methods Thirty-two male C57BL/6 mice were randomly selected, divided into four groups, and treated intraperitoneally with saline (10 ml/kg, control group), ethanol (3 g/kg; 30% v/v), cerulein (50 µg/kg), or ethanol + cerulein, for six weeks. Histopathological and immunohistochemical assays for chronic pancreatitis index along with real-time PCR assessments for mRNA levels of inflammatory cytokines and fibrogenic markers were conducted to verify the CP induction. Results The results indicated that CP index (CPI) was significantly increased in ethanol-cerulein mice compared to the saline, ethanol, and cerulein groups (p < 0.001). Interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), α-smooth muscle actin (α-SMA), and myeloperoxidase activity were also significantly greater in both cerulein and ethanol-cerulein groups than in the saline treated animals (p < 0.001). Immunohistochemical analysis revealed enhanced expression of TGF-β and α-SMA in ethanol-cerulein mice compared to the saline group. Conclusions Intraperitoneal (IP) injections of ethanol and cerulein could successfully induce CP in mice. IP injections of ethanol provide higher reproducibility compared to ethanol feeding. The model is simple, non-invasive, reproducible, and time-saving. Since the protocol mimics the initial phases of CP development in alcoholics, it can be used for investigating basic mechanisms and testing

  17. Fas Regulates Macrophage Polarization and Fibrogenic Phenotype in a Model of Chronic Ethanol-Induced Hepatocellular Injury.

    Science.gov (United States)

    Isayama, Fuyumi; Moore, Sherri; Hines, Ian N; Wheeler, Michael D

    2016-06-01

    The role of Fas-mediated apoptosis and its effect on proinflammatory cytokine production in early alcoholic liver disease has not been addressed. Wild-type mice (C57Bl/6) or mice with a functional mutation in the Fas ligand (B6.gld) were given either high-fat control diet or ethanol diet by intragastric cannulation for 2 or 4 weeks. Liver injury, hepatic lipid accumulation, and proinflammatory cytokine production associated with chronic ethanol consumption were largely prevented in B6.gld mice compared with wild-type mice. Conversely, B6.gld mice given ethanol exhibited increases in collagen deposition, hepatic collagen gene expression, and profibrogenic cytokines (eg, transforming growth factor-β and IL-13) and alterations in matrix remodeling proteins (eg, matrix metalloproteinases and tissue inhibitor of metalloproteinases) compared with wild-type mice. Hepatic F4/80(+) macrophage populations were increased significantly in B6.gld mice compared with wild-type mice; hepatic CD3(+) cell populations were not significantly different. Importantly, a shift toward the expression of M2/Th2 cytokines (eg, IL-4 and IL-13) after ethanol exposure was observed in B6.gld mice compared with classical M1 cytokine expression in wild-type mice under similar conditions. In isolated macrophages, stimulation of Fas receptor minimally enhances lipopolysaccharide-induced M1 cytokine production and significantly limits M2 cytokine production. These data support the hypothesis that Fas-mediated signaling is important for an early ethanol-induced proinflammatory response but limits the profibrogenic response, regulating collagen production in response to chronic ethanol. PMID:27102767

  18. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yongke Lu

    2015-10-01

    Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

  19. Altered Anxiety-like Behavior and Long-term Potentiation in the Bed Nucleus of the Stria Terminalis in Adult Mice Exposed to Chronic Social Isolation, Unpredictable Stress and Ethanol Beginning in Adolescence

    OpenAIRE

    Conrad, Kelly L; Winder, Danny G.

    2010-01-01

    Alcohol and chronic stress exposure, especially during adolescence, can lead to an increased risk in adulthood of developing alcohol use disorders (AUDs). To date, however, no study has assessed the potential long-term effects of chronic intermittent and unpredictable ethanol (EtOH) exposure in mice chronically stressed beginning in adolescence on brain function and anxiety-like behaviors in adulthood. In particular, alterations in function of the bed nucleus of the stria terminalis (BNST), a...

  20. Chronic ethanol inhibits receptor-stimulated phosphoinositide hydrolysis in rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales, R.A.; Crews, F.T. (Department of Pharmacology, University of Texas, Austin (USA))

    1991-03-01

    The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of (3H)prazosin and (3H)AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.

  1. Chronic fatigue syndrome following a toxic exposure.

    Science.gov (United States)

    Racciatti, D; Vecchiet, J; Ceccomancini, A; Ricci, F; Pizzigallo, E

    2001-04-10

    Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National Reference Center for CFS Study at the Department of Infectious Diseases of 'G. D'Annunzio' University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression. All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS. PMID:11327394

  2. Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice

    OpenAIRE

    Newton, P. M.; Orr, C J; Wallace, M J; Kim, C.; Shin, H. S.; Messing, R O

    2004-01-01

    N-type calcium channels are modulated by acute and chronic ethanol exposure in vitro at concentrations known to affect humans, but it is not known whether N-type channels are important for behavioral responses to ethanol in vivo. Here, we show that in mice lacking functional N-type calcium channels, voluntary ethanol consumption is reduced and place preference is developed only at a low dose of ethanol. The hypnotic effects of ethanol are also substantially diminished, whereas ethanol-induced...

  3. Prenatal ethanol exposure alters ventricular myocyte contractile function in the offspring of rats: influence of maternal Mg2+ supplementation.

    Science.gov (United States)

    Wold, L E; Norby, F L; Hintz, K K; Colligan, P B; Epstein, P N; Ren, J

    2001-01-01

    Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and impaired ventricular function in a manner similar to postnatal chronic alcohol ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and dietary Mg2+ supplementation was shown to ameliorate ethanol- induced cardiovascular dysfunction such as hypertension. However, the role of gestational Mg2+ supplementation on FAS-related cardiac dysfunction is unknown. This study was conducted to examine the influence of gestational dietary Mg2+ supplementation on prenatal ethanol exposure-induced cardiac contractile response at the ventricular myocyte level. Timed-pregnancy female rats were fed from gestation day 2 with liquid diets containing 0.13 g/L Mg2+ supplemented with ethanol (36%) or additional Mg2+ (0.52 g/L), or both. The pups were maintained on standard rat chow through adulthood, and ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix soft-edge system, and intracellular Ca2+ transients were measured as changes in fura-2 fluorescence intensity (Delta FFI). Offspring from all groups displayed similar growth curves. Myocytes from the ethanol group exhibited reduced cell length, enhanced peak shortening (PS), and shortened time to 90% relengthening (TR90) associated with a normal Delta FFI and time to PS (TPS). Mg2+ reverted the prenatal ethanol-induced alteration in PS and maximal velocity of relengthening. However, it shortened TPS and TR90, and altered the Delta FFI, as well as Ca2+ decay rate by itself. Additionally, myocytes from the ethanol group exhibited impaired responsiveness to increased extracellular Ca2+ or stimulating frequency, which were restored by gestational Mg2+ supplementation. These data suggest that although gestational Mg2+ supplementation may be beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic mothers, caution must be taken, as Mg2

  4. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.

    Science.gov (United States)

    Knapp, Darin J; Harper, Kathryn M; Whitman, Buddy A; Zimomra, Zachary; Breese, George R

    2016-01-01

    Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint) or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE) and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C-C motif) ligand 2 (CCL2), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNFα) and toll-like receptor 4 (TLR4) mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β) while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally-based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1) receptor inhibition in blocking WCE-induced cytokine mRNAs-the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals. Overall, these

  5. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    Science.gov (United States)

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  6. Effects of Ethanol Exposure during Distinct Periods of Brain Development on Hippocampal Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Brian R. Christie

    2013-07-01

    Full Text Available Fetal alcohol spectrum disorders occur when a mother drinks during pregnancy and can greatly influence synaptic plasticity and cognition in the offspring. In this study we determined whether there are periods during brain development that are more susceptible to the effects of ethanol exposure on hippocampal synaptic plasticity. In particular, we evaluated how the ability to elicit long-term potentiation (LTP in the hippocampal dentate gyrus (DG was affected in young adult rats that were exposed to ethanol during either the 1st, 2nd, or 3rd trimester equivalent. As expected, the effects of ethanol on young adult DG LTP were less severe when exposure was limited to a particular trimester equivalent when compared to exposure throughout gestation. In males, ethanol exposure during the 1st, 2nd or 3rd trimester equivalent did not significantly reduce LTP in the DG. In females, ethanol exposure during either the 1st or 2nd trimester equivalents did not impact LTP in early adulthood, but following exposure during the 3rd trimester equivalent alone, LTP was significantly increased in the female DG. These results further exemplify the disparate effects between the ability to elicit LTP in the male and female brain following perinatal ethanol exposure (PNEE.

  7. The time effect of chronic ethanol feeding on phospholipid fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, M.T.; Tang, A.B.; Halsted, C.H.; Phinney, S.D. (Univ. of California, Davis (United States))

    1992-02-26

    The authors have previously shown that chronic ethanol feeding reduces arachidonic acid (AA) and other products of {delta}6 and {delta}5 desaturases in various tissues including muscle, the largest phospholipid (PL) pool. In this study they investigated the time-course effect of ethanol feeding on tissue fatty acid (FA) profiles. Five Yucatan micropigs were fed 89 kcal/kg body wt of diet containing ethanol and fat as 40 and 34% of energy, respectively. Five control pigs were pairfed corn starch instead of ethanol. Corn oil, 61% linoleic acid (LA), supplied most of dietary fat. PL fatty acids were quantitated by thin layer and gas chromatography. Below are FA profiles of control/ethanol groups by wt%. Underlined values differ p<0.05. In liver PL, ethanol resulted in increased LA but decreased palmitic acid, AA and docosahexaenoic acid (DHA) at 2 months. These changes remained constant for 12 months, whereas alpha-linolenic acid and DHA showed a progressive decline. For muscle, however, significant differences were not seen until 12 months. These results indicate time differences in ethanol effect on w6 and w3 FA composition, and that liver and muscle differ in their rates of response to ethanol. Their findings suggest that ethanol affects both desaturase activity and the precursor pool, and thus may alter membrane function.

  8. Ethanol exposure during peripubertal period increases the mast cell number and impairs meiotic and spermatic parameters in adult male rats.

    Science.gov (United States)

    Paula Franco Punhagui, Ana; Rodrigues Vieira, Henrique; Eloisa Munhoz De Lion Siervo, Gláucia; da Rosa, Renata; Scantamburlo Alves Fernandes, Glaura

    2016-06-01

    Puberty is characterized by psychosomatic alterations, whereas chronic ethanol consumption is associated with morphophysiological changes in the male reproductive system. The purpose of this study was to show the toxic effects on testis and epididymal morphophysiology after ethanol administration during peripuberty. To this end, male Wistar rats were divided into two groups: ethanol (E) group: received a 2 g dose of ethanol/kg in 25% (v/v); and control (C) group: received the same volume of filtered water; both were treated by gavage for 54 days. On the 55th day of the experiment, epididymis, and testis were collected for sperm count, histopathology, mast cell count, and morphometry. The vas deferens was collected for sperm motility analysis. The femur and testicle were used for cytogenetic analysis. Ethanol exposure caused reduction in daily sperm production (DSP) and in sperm motility, multinucleated cells or those having no chromosomal content, and late chromosome migrations. No changes were observed in the number of chromosomes in the mitotic analysis. However, some alterations could be seen in meiocytes at different stages of cell division. Stereological analysis of the epididymis indicated reorganization of its component in the 2A and 5A/B regions. The epididymal cauda had greater recruitment, and both degranulated and full mast cells showed an increase in the initial segment, in the ethanol group. In conclusion, ethanol administration during the pubertal phase affects epididymis and testis in adult rats, as indicated mainly by our new findings related to mast cell number and meiotic impact. Microsc. Res. Tech. 79:541-549, 2016. © 2016 Wiley Periodicals, Inc. PMID:27058992

  9. Early embryonic ethanol exposure impairs shoaling and the dopaminergic and serotoninergic systems in adult zebrafish

    OpenAIRE

    Buske, Christine; Gerlai, Robert

    2011-01-01

    Fetal Alcohol Syndrome (FAS) is a devastating disorder accompanied by numerous morphological and behavioral abnormalities. Human FAS has been modeled in laboratory animals including the zebrafish. Recently, embryonic exposure to low doses of ethanol has been shown to impair behavior without any gross morphological alterations in zebrafish. The exposed zebrafish showed reduced responses to animated conspecific images. The effect of embryonic ethanol exposure, however, has not been investigated...

  10. Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

    Science.gov (United States)

    Udoh, Uduak S.; Swain, Telisha M.; Filiano, Ashley N.; Gamble, Karen L.; Young, Martin E.

    2015-01-01

    Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease. PMID:25857999

  11. Camellia sinensis (L.) Kuntze Extract Ameliorates Chronic Ethanol-Induced Hepatotoxicity in Albino Rats

    OpenAIRE

    Poonam Lodhi; Neeraj Tandan; Neera Singh; Divyansh Kumar; Monu Kumar

    2014-01-01

    The goal of this study was to investigate the hepatoprotective effects of aqueous extract of Camellia sinensis or green tea extract (AQGTE) in chronic ethanol-induced albino rats. All animals were divided into 4 groups in the study for a 5-week duration. 50% ethanol was given orally to the rats with two doses (5 mg/kg bw and 10 mg/kg bw) of AQGTE. Ethanol administration caused a significant increase in the levels of plasma and serum enzymatic markers, alanine aminotransferase (ALT), aspartate...

  12. Operant Ethanol Self-Administration in Ethanol Dependent Mice

    OpenAIRE

    Lopez, Marcelo F; Howard C Becker

    2014-01-01

    While rats have been predominantly used to study operant ethanol self-administration behavior in the context of dependence, several studies have employed operant conditioning procedures to examine changes in ethanol self-administration behavior as a function of chronic ethanol exposure and withdrawal experience in mice. This review highlights some of the advantages of using operant conditioning procedures for examining the motivational effects of ethanol in animals with a history of dependenc...

  13. Preference for ethanol in zebrafish following a single exposure

    OpenAIRE

    Mathur, Priya; Berberoglu, Michael; Guo, Su

    2010-01-01

    Ethanol is one of the most widely abused drugs in the world. Its addictive property is believed to primarily stem from its ability to influence the brain reinforcement pathway evolved for mediating natural rewards. Although dopamine is a known component of the reinforcement pathway, clear molecular and cellular compositions of this pathway and its sensitivity to ethanol remain not well understood. Zebrafish has been increasingly used to model and understand human disease states, due to its ge...

  14. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  15. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    International Nuclear Information System (INIS)

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  16. Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects

    Directory of Open Access Journals (Sweden)

    Swapnalee Sarmah

    2013-08-01

    Fetal alcohol spectrum disorder (FASD occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell, prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented that characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression was not affected by ethanol exposure, but E-cadherin distribution, which controls epiboly and gastrulation, was changed. E-cadherin was redistributed into cytoplasmic aggregates in blastomeres and dramatically redistributed in the extraembryonic yolk cell. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a, which controls epiboly, was significantly reduced in ethanol exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.

  17. Intermittent exposure to ethanol vapor affects osteoblast behaviour more severely than estrogen deficiency does

    International Nuclear Information System (INIS)

    With rising rates of alcohol consumption acute and chronic damage from alcohol is expected to increase all over the world. Habitual excessive alcohol consumption is associated with pathological effects on bone. The aim of the present in vitro study was to investigate comparatively the proliferation and synthetic activity of osteoblasts (OB) isolated from the trabecular bone of rats previously exposed to 7-week intermittent exposure to ethanol vapor, sham-aged rats and long-term estrogen deficient rats. Cell proliferation (WST1) and synthesis of alkaline phosphatase (ALP), osteocalcin (OC), collagen I (CICP), transforming growth factor beta1 (TGF-β1), interleukin-6 (IL-6), tumor necrosis factor alfa (TNFα) were measured at 3, 7 and 14 days of culture. Osteoblast proliferation rate and TGF-β1, IL-6 and TNFα syntheses were significantly affected by alcohol exposure. Estrogen deficiency and alcohol consumption share many common pathophysiological mechanisms of damage to bone, but alcohol affects OB proliferation and TNFα synthesis significantly more than menopause does. Therefore, these in vitro data suggest that alcohol has even more deleterious effects on bone than estrogen deficiency does

  18. The effects of chronic ethanol self-administration on hippocampal serotonin transporter density in monkeys

    Directory of Open Access Journals (Sweden)

    Elizabeth J Burnett

    2012-04-01

    Full Text Available Evidence for an interaction between alcohol consumption and the serotonin system has been observed repeatedly in both humans and animal models yet the specific relationship between the two remains unclear. Research has focused primarily on the serotonin transporter (SERT due in part to its role in regulating extracellular levels of serotonin. The hippocampal formation is heavily innervated by ascending serotonin fibers and is a major component of the neurocircuitry involved in mediating the reinforcing effects of alcohol. The current study investigated the effects of chronic ethanol self-administration on hippocampal SERT in a layer and field specific manner using a monkey model of human alcohol consumption. [3H]Citalopram was used to measure hippocampal SERT density in male cynomolgus macaques that voluntarily self-administered ethanol for 18 months. Hippocampal [3H]citalopram binding was less dense in ethanol drinkers than in controls, with the greatest effect observed in the molecular layer of the dentate gyrus. SERT density was not correlated with measures of ethanol consumption or blood ethanol concentrations, suggesting the possibility that a threshold level of consumption had been met. The lower hippocampal SERT density observed suggests that chronic ethanol consumption is associated with altered serotonergic modulation of hippocampal neurotransmission.

  19. Chronic ethanol intake leads to structural and molecular alterations in the rat endometrium.

    Science.gov (United States)

    Martinez, Marcelo; Milton, Flora A; Pinheiro, Patricia Fernanda F; Almeida-Francia, Camila C D; Cagnon-Quitete, Valeria H A; Tirapelli, Luiz F; Padovani, Carlos Roberto; Chuffa, Luiz Gustavo A; Martinez, Francisco Eduardo

    2016-05-01

    We described the effects of low- and high-dose ethanol intake on the structure and apoptosis signaling of the uterine endometrium of UChA and UChB rats (animals with voluntary ethanol consumption). Thirty adult female rats, 90 days old, were divided into three groups (n = 10/group): UChA rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking water or ethanol) drinking from 2 to 5 g/kg/day; control rats without ethanol (only water). After 120 days of treatment, rats displaying estrus were euthanized. Uterine epithelial cells of the UCh rats showed dilated cisterns of the rough endoplasmic reticulum, presence of lipid droplets, altered nuclear chromatin, and disrupted mitochondria. The UCh rats exhibited intense atrophied epithelial cells with smaller areas and perimeters of cytoplasm and nuclei. The endometrium of UChA rats showed higher levels of caspase-3 while Xiap and Bcl2 varied from moderate to weak. Both UChA and UChB rats exhibited a stronger immunoreaction to Ki-67 and IGFR-1 on epithelial and stromal cells. Chronic ethanol intake leads to structural and molecular alterations in the uterine endometrium of UCh rats, regardless of low- or high-dose consumption, promoting reproductive disorders. PMID:27139238

  20. Lipidomic changes in rat liver after long-term exposure to ethanol

    International Nuclear Information System (INIS)

    Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD. - Highlights: → Long term exposure to ethanol was studied. → A nuclear magnetic resonance (NMR) spectroscopy based lipidomic approach was used. → We examined the clustering pattern of the NMR data with principal component analysis. → NMR data were compared with histology and

  1. Depression of biliary glutathione excretion by chronic ethanol feeding in the rat

    International Nuclear Information System (INIS)

    The effects of chronic alcohol feeding on biliary glutathione excretion were studied in rats pair fed diets containing either ethanol (36% of total energy) or isocaloric carbohydrate for 4-6 weeks. An exteriorized biliary-duodenal fistula was established and total glutathione (GSH) and oxidized glutathione (GSSG) were measured. A significant decrease was observed in rats fed alcohol chronically compared to their pair fed controls in the biliary excretion of GSH (55.7 +/- 37.0 vs 243.1 +/- 29.0 μg/ml bile, p 35-L-methionine incorporation into hepatic and biliary GSH was unchanged or even increased after chronic ethanol feeding. 22 references, 4 figures

  2. Ethanol in low chronic dose level attenuates major organic effects in malnourished rats

    OpenAIRE

    ALINE S DE AGUIAR; GILSON T BOAVENTURA; RAFAEL F ABRAHÃO; THATIANA L FREITAS; Takiya, Christina M; PORPHIRIO J S FILHO; VILMA A DA SILVA

    2009-01-01

    The aim of the present study was to evaluate the chronic toxicity of ethanol low blood levels in malnourished rats. Female Wistar rats (220 g) were subjected to either an ad libitum diet (W, well-nourished, n=10) or food restriction (M, malnourished, n=10). Water (WW and MW) or ethanol solution (W5% and M5%) was offered to half of each nutritional group (n=5) as the only fluid source. The treatment was continued for two months. After sacrifice, blood biochemical parameters and macroscopic, hi...

  3. Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

    Science.gov (United States)

    Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M

    2011-11-20

    Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. PMID:21767576

  4. Consequences of adolescent ethanol exposure in male Sprague-Dawley rats on fear conditioning and extinction in adulthood

    Science.gov (United States)

    Broadwater, Margaret A.

    Some evidence suggests that adolescents are more vulnerable than adults to alcohol-induced cognitive deficits and that these deficits may persist into adulthood. Five experiments were conducted to assess long-term consequences of ethanol exposure on tone and context Pavlovian fear conditioning in male Sprague-Dawley rats. Experiment 1 examined age-related differences in sensitivity to ethanol-induced disruptions of fear conditioning to a pre-conditioning ethanol challenge. Experiments 2 examined fear conditioning 22 days after early-mid adolescent (P28-48) or adult (P70-90) exposure to 4 g/kg i.g. ethanol or water given every other day (total of 11 exposures). In Experiment 3, mid-late adolescents (P35-55) were exposed in the same manner to assess whether timing of ethanol exposure within the adolescent period would differentially affect later fear conditioning. Experiment 4 assessed the influence of prior adolescent or adult ethanol exposure on the disrupting effects of a pre-conditioning ethanol challenge. In Experiment 5, neurogenesis (doublecortin---DCX) and cholinergic (choline acetyltransferase---ChAT) markers were measured to assess potential long-term ethanol-induced changes in neural mechanisms important for learning and memory. Results indicated that the long-lasting behavioral effects of ethanol exposure varied depending on exposure age, with early-mid adolescent exposed animals showing attenuated context fear retention (a relatively hippocampal-dependent task), whereas mid-late adolescent and adult exposed animals showed slower context extinction (thought to be reliant on the mPFC). Early-mid adolescent ethanol-exposed animals also had significantly less DCX and ChAT expression than their water-exposed counterparts, possibly contributing to deficits in context fear. Tone fear was not influenced by prior ethanol exposure at any age. In terms of age differences in ethanol sensitivity, adolescents were less sensitive than adults to ethanol

  5. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    Science.gov (United States)

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. PMID:25940002

  6. Effects of embryonic ethanol exposure at low doses on neuronal development, voluntary ethanol consumption and related behaviors in larval and adult zebrafish: Role of hypothalamic orexigenic peptides.

    Science.gov (United States)

    Sterling, M E; Chang, G-Q; Karatayev, O; Chang, S Y; Leibowitz, S F

    2016-05-01

    Embryonic exposure to ethanol is known to affect neurochemical systems in rodents and increase alcohol drinking and related behaviors in humans and rodents. With zebrafish emerging as a powerful tool for uncovering neural mechanisms of numerous diseases and exhibiting similarities to rodents, the present report building on our rat studies examined in zebrafish the effects of embryonic ethanol exposure on hypothalamic neurogenesis, expression of orexigenic neuropeptides, and voluntary ethanol consumption and locomotor behaviors in larval and adult zebrafish, and also effects of central neuropeptide injections on these behaviors affected by ethanol. At 24h post-fertilization, zebrafish embryos were exposed for 2h to ethanol, at low concentrations of 0.25% and 0.5%, in the tank water. Embryonic ethanol compared to control dose-dependently increased hypothalamic neurogenesis and the proliferation and expression of the orexigenic peptides, galanin (GAL) and orexin (OX), in the anterior hypothalamus. These changes in hypothalamic peptide neurons were accompanied by an increase in voluntary consumption of 10% ethanol-gelatin and in novelty-induced locomotor and exploratory behavior in adult zebrafish and locomotor activity in larvae. After intracerebroventricular injection, these peptides compared to vehicle had specific effects on these behaviors altered by ethanol, with GAL stimulating consumption of 10% ethanol-gelatin more than plain gelatin food and OX stimulating novelty-induced locomotor behavior while increasing intake of food and ethanol equally. These results, similar to those obtained in rats, suggest that the ethanol-induced increase in genesis and expression of these hypothalamic peptide neurons contribute to the behavioral changes induced by embryonic exposure to ethanol. PMID:26778786

  7. Exposures due to emissions from ethanol and diesel fuelled buses in Stockholm

    Energy Technology Data Exchange (ETDEWEB)

    Otson, R. [Health Canada, Ottawa, ON (Canada); Westerholm, R. [Stockholm Univ. (Sweden). Dept. of Analytical Chemistry; Fellin, P.; Davis, C. [BOVAR Environmental, Toronto, ON (Canada)

    1997-12-01

    Personal exposure and ambient concentrations of 105 chemical species were determined during September in Stockholm, a northern urban area. This unique study provided personal exposure data equivalent to 8 person-days each on diesel and ethanol buses, and 12 person-days on streets in the urban area. If used judiciously, these data, and the ambient data, are useful for risk assessment, as well as for validation of dispersion models. The concentrations for many species were relatively low, when compared to results from other studies of outdoor concentrations in urban areas. This was probably due to the meteorological conditions during the study which favoured low concentrations. Personal exposures were generally higher than ambient concentrations, probably because of the proximity of subjects to sources of contaminants. As expected, alcohol compounds were found at greater levels in ethanol fueled buses and at bus stops on routes with predominantly ethanol fueled buses. No trends were evident for exposures of VOCs or PAC on diesel and ethanol buses. Exposures to particles at the bus stops were lower than exposures on buses, possibly due to the low traffic volumes at the bus stops, and the proximity of subjects on buses to other traffic. Upon factor analysis of the data, five factors explained the majority of the variance in the results, and showed associations between selected species and a few other parameters. These associations should be useful to design more efficient studies in the future. The chemical element mass balance results with measured profiles yielded uncertain results, but with literature profiles, the diesel and ethanol bus emissions accounted for a small fraction, i.e. < 5%, of the exposures 26 refs, 6 figs, 3 tabs

  8. Transcriptome Profiling Reveals Disruption of Innate Immunity in Chronic Heavy Ethanol Consuming Female Rhesus Macaques

    Science.gov (United States)

    Sureshchandra, Suhas; Rais, Maham; Stull, Cara; Grant, Kathleen; Messaoudi, Ilhem

    2016-01-01

    It is well established that heavy ethanol consumption interferes with the immune system and inflammatory processes, resulting in increased risk for infectious and chronic diseases. However, these processes have yet to be systematically studied in a dose and sex-dependent manner. In this study, we investigated the impact of chronic heavy ethanol consumption on gene expression using RNA-seq in peripheral blood mononuclear cells isolated from female rhesus macaques with daily consumption of 4% ethanol available 22hr/day for 12 months resulting in average ethanol consumption of 4.3 g/kg/day (considered heavy drinking). Differential gene expression analysis was performed using edgeR and gene enrichment analysis using MetaCore™. We identified 1106 differentially expressed genes, meeting the criterion of ≥ two-fold change and p-value ≤ 0.05 in expression (445 up- and 661 down-regulated). Pathway analysis of the 879 genes with characterized identifiers showed that the most enriched gene ontology processes were “response to wounding”, “blood coagulation”, “immune system process”, and “regulation of signaling”. Changes in gene expression were seen despite the lack of differences in the frequency of any major immune cell subtype between ethanol and controls, suggesting that heavy ethanol consumption modulates gene expression at the cellular level rather than altering the distribution of peripheral blood mononuclear cells. Collectively, these observations provide mechanisms to explain the higher incidence of infection, delay in wound healing, and increase in cardiovascular disease seen in subjects with Alcohol use disorder. PMID:27427759

  9. Betaine (trimethylglycine) as a nutritional agent prevents oxidative stress after chronic ethanol consumption in pancreatic tissue of rats.

    Science.gov (United States)

    Kanbak, Gungör; Dokumacioglu, Ali; Tektas, Aysegul; Kartkaya, Kazim; Erden Inal, Mine

    2009-03-01

    In this study, we investigated the free radical-mediated cytotoxic effects of chronic ethanol consumption on the pancreatic tissue and a possible cytoprotective effect of betaine as a methyl donor and an important participant in the methionine cycle. Twenty-four male Wistar rats were divided into control, ethanol, and ethanol+betaine groups. Prior to sacrifice, all groups were fed 60 mL/diet per day for two months. Rats in the ethanol group were fed with ethanol 8 g/kg/day. The ethanol+betaine groups were fed ethanol plus betaine (0.5 % w/v). Malondialdehyde levels and adenosine deaminase, superoxide dismutase, and xanthine oxidase activities were determined in pancreatic tissues of rats. Compared to control group, MDA levels increased significantly in the ethanol group (p<0.05). MDA levels in the ethanol+betaine group were significantly decreased compared to the ethanol group (p<0.05). ADA activity in the ethanol+betaine group decreased significantly when compared to the ethanol group (p<0.05). XO activities in ethanol-fed rats were decreased significantly compared to the control group (p<0.05). XO activity in the betaine group was increased significantly (p<0.05) compared to the ethanol group. SOD activity in the ethanol group decreased significantly compared to control group (p<0.001). SOD activity in the ethanol+betaine group decreased significantly (p<0.05) compared to the control group. We think that betaine, as a nutritional methylating agent, may be effective against ethanol-mediated oxidative stress in pancreatic tissue. PMID:20108209

  10. Sensitivity of Trout to Chronic Acute Exposure to Selenium

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel; Nielsen, M. Gissel

    1978-01-01

    Trout were exposed to selenite (Na2SeO3) solutions of varying concentrations (0.1-100 ppm Se) for periods of up to 4 wk. A chronic exposure to 0.1 ppm Se or less is non-lethal to trout. Lethality at higher concentrations depends on the length of exposure. Trout that survive for 10 days in tap...

  11. Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice

    International Nuclear Information System (INIS)

    Chronic consumption of ethanol can cause cumulative liver damage that can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis, we investigated the global intrahepatic gene expression profiles of livers from mice administered alcohol. Ethanol was administered by feeding the standard Lieber-DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples revealed fatty changes and punctate necrosis in the high-dose group and ballooning degeneration in the low-dose group. In total, 292 genes were identified as ethanol responsive, and several of these differed significantly in expression compared to those of control mice (two-way ANOVA; p < 0.05). Specifically, the expression levels of genes involved in hepatic lipid transport and metabolism were examined. An overall net increase in gene expression was observed for genes involved in (i) glucose transport and glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid esterification to triglycerides, and (iv) cholesterol transport, de novo cholesterol synthesis, and bile acid synthesis. Collectively, these data provide useful information concerning the global gene expression changes that occur due to alcohol intake and provide important insights into the comprehensive mechanisms of chronic alcoholic steatosis

  12. Embryonic Ethanol Exposure Dysregulates BMP and Notch Signaling, Leading to Persistent Atrio-Ventricular Valve Defects in Zebrafish.

    Science.gov (United States)

    Sarmah, Swapnalee; Muralidharan, Pooja; Marrs, James A

    2016-01-01

    Fetal alcohol spectrum disorder (FASD), birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs), the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3-24 hours post fertilization) led to defects in atrio-ventricular (AV) valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC). Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/β-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish. PMID:27556898

  13. Chronic ethanol attenuates circadian photic phase resetting and alters nocturnal activity patterns in the hamster

    OpenAIRE

    Ruby, Christina L.; Brager, Allison J.; Marc A. DePaul; Prosser, Rebecca A.; Glass, J. David

    2009-01-01

    Acute ethanol (EtOH) administration impairs circadian clock phase resetting, suggesting a mode for the disruptive effect of alcohol abuse on human circadian rhythms. Here, we extend this research by characterizing the chronobiological effects of chronic alcohol consumption. First, daily profiles of EtOH were measured in the suprachiasmatic nucleus (SCN) and subcutaneously using microdialysis in hamsters drinking EtOH. In both cases, EtOH peaked near lights-off and declined throughout the dark...

  14. Ethanol regulation of adenosine receptor-stimulated cAMP levels in a clonal neural cell line: an in vitro model of cellular tolerance to ethanol.

    OpenAIRE

    Gordon, A S; Collier, K; Diamond, I.

    1986-01-01

    The acute and chronic neurologic effects of ethanol appear to be due to its interaction with neural cell membranes. Chronic exposure to ethanol induces changes in the membrane that lead to tolerance to the effects of ethanol. However, the actual membrane changes that account for tolerance to ethanol are not understood. We have developed a model cell culture system, using NG108-15 neuroblastoma-glioma hybrid cells, to study cellular tolerance to ethanol. We have found that adenosine receptor-s...

  15. TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS

    Science.gov (United States)

    Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukary...

  16. Chronic ethanol administration increases the binding of 3H Ro-15-4513 in primary cultured spinal cord neurons

    International Nuclear Information System (INIS)

    Ro 15-4513 (ethyl-8-azido-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5α], [1,4] benzodiazepine-3-carboxylate) is reported to be a selective ethanol antagonist in biochemical and behavioral studies. The effect of chronic ethanol treatment on the binding of [3H]Ro 15-4513 was investigated in cultured spinal cord neurons, which are shown to possess all the elements of GABA benzodiazepine receptor complex. Chronic ethanol treatment (50 mM for 6 hr, 12 hr, 18 hr, 3 days, and 53 days) produced an increase in the specific binding of [3H]Ro 15-4513. The increase in binding in these neurons was due to an increase in the number (Bmax) of receptor sites. This effect was specific for Ro 15-4513, since identical ethanol treatment did not alter the binding of benzodiazepine antagonist [3H]Ro 15-1788 or agonist [3H]flunitrazepam or inverse agonist [3H]methyl-β-carboline-3-carboxylate. Similar results have been reported following chronic ethanol treatment to rats. These results suggest that the Ro 15-4513 binding sites on the oligomeric GABA receptor complex are altered following chronic ethanol administration, and support the notion of a unique role of Ro 15-4513 as an ethanol antagonist

  17. Prenatal exposure to ethanol stimulates hypothalamic CCR2 chemokine receptor system: Possible relation to increased density of orexigenic peptide neurons and ethanol drinking in adolescent offspring.

    Science.gov (United States)

    Chang, G-Q; Karatayev, O; Leibowitz, S F

    2015-12-01

    Clinical and animal studies indicate that maternal consumption of ethanol during pregnancy increases alcohol drinking in the offspring. Possible underlying mechanisms may involve orexigenic peptides, which are stimulated by prenatal ethanol exposure and themselves promote drinking. Building on evidence that ethanol stimulates neuroimmune factors such as the chemokine CCL2 that in adult rats is shown to colocalize with the orexigenic peptide, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), the present study sought to investigate the possibility that CCL2 or its receptor CCR2 in LH is stimulated by prenatal ethanol exposure, perhaps specifically within MCH neurons. Our paradigm of intraoral administration of ethanol to pregnant rats, at low-to-moderate doses (1 or 3g/kg/day) during peak hypothalamic neurogenesis, caused in adolescent male offspring twofold increase in drinking of and preference for ethanol and reinstatement of ethanol drinking in a two-bottle choice paradigm under an intermittent access schedule. This effect of prenatal ethanol exposure was associated with an increased expression of MCH and density of MCH(+) neurons in LH of preadolescent offspring. Whereas CCL2(+) cells at this age were low in density and unaffected by ethanol, CCR2(+) cells were dense in LH and increased by prenatal ethanol, with a large percentage (83-87%) identified as neurons and found to colocalize MCH. Prenatal ethanol also stimulated the genesis of CCR2(+) and MCH(+) neurons in the embryo, which co-labeled the proliferation marker, BrdU. Ethanol also increased the genesis and density of neurons that co-expressed CCR2 and MCH in LH, with triple-labeled CCR2(+)/MCH(+)/BrdU(+) neurons that were absent in control rats accounting for 35% of newly generated neurons in ethanol-exposed rats. With both the chemokine and MCH systems believed to promote ethanol consumption, this greater density of CCR2(+)/MCH(+) neurons in the LH of preadolescent rats suggests that

  18. Rutin ameliorates glycemic index, lipid profile and enzymatic activities in serum, heart and liver tissues of rats fed with a combination of hypercaloric diet and chronic ethanol consumption.

    Science.gov (United States)

    Chuffa, Luiz Gustavo A; Fioruci-Fontanelli, Beatriz A; Bordon, Juliana G; Pires, Rafaelle B; Braga, Camila P; Seiva, Fábio R F; Fernandes, Ana Angélica H

    2014-06-01

    Alcoholism and obesity are strongly associated with several disorders including heart and liver diseases. This study evaluated the effects of rutin treatment in serum, heart and liver tissues of rats subjected to a combination of hypercaloric diet (HD) and chronic ethanol consumption. Rats were divided into three groups: Control: rats fed a standard diet and drinking water ad libitum; G1: rats fed the HD and receiving a solution of 10% (v/v) ethanol; and G2: rats fed the HD and ethanol solution, followed by injections of 50 mg/kg(-1) rutin as treatment. After 53 days of HD and ethanol exposure, the rutin was administered every three days for nine days. At the end of the experimental period (95 days), biochemical analyses were carried out on sera, cardiac and hepatic tissues. Body weight gain and food consumption were reduced in both the G1 and G2 groups compared to control animals. Rutin effectively reduced the total lipids (TL), triglycerides (TG), total cholesterol (TC), VLDL, LDL-cholesterol and glucose levels, while it increased the HDL-cholesterol in the serum of G2 rats, compared to G1. Although rutin had no effect on total protein, albumin, uric acid and cretinine levels, it was able to restore serum activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) in animals fed HD and receiving ethanol. Glycogen stores were replenished in both hepatic and cardiac tissues after rutin treatment. Moreover, rutin consistently reduced hepatic levels of TG and TC and cardiac AST, ALT and CK activities. Thus, rutin treatment was effective in reducing the risk factors for cardiac and hepatic disease caused by both HD and chronic ethanol consumption. PMID:25204084

  19. The effects of prepubertal gonadectomy and binge-like ethanol exposure during adolescence on ethanol drinking in adult male and female rats

    Science.gov (United States)

    Sherrill, Luke K.; Koss, Wendy A.; Foreman, Emily S.; Gulley, Joshua M.

    2010-01-01

    The pubertal surge in gonadal hormones that occurs during adolescence may impact the long-term effects of early alcohol exposure and sex differences in drinking behavior in adulthood. We investigated this hypothesis by performing sham or gonadectomy surgeries in Long Evans rats around postnatal day (P) 20. From P35–45, males and females were given saline or 3.0 g/kg ethanol using a binge-like model of exposure (8 injections total). As adults (P100), they were trained to self-administer ethanol via a sucrose-fading procedure and then given access to different unsweetened concentrations (5–20% w/v) for 5 days/concentration. We found that during adolescence, ethanol-induced intoxication was similar in males and females that underwent sham surgery. In gonadectomized males and females, however, the level of intoxication was greater following the last injection compared to the first. During adulthood, females drank more sucrose per body weight than males and binge-like exposure to ethanol reduced sucrose consumption in both sexes. These effects were not seen in gonadectomized rats. Ethanol consumption was higher in saline-exposed females compared to males, with gonadectomy reversing this sex difference by increasing consumption in males and decreasing it in females. Exposure to ethanol during adolescence augmented ethanol consumption in both sexes, but this effect was statistically significant only in gonadectomized females. Together, these results support a role for gonadal hormones during puberty in the short- and long-term effects of ethanol on behavior and in the development of sex differences in consummatory behavior during adulthood. PMID:20816899

  20. Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats

    OpenAIRE

    Sherrill, Luke K.; Berthold, Claire; Koss, Wendy A.; Juraska, Janice M.; Gulley, Joshua M.

    2011-01-01

    Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol s aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and f...

  1. The effects of pre-pubertal gonadectomy and binge-like ethanol exposure during adolescence on ethanol drinking in adult male and female rats.

    Science.gov (United States)

    Sherrill, Luke K; Koss, Wendy A; Foreman, Emily S; Gulley, Joshua M

    2011-01-20

    The pubertal surge in gonadal hormones that occurs during adolescence may impact the long-term effects of early alcohol exposure and sex differences in drinking behavior in adulthood. We investigated this hypothesis by performing sham or gonadectomy surgeries in Long-Evans rats around post-natal day (P) 20. From P35-45, males and females were given saline or 3.0 g/kg ethanol using a binge-like model of exposure (8 injections total). As adults (P100), they were trained to self-administer ethanol via a sucrose-fading procedure and then given access to different unsweetened concentrations (5-20%, w/v) for 5 days/concentration. We found that during adolescence, ethanol-induced intoxication was similar in males and females that underwent sham surgery. In gonadectomized males and females, however, the level of intoxication was greater following the last injection compared to the first. During adulthood, females drank more sucrose per body weight than males and binge-like exposure to ethanol reduced sucrose consumption in both sexes. These effects were not seen in gonadectomized rats. Ethanol consumption was higher in saline-exposed females compared to males, with gonadectomy reversing this sex difference by increasing consumption in males and decreasing it in females. Exposure to ethanol during adolescence augmented ethanol consumption in both sexes, but this effect was statistically significant only in gonadectomized females. Together, these results support a role for gonadal hormones during puberty in the short- and long-term effects of ethanol on behavior and in the development of sex differences in consummatory behavior during adulthood. PMID:20816899

  2. Impact of chronic and acute pesticide exposures on periphyton communities

    International Nuclear Information System (INIS)

    Aquatic ecosystems face variable exposure to pesticides, especially during floodings which are associated with short bursts of high contaminant concentrations that influence biological systems. A study was undertaken to highlight the impact of the herbicide diuron applied in mixture with the fungicide tebuconazole on natural periphyton during flooding events. Periphyton were grown in two series of two lotic outdoor mesocosms: one series was non-contaminated while the other was exposed to chronic contamination. After 4 weeks, one channel of each series was exposed to three successive pulses, with each pulse followed by one week of recovery. Impacts on periphyton were assessed by using Denaturing Gel Gradient Electrophoresis to characterize eukaryotic community structure. At a functional scale, photosynthetic efficiency was quantified during each pulse, and the induced tolerance to diuron was estimated by performing short-term inhibition tests based on photosynthetic efficiency. Moreover, pesticide concentrations in the water column and periphyton matrix were measured. Diuron was adsorbed in the periphyton during each pulse and desorbed 13 h after pulse end. The different pulses affected the eukaryotic community structures of the control biofilms, but not of the chronically exposed ones. During the first pulse, photosynthetic efficiency was correlated with pesticide concentration in the water phase, and there was no difference between periphyton from chronically contaminated channels and control channels. However, during the second and third pulses, the photosynthetic efficiency of periphyton chronically exposed to pesticides appeared to be less impacted by the acute pulsed exposure of pesticide. These changes were consistent with the acquisition of induced tolerance to diuron since only after the third pulse that periphyton from chronic channel became tolerant to diuron. Our experimental study indicates that the effects of pulsed acute exposures to pesticides on

  3. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    Energy Technology Data Exchange (ETDEWEB)

    Leu, Yu-Wei [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Chu, Pei-Yi [Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan (China); Chen, Chien-Min [Division of Neurosurgery, Changhua Christian Hospital, Changhua 500, Taiwan (China); Yeh, Kun-Tu [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China); Hsiao, Shu-Huei, E-mail: bioshh@ccu.edu.tw [Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan (China)

    2014-10-24

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.

  4. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    International Nuclear Information System (INIS)

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms

  5. Upregulation of Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Gopez, V.; Delis, F.; Michaelides, M.; Grand, D.K.; Wang, G.-J.; Kunos, G.; Volkow, N.D.

    2011-01-01

    The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [{sup 3}H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.

  6. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    International Nuclear Information System (INIS)

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH-) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH- and hepatic ADH-normal (ADH+) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼ 1.5-fold greater in ADH- vs. ADH+ deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH- deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  7. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.

    Science.gov (United States)

    CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. ME Gilbert1, ME Kelly2, S. Salant3, T Shafer1, J Goodman3 1Neurotoxicology Div, US EPA, RTP, NC, 27711, 2Children's Hospital, Philadelphia, PA, 19104, 3Helen Hayes Hospital, Haverstraw, NY, 10993. ...

  8. The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

    Science.gov (United States)

    Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

    2015-09-14

    Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. PMID:26238258

  9. Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Δ9-tetrahydrocannabinol

    International Nuclear Information System (INIS)

    The present study evaluated the consequences of perinatal Δ9-tetrahydrocannabinol (Δ9-THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB1 receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with Δ9-tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, Δ9-THC, or EtOH + Δ9-THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to Δ9-THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB1 receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism

  10. Effect of prenatal exposure to ethanol on the development of cerebral cortex: I. Neuronal generation

    International Nuclear Information System (INIS)

    Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair-fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques. Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1-2 days later for Et-treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1-2 days longer in Et-treated rats. The numbers of neurons generated on a specific day was altered; from GD 12-19 significantly fewer neurons were generated in Et-treated rats than in Ct-treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late-generated neurons in deep cortex of Et-treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et-treated rats tended to be smaller than in Ct-treated rats, particularly early generated neurons in deep cortex. The late-generated neurons in Et-treated rats were of similar size to those in Ct-treated rats despite their abnormal position in deep cortex. Neurons in Ct-treated rats tended to be rounder than those in Et-treated rats which were more polarized in the radial orientation

  11. Anxiogenic-like effects of chronic nicotine exposure in zebrafish.

    Science.gov (United States)

    Stewart, Adam Michael; Grossman, Leah; Collier, Adam D; Echevarria, David J; Kalueff, Allan V

    2015-12-01

    Nicotine is one of the most widely used and abused legal drugs. Although its pharmacological profile has been extensively investigated in humans and rodents, nicotine CNS action remains poorly understood. The importance of finding evolutionarily conserved signaling pathways, and the need to apply high-throughput in vivo screens for CNS drug discovery, necessitate novel efficient experimental models for nicotine research. Zebrafish (Danio rerio) are rapidly emerging as an excellent organism for studying drug abuse, neuropharmacology and toxicology and have recently been applied to testing nicotine. Anxiolytic, rewarding and memory-modulating effects of acute nicotine treatment in zebrafish are consistently reported in the literature. However, while nicotine abuse is more relevant to long-term exposure models, little is known about chronic effects of nicotine on zebrafish behavior. In the present study, chronic 4-day exposure to 1-2mg/L nicotine mildly increased adult zebrafish shoaling but did not alter baseline cortisol levels. We also found that chronic exposure to nicotine evokes robust anxiogenic behavioral responses in zebrafish tested in the novel tank test paradigm. Generally paralleling clinical and rodent data on anxiogenic effects of chronic nicotine, our study supports the developing utility of zebrafish for nicotine research. PMID:25643654

  12. Alterations in mesolimbic dopamine function during the abstinence period following chronic ethanol consumption.

    Science.gov (United States)

    Bailey, C P; O'Callaghan, M J; Croft, A P; Manley, S J; Little, H J

    2001-12-01

    Previous work demonstrated that the locomotor stimulant actions of amphetamine, cocaine and nicotine were increased when these drugs were given during the abstinence phase after chronic ethanol consumption. These changes were seen at 6 days and at 2 months after cessation of alcohol. The present study examined neuronal alterations which might be related to these changes in behaviour. Markedly reduced spontaneous firing rates of dopaminergic cells in the ventral tegmental area (VTA) in midbrain slices were seen 6 days into the abstinence period after cessation of chronic ethanol consumption, but by 2 months the firing rates had returned to control values. Increased affinity of striatal receptors for the D1-like receptor ligand 3H-SCH23390, but no change in the receptor density, was found both at the 6 day and the 2 month intervals. The binding properties of striatal D2-like receptors, of D1-like and D2-like receptors in the frontal cerebral cortex, and the release of tritiated dopamine from slices of striatum or frontal cerebral cortex, were unchanged at 6 days and 2 months. It is suggested that the decreased neuronal firing leads to a persistent increase in sensitivity of D1-like receptors and that these changes could explain the increased effects of the other drugs of abuse. PMID:11747903

  13. An in vitro model for studying the effects of continuous ethanol exposure on N-methyl-d-aspartate receptor function

    OpenAIRE

    Nath, Vikas; Reneau, Jason C.; Dertien, Janet S.; Agrawal, Rajiv G.; Guerra, Ian; Bhakta, Yaminiben; Busari, Kafayat; Neumann, Mary Kate; Bergeson, Susan E.; Popp, R. Lisa

    2011-01-01

    Long-term ethanol exposure has deleterious effects on both glial and neuronal function. We assessed alterations in both astrocytic and neuronal viability, as well as alterations in N-methyl-d-aspartate receptor (NMDAR) function, in co-cultures of rat cerebellar granule cells (CGCs) and astrocytes after continuous ethanol exposure (CEE). Treatment of cells with 100 mM EtOH once every 24 h for four days resulted in a mean ethanol concentration of 57.3 ± 2.1 mM. Comparisons between control and p...

  14. Effect of prenatal ethanol exposure on sexual motivation in adult rats.

    Science.gov (United States)

    Ávila, Mara Aparecida P; Marthos, Gabriela Cristina P; Oliveira, Liliane Gibram M; Figueiredo, Eduardo Costa; Giusti-Paiva, Alexandre; Vilela, Fabiana Cardoso

    2016-08-01

    Maternal alcohol use during pregnancy adversely affects prenatal and postnatal growth and increases the risk of behavioral deficits. The aim of the present study was to evaluate the effect of prenatal exposure to a moderate dose of alcohol on sexual motivation during adulthood. Rats were prenatally exposed to ethanol by feeding pregnant dams a liquid diet containing 25% ethanol-derived calories on days 6 through 19 of gestation. The controls consisted of pair-fed dams (receiving an isocaloric liquid diet containing 0% ethanol-derived calories) and dams with ad libitum access to a liquid control diet. The sexual motivation of offspring was evaluated during adulthood. The results revealed that the male and female pups of dams treated with alcohol exhibited reduced weight gain, which persisted until adulthood. Both male and female adult animals from dams that were exposed to alcohol showed a reduction in the preference score in the sexual motivation test. Taken together, these results provide evidence of the damaging effects of prenatal alcohol exposure on sexual motivation responses in adulthood. PMID:27565750

  15. Sensitivity of Trout to Chronic Acute Exposure to Selenium

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel; Nielsen, M. Gissel

    1978-01-01

    Trout were exposed to selenite (Na2SeO3) solutions of varying concentrations (0.1-100 ppm Se) for periods of up to 4 wk. A chronic exposure to 0.1 ppm Se or less is non-lethal to trout. Lethality at higher concentrations depends on the length of exposure. Trout that survive for 10 days in tap......-water after contamination will not die as a result of Se toxicity and can safely be used for human consumption....

  16. Large-scale analysis of acute ethanol exposure in zebrafish development: a critical time window and resilience.

    Directory of Open Access Journals (Sweden)

    Shaukat Ali

    Full Text Available BACKGROUND: In humans, ethanol exposure during pregnancy causes a spectrum of developmental defects (fetal alcohol syndrome or FAS. Individuals vary in phenotypic expression. Zebrafish embryos develop FAS-like features after ethanol exposure. In this study, we ask whether stage-specific effects of ethanol can be identified in the zebrafish, and if so, whether they allow the pinpointing of sensitive developmental mechanisms. We have therefore conducted the first large-scale (>1500 embryos analysis of acute, stage-specific drug effects on zebrafish development, with a large panel of readouts. METHODOLOGY/PRINCIPAL FINDINGS: Zebrafish embryos were raised in 96-well plates. Range-finding indicated that 10% ethanol for 1 h was suitable for an acute exposure regime. High-resolution magic-angle spinning proton magnetic resonance spectroscopy showed that this produced a transient pulse of 0.86% concentration of ethanol in the embryo within the chorion. Survivors at 5 days postfertilisation were analysed. Phenotypes ranged from normal (resilient to severely malformed. Ethanol exposure at early stages caused high mortality (≥88%. At later stages of exposure, mortality declined and malformations developed. Pharyngeal arch hypoplasia and behavioral impairment were most common after prim-6 and prim-16 exposure. By contrast, microphthalmia and growth retardation were stage-independent. CONCLUSIONS: Our findings show that some ethanol effects are strongly stage-dependent. The phenotypes mimic key aspects of FAS including craniofacial abnormality, microphthalmia, growth retardation and behavioral impairment. We also identify a critical time window (prim-6 and prim-16 for ethanol sensitivity. Finally, our identification of a wide phenotypic spectrum is reminiscent of human FAS, and may provide a useful model for studying disease resilience.

  17. Does chronic exposure to mobile phones affect cognition?

    OpenAIRE

    Mohan, Mamta; Khaliq, Farah; Panwar, Aprajita; Vaney, Neelam

    2016-01-01

    Mobile phones form an integral part of our modern lifestyle. Following the drastic rise in mobile phone use in recent years, it has become important to study its potential public health impact. Amongst the various mobile phone health hazards, the most alarming is the possible effect on the brain. The aim of the present study was to explore whether chronic exposure to mobile phones affects cognition. Ninety subjects aged 17–25 years with normal hearing were recruited for the study and divided ...

  18. Sub-chronic safety evaluation of the ethanol extract of Aralia elata leaves in Beagle dogs.

    Science.gov (United States)

    Li, Fengjin; He, Xiaoli; Niu, Wenying; Feng, Yuenan; Bian, Jingqi; Kuang, Haixue; Xiao, Hongbin

    2016-08-01

    Aralia elata Seem. (A. elata) is a traditional Chinese medicine to treat some diseases. This investigation aims to evaluate the pharmaceutical safety of the ethanol extract of A. elata leaves, namely ethanol leaves extract (ELE), in Beagle dogs. In sub-chronic oral toxicity study, dogs were treated with the ELE at doses of 50, 100 and 200 mg/kg for 12 weeks and followed by 4 weeks recovery period. During experimental period, clinical signs, mortality, body temperature, food consumption and body weight were recorded. Analysis of electrocardiogram, urinalysis, ophthalmoscopy, hematology, serum biochemistry, organ weights and histopathology were performed. The results showed that both food consumption and body weight significantly decreased in high-dose group. Treatment-related side effects and mortality were observed in high-dose female dogs. Some parameters showed significant alterations in electrocardiogram, urinalysis, serum biochemistry and relative organ weights. These alterations were not related to dose or consistent across gender, which were ascribed to incidental and biological variability. The findings in this study indicated that the no-observed adverse effect level (NOAEL) of the ELE was 100 mg/kg in dogs and provided a vital reference for selecting a safe application dosage for human consumption. PMID:27156779

  19. Acute Inhalation Exposure to Titanium Ethanolate as a Possible Cause of Metal Fume Fever

    Directory of Open Access Journals (Sweden)

    M Ahmadimanesh

    2014-04-01

    Full Text Available Occupational inhalation exposure to noxious agents is not uncommon. Herein, we present a 26-year-old male student who had accidental acute inhalation exposure to a large quantity of titanium ethanolate and hydrogen chloride in chemistry lab. He was referred to the emergency department of our hospital with low-grade fever, dyspnea, headache, fatigue and myalgia. After 24 hrs of symptomatic treatment (oxygen therapy and acetaminophen, the fever was subsided and the patient discharged home in a good clinical condition. The presented symptoms could be interpreted as a form of metal fume fever. It can therefore be concluded that organo-metallic compound of titanium metal may have the potential to produce metal fume fever in human.

  20. Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure.

    Science.gov (United States)

    Tolosa, Ezequiel J; Fernández-Zapico, Martín E; Battiato, Natalia L; Rovasio, Roberto A

    2016-01-01

    Our aim was to understand the involvement of Sonic hedgehog (Shh) morphogen in the oriented distribution of neural crest cells (NCCs) toward the optic vesicle and to look for potential disorders of this guiding mechanism after ethanol exposure. In vitro directional analysis showed the chemotactic response of NCCs up Shh gradients and to notochord co-cultures (Shh source) or to their conditioned medium, a response inhibited by anti-Shh antibody, receptor inhibitor cyclopamine and anti-Smo morpholino (MO). Expression of the Ptch-Smo receptor complex on in vitro NCCs was also shown. In whole embryos, the expression of Shh mRNA and protein was seen in the ocular region, and of Ptch, Smo and Gli/Sufu system on cephalic NCCs. Anti-Smo MO or Ptch-mutated plasmid (Ptch1(Δloop2)) impaired cephalic NCC migration/distribution, with fewer cells invading the optic region and with higher cell density at the homolateral mesencephalic level. Beads embedded with cyclopamine (Smo-blocking) or Shh (ectopic signal) supported the role of Shh as an in vivo guide molecule for cephalic NCCs. Ethanol exposure perturbed in vitro and in vivo NCC migration. Early stage embryos treated with ethanol, in a model reproducing Fetal Alcohol Syndrome, showed later disruptions of craniofacial development associated with abnormal in situ expression of Shh morphogen. The results show the Shh/Ptch/Smo-dependent migration of NCCs toward the optic vesicle, with the support of specific inactivation with genetic and pharmacological tools. They also help to understand mechanisms of accurate distribution of embryonic cells and of their perturbation by a commonly consumed teratogen, and demonstrate, in addition to its other known developmental functions, a new biological activity of cellular guidance for Shh. PMID:26979762

  1. Effects in Plant Populations Resulting from Chronic Radiation Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, Stanislav A.; Volkova, Polina Yu.; Vasiliyev, Denis V.; Dikareva, Nina S.; Oudalova, Alla A. [Russian Institute of Agricultural Radiology and Agroecology, 249032, Obninsk (Russian Federation)

    2014-07-01

    Human industrial activities have left behind a legacy of ecosystems strongly impacted by a wide range of contaminants, including radionuclides. Phyto-toxic effects of acute impact are well known, but the consequences of long-term chronic exposure to low pollutant concentrations is neither well understood nor adequately included in risk assessments. To understand effects of real-world contaminant exposure properly we must pay attention to what is actually going on in the field. However, for many wildlife groups and endpoints, there are no, or very few, studies that link accumulation, chronic exposure and biological effects in natural settings. To fill the gaps, results of field studies carried out on different plant species (winter rye and wheat, spring barley, oats, Scots pine, wild vetch, crested hair-grass) in various radioecological situations (nuclear weapon testing, the Chernobyl accident, uranium and radium processing) to investigate effects of long-term chronic exposure to radionuclides are discussed. Because each impacted site developed in its own way due to a unique history of events, the experience from one case study is rarely directly applicable to another situation. In spite of high heterogeneity in response, we have detected several general patterns. Plant populations growing in areas with relatively low levels of pollution are characterized by the increased level of both cytogenetic alterations and genetic diversity. Accumulation of cellular alterations may afterward influence biological parameters important for populations such as health and reproduction. Presented data provide evidence that in plant populations inhabiting heavily contaminated territories cytogenetic damage were accompanied by decrease in reproductive ability. In less contaminated sites, because of the scarcity of data available, it is impossible to establish exactly the relationship between cytogenetic effects and reproductive ability. Radioactive contamination of the plants

  2. A STEREOLOGICAL ANALYSIS OF THE EFFECT OF EARLY POSTNATAL ETHANOL EXPOSURE ON NEURONAL NUMBERS IN RAT DENTATE GYRUS

    Directory of Open Access Journals (Sweden)

    Takanori Miki

    2011-05-01

    Full Text Available Maternal ethanol ingestion during pregnancy can cause fetal alcohol syndrome (FAS in their offspring. Among the symptoms of FAS, damage to the central nervous system has emerged as one of the most serious problems. We have previously shown that a relatively high dose of ethanol exposure during early postnatal life can cause alterations in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rat pups to ethanol during early postnatal life had effects on the total number of the dentate gyrus neurons. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 to 15. Ethanol exposure was achieved by placing rat pups in a chamber containing ethanol vapour for 3 hours a day. The blood ethanol concentration was found to be about 430 mg/dL at the end of the exposure period. Groups of ethanol treated (ET, separation controls (SC and mother reared controls (MRC were anaesthetised and killed at 16-days-of-age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle was used to determine the volume of subdivisions of the dentate gyrus, and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There was, on average, about 421,000 granule cells in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This value was significantly smaller than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. It is concluded that neurons in the hilus region of the dentate gyrus may be particularly vulnerable to the effects of a high dose of ethanol exposure during PND 10-15. It is likely that this deficit was due to neuronal death induced by some mechanisms related to

  3. Chronic treatment with a selective 5-HT6 receptor antagonist alters the behavioral and neurochemical effects of ethanol in young adult rats.

    Science.gov (United States)

    Jayarajan, Pradeep; Nirogi, Ramakrishna; Shinde, Anil; Benade, Vijay; Muddana, Nageswara Rao

    2016-04-01

    Experimental evidence indicates a potential role of 5-HT6 receptors in the regulation of addictive behavior. We studied the effects of a potent and selective 5-HT6 receptor antagonist (compound A) on voluntary ethanol intake and behavioral/neurochemical changes induced by ethanol. The pharmacokinetic interaction of compound A and ethanol was assessed. The effect of compound A on schedule-induced ethanol polydipsia was studied to determine its effect on voluntary ethanol intake. Open-field and ethanol-induced loss of righting reflex assays were carried out to determine the effect of compound A on the ataxic and sedative effects of ethanol. The effect on motor learning was evaluated using rotarod and brain microdialysis was carried out to study the effect on monoaminergic neurotransmission. No significant changes were observed in the pharmacokinetic parameters of compound A when cotreated with ethanol. Compound A significantly decreased voluntary ethanol consumption and attenuated the effects of ethanol on motor learning. Compound A also antagonized the sedative and ataxic effects of ethanol. The effect of ethanol on the dopaminergic and noradrenergic neurotransmission was blocked by compound A. The effects of compound A were evident only after chronic treatment. Compound A may have attenuated the behavioral effects of ethanol by blocking the ethanol-induced efflux of dopamine and norepinephrine in the motor cortex. PMID:25932717

  4. Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: Effects on striatal dopamine and opioid systems in C57BL/6J mice

    OpenAIRE

    Yong ZHANG; Schlussman, Stefan D; Rabkin, Jacqui; Butelman, Eduardo R.; Ho, Ann; Kreek, Mary Jeanne

    2012-01-01

    Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an “addiction-like cycle” in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal /13-day saline + 1-d...

  5. Effect of acute and chronic ethanol pre-treatment on the disposition of phencyclidine (PCP) in the rat.

    Science.gov (United States)

    Vadlamani, N L; Pontani, R B; Misra, A L

    1982-05-01

    Disposition of [H] Phencyclidine in brain, plasma and adipose tissue of rats acutely and chronically-treated with ethanol was studied using a method possessing high sensitivity and specificity for PCP. In rats acutely-treated with ethanol (5 g/kg PO dose) and PCP (10 mg/kg IP dose), dispositional factors did not play a role in the intensifies pharmacological and behavioral effects of PCP. However in rats chronically-treated with 2.5 g/kg PO dose of ethanol twice a day for 19 days, the disposition of PCP (5 mg/kg IP dose) was significantly altered and the values of PCP in brain, plasma and adipose tissue were significantly higher than those in the control group. Although inhibition of PCP metabolism and a comparatively slower rate of its elimination appear to account for the potentiation of drug effects in animals chronically-treated with ethanol, interaction of drugs at the level of the central nervous system cannot be ruled out. PMID:7089042

  6. Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury.

    Science.gov (United States)

    Duncan, Jeremy W; Zhang, Xiao; Wang, Niping; Johnson, Shakevia; Harris, Sharonda; Udemgba, Chinelo; Ou, Xiao-Ming; Youdim, Moussa B; Stockmeier, Craig A; Wang, Jun Ming

    2016-06-01

    Binge drinking induces several neurotoxic consequences including oxidative stress and neurodegeneration. Because of these effects, drugs which prevent ethanol-induced damage to the brain may be clinically beneficial. In this study, we investigated the ethanol-mediated KLF11-MAO cell death cascade in the frontal cortex of Sprague-Dawley rats exposed to a modified Majchowicz 4-day binge ethanol model and control rats. Moreover, MAO inhibitors (MAOIs) were investigated for neuroprotective activity against binge ethanol. Binge ethanol-treated rats demonstrated a significant increase in KLF11, both MAO isoforms, protein oxidation and caspase-3, as well as a reduction in BDNF expression in the frontal cortex compared to control rats. MAOIs prevented these binge ethanol-induced changes, suggesting a neuroprotective benefit. Neither binge ethanol nor MAOI treatment significantly affected protein expression levels of the oxidative stress enzymes, SOD2 or catalase. Furthermore, ethanol-induced antinociception was enhanced following exposure to the 4-day ethanol binge. These results demonstrate that the KLF11-MAO pathway is activated by binge ethanol exposure and MAOIs are neuroprotective by preventing the binge ethanol-induced changes associated with this cell death cascade. This study supports KLF11-MAO as a mechanism of ethanol-induced neurotoxicity and cell death that could be targeted with MAOI drug therapy to alleviate alcohol-related brain injury. Further examination of MAOIs to reduce alcohol use disorder-related brain injury could provide pivotal insight to future pharmacotherapeutic opportunities. PMID:26805422

  7. Developmental ethanol exposure-induced sleep fragmentation predicts adult cognitive impairment.

    Science.gov (United States)

    Wilson, D A; Masiello, K; Lewin, M P; Hui, M; Smiley, J F; Saito, M

    2016-05-13

    Developmental ethanol (EtOH) exposure can lead to long-lasting cognitive impairment, hyperactivity, and emotional dysregulation among other problems. In healthy adults, sleep plays an important role in each of these behavioral manifestations. Here we explored circadian rhythms (activity, temperature) and slow-wave sleep (SWS) in adult mice that had received a single day of EtOH exposure on postnatal day 7 and saline littermate controls. We tested for correlations between slow-wave activity and both contextual fear conditioning and hyperactivity. Developmental EtOH resulted in adult hyperactivity within the home cage compared to controls but did not significantly modify circadian cycles in activity or temperature. It also resulted in reduced and fragmented SWS, including reduced slow-wave bout duration and increased slow-wave/fast-wave transitions over 24-h periods. In the same animals, developmental EtOH exposure also resulted in impaired contextual fear conditioning memory. The impairment in memory was significantly correlated with SWS fragmentation. Furthermore, EtOH-treated animals did not display a post-training modification in SWS which occurred in controls. In contrast to the memory impairment, sleep fragmentation was not correlated with the developmental EtOH-induced hyperactivity. Together these results suggest that disruption of SWS and its plasticity are a secondary contributor to a subset of developmental EtOH exposure's long-lasting consequences. PMID:26892295

  8. Impacts of chronic sublethal exposure to clothianidin on winter honeybees.

    Science.gov (United States)

    Alkassab, Abdulrahim T; Kirchner, Wolfgang H

    2016-07-01

    A wide application of systemic pesticides and detection of their residues in bee-collected pollen and nectar at sublethal concentrations led to the emergence of concerns about bees' chronic exposure and possible sublethal effects on insect pollinators. Therefore, special attention was given to reducing unintentional intoxications under field conditions. The sensitivity of winter bees throughout their long lifespan to residual exposure of pesticides is not well known, since most previous studies only looked at the effects on summer bees. Here, we performed various laboratory bioassays to assess the effects of clothianidin on the survival and behavior of winter bees. Oral lethal and sublethal doses were administered throughout 12-day. The obtained LD50 values at 48, 72, 96 h and 10 days were 26.9, 18.0, 15.1 and 9.5 ng/bee, respectively. Concentrations <20 µg/kg were found to be sublethal. Oral exposure to sublethal doses was carried out for 12-day and, the behavioral functions were tested on the respective 13th day. Although slight reductions in the responses at the concentrations 10 and 15 µg/kg were observed, all tested sublethal concentrations had showed non-significant effects on the sucrose responsiveness, habitation of the proboscis extension reflex and olfactory learning performance. Nevertheless, chronic exposure to 15 µg/kg affected the specificity of the early long-term memory (24 h). Since the tested concentrations were in the range of field-relevant concentrations, our results strongly suggest that related-effects on winter and summer bees' sensitivity should also be studied under realistic conditions. PMID:27090425

  9. The effects of prepubertal gonadectomy and binge-like ethanol exposure during adolescence on ethanol drinking in adult male and female rats

    OpenAIRE

    Sherrill, Luke K.; Koss, Wendy A.; Foreman, Emily S.; Gulley, Joshua M.

    2010-01-01

    The pubertal surge in gonadal hormones that occurs during adolescence may impact the long-term effects of early alcohol exposure and sex differences in drinking behavior in adulthood. We investigated this hypothesis by performing sham or gonadectomy surgeries in Long Evans rats around postnatal day (P) 20. From P35–45, males and females were given saline or 3.0 g/kg ethanol using a binge-like model of exposure (8 injections total). As adults (P100), they were trained to self-administer ethano...

  10. Repeated ethanol exposure affects the acquisition of spatial memory in adolescent female rats

    OpenAIRE

    Sircar, Ratna; Basak, Ashim K.; Sircar, Debashish

    2009-01-01

    Ethanol has been reported to disrupt spatial learning and memory in adolescent male rats. The present study was undertaken to determine the effects of ethanol on the acquisition of spatial memory in adolescent female rats. Adolescent female rats were subjected to repeated ethanol or saline treatments, and spatial learning was tested in the Morris water maze. For comparison, adult female rats were subjected to similar ethanol treatment and behavioral assessments as for adolescent rats. Ethanol...

  11. Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: effects on striatal dopamine and opioid systems in C57BL/6J mice.

    Science.gov (United States)

    Zhang, Yong; Schlussman, Stefan D; Rabkin, Jacqui; Butelman, Eduardo R; Ho, Ann; Kreek, Mary Jeanne

    2013-04-01

    Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an "addiction-like cycle" in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal/13-day saline + 1-day cocaine), chronic cocaine exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day withdrawal/14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection × 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered, modeling initial exposure. In "re-exposure" groups, after a 14-day injection-free period (modeling abstinence/withdrawal), mice that had received cocaine were re-injected with 14-day escalating-dose binge cocaine, whereas controls received saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to determine striatal dopamine content. Messenger RNA levels of preprodynorphin (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day escalating exposure or re-exposure than in those in the acute cocaine group and controls. Pdyn mRNA levels were higher in the cocaine groups than in controls. Long-term adaptation was observed across the stages of this addiction-like cycle, in that the effects of cocaine on dopamine levels were increased after re-exposure compared to exposure. Changes in striatal dopaminergic responses across chronic escalating cocaine exposure and re-exposure are a central feature of the neurobiology of relapsing addictive states. PMID:23164614

  12. Lead exposure increases oxidative stress in the gastric mucosa of HCI/ethanol-exposed rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the role of reactive oxygen species in the ulcer-aggravating effect of lead in albino rats.METHODS: Albino Wistar rats were randomly divided into three groups and treated orally with 100 mg/L (low dose) or 5000 mg/L (high dose) of lead acetate for 15 wk. A third group received saline and served as control.At the end of wk 15, colorimetric assays were applied to determine the concentrations of total protein and nitrite, the activities of the oxidative enzymes catalase and superoxide dismutase, and lipid peroxidation in homogenized gastric mucosal samples.RESULTS: Exposure of rats to lead significantly increased the gastric mucosal damage caused by acidified ethanol. Although the basal gastric acid secretory rate was not significantly altered, the maximal response of the stomach to histamine was significantly higher in the lead-exposed animals than in the unexposed control group. Exposure to low and high levels of lead significantly increased gastric lipid peroxidation to 183.2% ± 12.7% and 226.1% ± 6.8% of control values respectively (P < 0.0). On the other hand, lead exposure significantly decreased catalase and superoxide dismutase (SOD) activities and the amount of nitrite in gastric mucosal samples.CONCLUSION: Lead increases the formation of gastric ulcers by interfering with the oxidative metabolism in the stomach.

  13. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus- indica mucilage

    Institute of Scientific and Technical Information of China (English)

    Ricardo Vázquez-Ramírez; Marisela Olguín-Martínez; Carlos Kubli-Garfias; Rolando Hernández-Mu(n)oz

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats.METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined.Histological studies of gastric samples from the experimental groups were included.RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes.Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect.The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes.CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids,mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  14. Laparoscopic Uterine Nerve Ethanol Neurolysis (LUNEN in Patients with Chronic Pelvic Pain

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    Seyhan Sönmez

    2016-03-01

    Full Text Available Objective: To investigate the efficacy of laparoscopic uterine nerve ethanol neurolysis (LUNEN for pain man­agement in patients with chronic pelvic pain (CPP. Methods: LUNEN, as a chemical neurolysis procedure, was performed on 22 subjects, and these were com­pared with 20 controls that had a diagnostic laparoscopy alone. Pre-treatment and postoperative 6th month Visual Analogue Scale (VAS scores were estimated and a sub­jective pain evaluation questioning patients’ satisfaction about pain relief in the 6th month after surgery was also performed. Results: A total of 31 (73.8% out of 42 CPP patients had a laparoscopic pelvic pathology. Preoperative VAS scores were similar in the groups; however, the mean postop­erative VAS score was significantly lower in the LUNEN group than in the control group (3.18 ± 2.88 vs. 5.35 ± 3.09; p=0.02. In the LUNEN group, the number of pa­tients who stated that their pain was relieved partially or completely was also significantly higher than in the con­trol group (82% vs. 40%, p=0.019. Conclusion: LUNEN is a feasible, safe and effective sur­gical alternative to traditional surgical methods in patients suffering from CPP. J Clin Exp Invest 2016; 7 (1: 7-13

  15. Chronic Ethanol Feeding Modulates Inflammatory Mediators, Activation of Nuclear Factor-κB, and Responsiveness to Endotoxin in Murine Kupffer Cells and Circulating Leukocytes

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    Miriam Maraslioglu

    2014-01-01

    Full Text Available Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κBEGFP reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS. We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.

  16. CCL2-ethanol interactions and hippocampal synaptic protein expression in a transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Donna eGruol

    2014-04-01

    Full Text Available Chronic exposure to ethanol produces a number of detrimental effects on behavior. Neuroadaptive changes in brain structure or function underlie these behavioral changes and may be transient or persistent in nature. Central to the functional changes are alterations in the biology of neuronal and glial cells of the brain. Recent data show that ethanol induces glial cells of the brain to produce elevated levels of neuroimmune factors including CCL2, a key innate immune chemokine. Depending on the conditions of ethanol exposure, the upregulated levels of CCL2 can be transient or persistent and outlast the period of ethanol exposure. Importantly, results indicate that the upregulated levels of CCL2 may lead to CCL2-ethanol interactions that mediate or regulate the effects of ethanol on the brain. Glial cells are in close association with neurons and regulate many neuronal functions. Therefore, effects of ethanol on glial cells may underlie some of the effects of ethanol on neurons. To investigate this possibility, we are studying the effects of chronic ethanol on hippocampal synaptic function in a transgenic mouse model that expresses elevated levels of CCL2 in the brain through enhanced glial expression, a situation know to occur in alcoholics. Both CCL2 and ethanol have been reported to alter synaptic function in the hippocampus. In the current study, we determined if interactions are evident between CCL2 and ethanol at level of hippocampal synaptic proteins. Two ethanol exposure paradigms were used; the first involved ethanol exposure by drinking and the second involved ethanol exposure in a paradigm that combines drinking plus ethanol vapor. The first paradigm does not produce dependence on ethanol, whereas the second paradigm is commonly used to produce ethanol dependence. Results show modest effects of both ethanol exposure paradigms on the level of synaptic proteins in the hippocampus of CCL2 transgenic mice compared with their non

  17. Memory Deficit Recovery after Chronic Vanadium Exposure in Mice

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    Oluwabusayo Folarin

    2016-01-01

    Full Text Available Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

  18. Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

    Science.gov (United States)

    Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

    2008-12-01

    Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring. PMID:18713641

  19. Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase Ⅳ expression in nucleus accumbens of rats: naloxone reversal

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Wei-liang BIAN; Gui-qin XIE; Sheng-zhong CUI; Mei-ling WU; Yue-hua LI; Ling-li QUE; Xiao-ru YUAN

    2008-01-01

    Aim: To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase Ⅳ (CaM kinase Ⅳ) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of non-selective opioid antagonist (naloxone) on the CaM kinase Ⅳ expression in the NAc and ethanol consumption of rats were also observed. Methods: Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase Ⅳ levels in the NAc were analyzed using Western blotting. Results: Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase Ⅳ expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenu-ated ethanol intake of rats and antagonized the decrease of CaM kinase Ⅳ in the nuclei of NAc neurons. The cytosolic CaM kinase Ⅳ protein levels of the NAc also increased in rats exposed to ethanol plus naloxone. Conclusion: Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase Ⅳ signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase Ⅳ in the NAc.

  20. Survival and concanavalin-A-induced capping in CHO fibroblasts after exposure to hyperthermia, ethanol, and x irradiation

    International Nuclear Information System (INIS)

    Two parameters, concanavalin-A-induced capping and clonogenicity, were examined in HA-1 fibroblasts after exposure to heat, ethanol, x irradiation, and heat plus deuterium oxide. Capping and clonogenicity were shown to decrease over time in samples exposed to 43, 44, and 450C, while both parameters remained unaffected at 37, 41, and 420C. Ethanol exposure showed a survival decrease at a concentration of 8% but no significant effect on survival at 4, 6, and 7%. Capping, however, decreased over time at ethanol concentrations of 6, 7, and 8%. X irradiation had no effect on capping over a dose range of 0 to 1400 rad, while survival was markedly decreased. At 370C, exposure to 20, 40, and 80% deuterium oxide showed no effect on either survival or capping. However, at 430C, the same concentrations of deuterium oxide markedly increased both capping and clonogenicity over that of cells exposed to 430C without deuterium oxide. Potential mechanisms accounting for the heat- and ethanol-induced impairment of capping ability are inhibition of cellular energy metabolism and/or alteration of plasma membrane composition

  1. Exposure of precision-cut rat liver slices to ethanol accelerates fibrogenesis

    OpenAIRE

    Schaffert, Courtney S.; Duryee, Michael J.; Bennett, Robert G; DeVeney, Amy L; Tuma, Dean J; Olinga, Peter; Easterling, Karen C.; Thiele, Geoffrey M.; Klassen, Lynell W

    2010-01-01

    Ethanol metabolism in the liver induces oxidative stress and altered cytokine production preceding myofibroblast activation and fibrogenic responses. The purpose of this study was to determine how ethanol affects the fibrogenic response in precision-cut liver slices (PCLS). PCLS were obtained from chow-fed male Wistar rats (200–300 g) and were cultured up to 96 h in medium, 25 mM ethanol, or 25 mM ethanol and 0.5 mM 4-methylpyrazole (4-MP), an inhibitor of ethanol metabolism. Slices from ever...

  2. Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain.

    Directory of Open Access Journals (Sweden)

    Ryan P Vetreno

    Full Text Available During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55 treatment led to persistent, global reductions of choline acetyltransferase (ChAT expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70 produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28-P48 and adult (P70-P90 binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity.

  3. Pre- and Postnatal Exposure to Moderate Levels of Ethanol Can Have Long-Lasting Effects on Hippocampal Glutamate Uptake in Adolescent Offspring

    OpenAIRE

    Brolese, Giovana; Lunardi, Paula; de Souza, Daniela F.; Fernanda M. Lopes; Leite, Marina C.; Gonçalves, Carlos-Alberto

    2015-01-01

    The developing brain is vulnerable to the effects of ethanol. Glutamate is the main mediator of excitatory signals in the brain and is probably involved in most aspects of normal brain function during development. The aim of this study was to investigate vulnerability to and the impact of ethanol toxicity on glutamate uptake signaling in adolescent rats after moderate pre and postnatal ethanol exposure. Pregnant female rats were divided into three groups and treated only with water (control),...

  4. Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: Relationship to structural plasticity and immediate early gene expression in frontal cortex

    OpenAIRE

    Derek A Hamilton; Akers, Katherine G.; Rice, James P.; Johnson, Travis E.; Candelaria-Cook, Felicha T.; Maes, Levi I.; Rosenberg, Martina; Valenzuela, C. Fernando; Savage, Daniel D.

    2009-01-01

    The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Rep...

  5. The Zebrafish, a Novel Model Organism for Screening Compounds Affecting Acute and Chronic Ethanol-Induced Effects.

    Science.gov (United States)

    Tran, S; Facciol, A; Gerlai, R

    2016-01-01

    Alcohol addiction is a major unmet medical and economic issue for which very few efficacious pharmacological treatment options are currently available. The development and identification of new compounds and drugs to treat alcohol addiction is hampered by the high costs and low amenability of traditional laboratory rodents to high-throughput behavioral screens. The zebrafish represents an excellent compromise between systems complexity and practical simplicity by overcoming many limitations inherent in these rodent models. In this chapter, we review current advances in the behavioral and neurochemical characterization of ethanol-induced changes in zebrafish. We also discuss the basic principles and methods of and the most recent advances in using paradigms with which one can screen for compounds altering acute and chronic ethanol-induced effects in zebrafish. PMID:27055623

  6. Influences of acute ethanol exposure on locomotor activities of zebrafish larvae under different illumination.

    Science.gov (United States)

    Guo, Ning; Lin, Jia; Peng, Xiaolan; Chen, Haojun; Zhang, Yinglan; Liu, Xiuyun; Li, Qiang

    2015-11-01

    Larval zebrafish present unique opportunities to study the behavioral responses of a model organism to environmental challenges during early developmental stages. The purpose of the current study was to investigate the locomotor activities of AB strain zebrafish larvae at 5 and 7 days post-fertilization (dpf) in response to light changes under the influence of ethanol, and to explore potential neurological mechanisms that are involved in ethanol intoxication. AB strain zebrafish larvae at both 5 and 7 dpf were treated with ethanol at 0% (control), 0.1%, 0.25%, 0.5%, 1%, and 2% (v/v%). The locomotor activities of the larvae during alternating light-dark challenges, as well as the locomotor responses immediately following the light transitions, were investigated. The levels of various neurotransmitters were also measured in selected ethanol-treated groups. The larvae at 5 and 7 dpf demonstrated similar patterns of locomotor responses to ethanol treatment. Ethanol treatment at 1% increased the swimming distances of the zebrafish larvae in the dark periods, but had no effect on the swimming distances in the light periods. In contrast, ethanol treatment at 2% increased the swimming distances in the light periods, but did not potentiate the swimming activity in the dark periods, compared to controls. Differences in the levels of neurotransmitters that are involved in norepinephrine, dopamine, and serotonin pathways were also observed in groups with different ethanol treatments. These results indicated the behavioral studies concerning the ethanol effects on locomotor activities of zebrafish larvae could be carried out as early as 5 dpf. The 1% and 2% ethanol-treated zebrafish larvae modeled ethanol effects at different intoxication states, and the differences in neurotransmitter levels suggested the involvement of various neurotransmitter pathways in different ethanol intoxication states. PMID:26384924

  7. Chronic obstructive pulmonary disease (COPD and occupational exposures

    Directory of Open Access Journals (Sweden)

    Zeni Elena

    2006-06-01

    Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is one of the leading causes of morbidity and mortality in both industrialized and developing countries. Cigarette smoking is the major risk factor for COPD. However, relevant information from the literature published within the last years, either on general population samples or on workplaces, indicate that about 15% of all cases of COPD is work-related. Specific settings and agents are quoted which have been indicated or confirmed as linked to COPD. Coal miners, hard-rock miners, tunnel workers, concrete-manufacturing workers, nonmining industrial workers have been shown to be at highest risk for developing COPD. Further evidence that occupational agents are capable of inducing COPD comes from experimental studies, particularly in animal models. In conclusion, occupational exposure to dusts, chemicals, gases should be considered an established, or supported by good evidence, risk factor for developing COPD. The implications of this substantial occupational contribution to COPD must be considered in research planning, in public policy decision-making, and in clinical practice.

  8. Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats.

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    Shiliang Li

    Full Text Available BACKGROUND: Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1 to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2 to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation. METHODS: Rats received saline or ethanol (3.45 g/kg, ip. We evaluated both the mechanical and electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma cardiac troponin-T and glucose-levels were measured and histological examination of the myocardium was performed. In addition, heart transplantation was performed, in which donors received ethanol 6 h or 24 h prior to explantation. Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS-concentration was measured; mRNA and protein expression was assessed by quantitative real-time PCR and Western blot, respectively. RESULTS: Ethanol administration resulted in decreased load-dependent (-34 ± 9% and load-independent (-33 ± 12% contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1 h, which were reversed to the level of controls after 6 h and 24 h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24 h. Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol injection. ST-segment elevation (+47 ± 10%, elongated QT-interval (+38 ± 4%, enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24 h following ethanol-exposure. After heart transplantation, decreased myocardial

  9. Inhibition of long myosin light-chain kinase activation alleviates intestinal damage after binge ethanol exposure and burn injury

    OpenAIRE

    Zahs, Anita; Bird, Melanie D.; Ramirez, Luis; Turner, Jerrold R; Choudhry, Mashkoor A.; Kovacs, Elizabeth J

    2012-01-01

    Laboratory evidence suggests that intestinal permeability is elevated following either binge ethanol exposure or burn injury alone, and this barrier dysfunction is further perturbed when these insults are combined. We and others have previously reported a rise in both systemic and local proinflammatory cytokine production in mice after the combined insult. Knowing that long myosin light-chain kinase (MLCK) is important for epithelial barrier maintenance and can be activated by proinflammatory...

  10. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    International Nuclear Information System (INIS)

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  11. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  12. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    International Nuclear Information System (INIS)

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression

  13. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    Directory of Open Access Journals (Sweden)

    C.L. Castro

    2013-12-01

    Full Text Available The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40 was performed to determine survival rates. Experiment 2 (n=69 was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10 was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001. Experiment 2 showed increased tumor necrosis factor alpha (TNF-α and decreased interleukin-6 (IL-6 and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

  14. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Castro, C.L. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Aguiar-Nemer, A.S. [Departamento de Nutrição, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG (Brazil); Castro-Faria-Neto, H.C. [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ (Brazil); Barros, F.R. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Rocha, E.M.S. [Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Silva-Fonseca, V.A. [Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2013-12-10

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

  15. Late health effects of chronic radiation exposure of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Yarmoshenko, Ilia V.; Malinovsky, Georgy P.; Konshina, Lidia G.; Zhukovsky, Michael V. [Institute of Industrial Ecology UB RAS, 620219, 20, Sophy Kovalevskoy St., Ekaterinburg (Russian Federation); Tuzankina, Irina A. [Institute of Immunology and Physiology UB RAS, 620049, 106, Pervomayskaya St., Ekaterinburg (Russian Federation)

    2014-07-01

    infectious etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

  16. Late health effects of chronic radiation exposure of bone marrow

    International Nuclear Information System (INIS)

    etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

  17. Temperature modulates phototrophic periphyton response to chronic copper exposure.

    Science.gov (United States)

    Lambert, Anne Sophie; Dabrin, Aymeric; Morin, Soizic; Gahou, Josiane; Foulquier, Arnaud; Coquery, Marina; Pesce, Stéphane

    2016-01-01

    Streams located in vineyard areas are highly prone to metal pollution. In a context of global change, aquatic systems are generally subjected to multi-stress conditions due to multiple chemical and/or physical pressures. Among various environmental factors that modulate the ecological effects of toxicants, special attention should be paid to climate change, which is driving an increase in extreme climate events such as sharp temperature rises. In lotic ecosystems, periphyton ensures key ecological functions such as primary production and nutrient cycling. However, although the effects of metals on microbial communities are relatively well known, there is scant data on possible interactions between temperature increase and metal pollution. Here we led a study to evaluate the influence of temperature on the response of phototrophic periphyton to copper (Cu) exposure. Winter communities, collected in a 8 °C river water, were subjected for six weeks to four thermal conditions in microcosms in presence or not of Cu (nominal concentration of 15 μg L(-1)). At the initial river temperature (8 °C), our results confirmed the chronic impact of Cu on periphyton, both in terms of structure (biomass, distribution of algal groups, diatomic composition) and function (photosynthetic efficiency). At higher temperatures (13, 18 and 23 °C), Cu effects were modulated. Indeed, temperature increase reduced Cu effects on algal biomass, algal class proportions, diatom assemblage composition and photosynthetic efficiency. This reduction of Cu effects on periphyton may be related to lower bioaccumulation of Cu and/or to selection of more Cu-tolerant species at higher temperatures. PMID:26608872

  18. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreased lung elastance

    OpenAIRE

    Hartney, John M.; Chu, HongWei; Pelanda, Roberta; Torres, Raul M.

    2012-01-01

    Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks) exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmo...

  19. Effects of Chronic Manganese Exposure on Cognitive and Motor Functioning in Non-Human Primates

    OpenAIRE

    Schneider, Jay S.; Decamp, Emmanuel; Koser, Amy Jo; Fritz, Stephanie; Gonczi, Heather; Syversen, Tore; Guilarte, Tomás R.

    2006-01-01

    Acute exposure to manganese is associated with complex behavioral/psychiatric signs that may include Parkinsonian motor features. However, little is known about the behavioral consequences of chronic manganese exposures. In this study, cynomolgus macaque monkeys were exposed to manganese sulfate (10 –15 mg/kg/week) over an exposure period lasting 272 ± 17 days. Prior to manganese exposure, animals were trained to perform tests of cognitive and motor functioning and overall behavior was assess...

  20. Protective Effect of Natural Honey, Urtica diocia and Their Mixture against Oxidative Stress Caused by Chronic Ethanol Consumption.

    Directory of Open Access Journals (Sweden)

    G.M.F Edrees*, F.G.EL-Said and E.T.Salem

    2007-06-01

    Full Text Available Background: There is increasing implicating oxidative stress in the pathogenesis of chronic pancreatitis. The aim of this study is to investigate affect alcohol addiction and role of some protecting agent. Material and methods: Forty eight rats (Rattus norvigicus were divided into 8 groups. Honey (2.5 g /kg b.w, Urtica dioica (250 mg/kg and Alcohol orally administered at dose (20% exceeds by 2.5% weekly. Results: Ethanol feeding results in increasing serum glucose, total lipids, cholesterol, Low Density Lipoprotein (LDL, triglycerides, urea, liver Glucose-6-Phosphatase (G6Pase, pancreas and liver Malondialdehyde (MDA, Protein Carbonyl (PC. While a decrease were noted in serum insulin, High Density Lipoprotein (HDL, total Protein, Na, K, Ca, Mg, Cu, liver glycogen, pancreas and liver Glucose-6-Phosphate Dehydrogenase (G6PD, Glutathione-S-Transferase (GST, Reduced Glutathione (GSH, Catalase (CAT, Superoxide Dismutase (SOD. Conclusion: Administration of honey, urtica or both with alcohol prevent to great extent the lesions caused by only chronic alcohol administration. Consequently, honey and urtica administration are useful to minimize the hazardous effects resulting from ethanol abuse

  1. Effects of ethanol on voltage-sensitive Na-channels in cultured skeletal muscle: Up-regulation as a result of chronic treatment

    International Nuclear Information System (INIS)

    The effects of acute and chronic treatment with ethanol were studied on the number and activity of tetrodotoxin-sensitive Na-channels in cultured rat skeletal muscle. The number of channels was determined by measurements of specific binding of [3H] saxitoxin (STX) in whole cell preparations. Measurements were also made of the frequency and rate of rise of spontaneously occurring action potentials, which are the physiologic expression of Na-channel density. Acute ethanol (37.5-150 mM), while causing depolarization of membrane potential and blockade of electrical activity, was without effect on specific STX binding. Neither methanol, acetaldehyde nor ethylene glycol had significant effects on these properties when given acutely in the same concentrations as ethanol. Chronic ethanol caused dose-related increases in STX binding and action potential properties with maximal levels being attained after 3 days of treatment at a concentration of 150 mM. On removal of ethanol from the culture medium all properties returned to control levels after 48 hr. Both increased external K+ and tetrodotoxin, which up-regulate Na-channels by reducing cytosolic Ca++, potentiated the ethanol-induced increase in Na-channel density. The increase in STX binding was not associated with changes in affinity of the binding sites for the ligand but was completely prevented by treatment with cycloheximide and actinomycin D. The results demonstrate that ethanol interacts with the cell membrane to induce synthesis of STX-binding sites

  2. Biomarkers for assessing potential carcinogenic effects of chronic arsenic exposure in Inner Mongolia, CHINA

    Science.gov (United States)

    Arsenic is ubiquitous in the environment. Chronic arsenic exposure via drinking water has been associated. with carcinogenic, cardiovascular, neurological and diabetic effects in humans and has been of great public health concern worldwide. In 2001, U.S. Environmental Protection ...

  3. Effect of chronic ethanol administration on iron metabolism in the rat

    International Nuclear Information System (INIS)

    This study shows that the ingestion of ethanol provokes alterations in iron metabolism which may lead to iron overload. Impaired release of reticuloendothelial iron was shown by a decrease of the maximum red blood cell utilization when radioactive iron was supplied as colloidal iron. An impairment in the erythropoietic activity of ethanoltreated animals was also observed, as can be seen from the reduced plasma iron turnover and red blood cell utilization within 24 h of iron administration. A rise in marrow transit time was also observed. In ethanol-treated rats there was an increase in the amount of iron retained both in the liver and the spleen. This was observed in both sexes and also in the offspring from ethanol-treated mothers. (author)

  4. Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: Relationship to structural plasticity and immediate early gene expression in frontal cortex

    Science.gov (United States)

    Hamilton, Derek A.; Akers, Katherine G.; Rice, James P.; Johnson, Travis E.; Candelaria-Cook, Felicha T.; Maes, Levi I.; Rosenberg, Martina; Valenzuela, C. Fernando; Savage, Daniel D.

    2009-01-01

    The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Repeated experience with novel cage-mates resulted in comparable increases in wrestling and social investigation among saccharin- and ethanol-exposed females, whereas social behavioral effects among males were more evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed profound increases in wrestling when social interaction was motivated by 24 hours of isolation. Baseline decreases in dendritic length and spine density in AID were observed in ethanol-exposed rats that were always housed with the same cage-mate. Modest experience-related decreases in dendritic length and spine density in AID were observed in saccharin-exposed rats housed with various cage-mates. In contrast, fetal-ethanol-exposed rats displayed experience-related increases in dendritic length in AID, and no experience-related changes in spine density. The only effect observed in Cg3 was a baseline increase in basilar dendritic length among male ethanol-exposed rats. Robust increases in activity-related IEG expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social interaction in saccharin-exposed rats, however, activity-related increases in IEG expression were not observed in fetal-ethanol-exposed rats in either region. The results indicate that deficits in social behavior are among the long-lasting behavioral consequences of moderate ethanol exposure during brain development, and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social behavior

  5. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    OpenAIRE

    Yongke Lu; Cederbaum, Arthur I.

    2015-01-01

    Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current re...

  6. The Impact of Chronic Pesticide Exposure on Neuropsychological Functioning

    Science.gov (United States)

    Schultz, Caitlin G.; Ferraro, F. Richard

    2013-01-01

    This study compared neuropsychological test performance of individuals (n = 18) with an occupational history of pesticide exposure to individuals (n = 35) with no such exposure history. Results showed that a history of pesticide-related occupation exposure led to deficits in only Digit Symbol performance. Additionally, the correlation between…

  7. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro

    OpenAIRE

    Scherzad, Agmal; HACKENBERG, STEPHAN; FROELICH, KATRIN; RAK, KRISTEN; HAGEN, RUDOLF; TAEGER, JOHANNES; BREGENZER, MAXIMILLIAN; KLEINSASSER, NORBERT

    2016-01-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induc...

  8. Inflammatory and Remodeling Events in Asthma with Chronic Exposure to House Dust Mites: A Murine Model

    OpenAIRE

    Ahn, Joong Hyun; Kim, Chi Hong; Kim, Yong Hyun; Kim, Seung Joon; Lee, Sook-Young; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Song, Jeong Sup; Park, Sung Hak; Kwon, Soon Seog

    2007-01-01

    Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twen...

  9. Effect of Chronic Exposure to Acidic Environment on Radiosensitivity of Gliosarcoma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sora; Kim, Eunhee [Seoul National Univ., Seoul (Korea, Republic of)

    2014-05-15

    In this study, the chronic exposure of cells to acid culture medium, prior or posterior to irradiation, has been investigated for its effect on clonogenic cell survival. Unconventional high-dose radiation therapy, such as SRS, SBRT and MRT, may cause severe vascular damage in tumors, thereby a number of tumor cells facing chronic hypoxia and thus acidosis. According to our observation, gliosarcoma cells become more vulnerable to radiation damage by chronic exposure to acidic condition before irradiation. The longer the preirradiation exposure is, the more vulnerable to radiation damage the cells become. However, the repair of PLD by post-irradiation exposure to acid medium is efficient enough to eliminate the difference in number of the cells carrying PLDs due to different durations of preirradiation exposure to acidic condition.

  10. A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

    Science.gov (United States)

    Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

    2012-01-01

    The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

  11. Chronic ethanol consumption disrupts the core molecular clock and diurnal rhythms of metabolic genes in the liver without affecting the suprachiasmatic nucleus.

    Directory of Open Access Journals (Sweden)

    Ashley N Filiano

    Full Text Available Chronic ethanol consumption disrupts several metabolic pathways including β-oxidation and lipid biosynthesis, facilitating the development of alcoholic fatty liver disease. Many of these same metabolic pathways are directly regulated by cell autonomous circadian clocks, and recent studies suggest that disruption of daily rhythms in metabolism contributes to multiple common cardiometabolic diseases (including non-alcoholic fatty liver disease. However, it is not known whether ethanol disrupts the core molecular clock in the liver, nor whether this, in turn, alters rhythms in lipid metabolism. Herein, we tested the hypothesis that chronic ethanol consumption disrupts the molecular circadian clock in the liver and potentially changes the diurnal expression patterns of lipid metabolism genes. Consistent with previous studies, male C57BL/6J mice fed an ethanol-containing diet exhibited higher levels of liver triglycerides compared to control mice, indicating hepatic steatosis. Further, the diurnal oscillations of core clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2 and clock-controlled genes (Dbp, Hlf, Nocturnin, Npas2, Rev-erbα, and Tef were altered in livers from ethanol-fed mice. In contrast, ethanol had only minor effects on the expression of core clock genes in the suprachiasmatic nucleus (SCN. These results were confirmed in Per2(Luciferase knock-in mice, in which ethanol induced a phase advance in PER2::LUC bioluminescence oscillations in liver, but not SCN. Further, there was greater variability in the phase of PER2::LUC oscillations in livers from ethanol-fed mice. Ethanol consumption also affected the diurnal oscillations of metabolic genes, including Adh1, Cpt1a, Cyp2e1, Pck1, Pdk4, Ppargc1a, Ppargc1b and Srebp1c, in the livers of C57BL/6J mice. In summary, chronic ethanol consumption alters the function of the circadian clock in liver. Importantly, these results suggest that chronic ethanol consumption, at levels sufficient to

  12. Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats.

    Science.gov (United States)

    Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I

    2016-09-01

    Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. PMID:27154534

  13. Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

    Directory of Open Access Journals (Sweden)

    Paolo eBotta

    2014-02-01

    Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

  14. Protective effects of quercetine on the neuronal injury in frontal cortex after chronic toluene exposure.

    Science.gov (United States)

    Kanter, Mehmet

    2013-08-01

    The aim of this study was designed to evaluate the possible protective effects of quercetine (QE) on the neuronal injury in the frontal cortex after chronic toluene exposure in rats. The rats were randomly allotted into one of the three experimental groups, namely, groups A (control), B (toluene treated) and C (toluene-treated with QE), where each group contains 10 animals. Control group received 1 ml of normal saline solution, and toluene treatment was performed by the inhalation of 3000 ppm toluene in an 8-h/day and 6-day/week order for 12 weeks. The rats in QE-treated group was given QE (15 mg/kg body weight) once a day intraperitoneally for 12 weeks, starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex after chronic toluene exposure in rats by QE treatment have been reported. In this study, the morphology of neurons in the QE treatment group was well protected. Chronic toluene exposure caused severe degenerative changes, shrunken cytoplasm and extensively dark picnotic nuclei in neurons of the frontal cortex. We conclude that QE therapy causes morphologic improvement in neurodegeneration of frontal cortex after chronic toluene exposure in rats. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats. PMID:22252859

  15. Oral Methylphenidate Alleviates the Fine Motor Dysfunction Caused by Chronic Postnatal Manganese Exposure in Adult Rats

    OpenAIRE

    Beaudin, Stéphane A.; Strupp, Barbara J.; Lasley, Stephen M.; Fornal, Casimir A.; Mandal, Shyamali; Smith, Donald R

    2015-01-01

    Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. R...

  16. Sub-chronic exposure to second hand smoke induces airspace leukocyte infiltration and decreases lung elastance

    Directory of Open Access Journals (Sweden)

    John M. Hartney

    2012-07-01

    Full Text Available Exposure to second hand tobacco smoke is associated with the development and/or exacerbation of several different pulmonary diseases in humans. To better understand the possible effects of second hand smoke exposure in humans, we sub-chronically (4 weeks exposed mice to a mixture of mainstream and sidestream tobacco smoke at concentrations similar to second hand smoke exposure in humans. The inflammatory response to smoke exposures was assessed at the end of this time by enumeration of pulmonary leukocyte infiltration together with measurements of lung elastance and pathology. This response was measured in both healthy wild type (C57BL/6 mice as well as mouse mutants deficient in the expression of Arhgef1 (Arhgef1–/– that display constitutive pulmonary inflammation and decreased lung elastance reminiscent of emphysema. The results from this study show that sub-chronic second hand smoke exposure leads to significantly increased numbers of airspace leukocytes in both healthy and mutant animals. While sub-chronic cigarette smoke exposure is not sufficient to induce changes in lung architecture as measured by mean linear intercept, both groups exhibit a significant decrease in lung elastance. Together these data demonstrate that even sub-chronic exposure to second hand smoke is sufficient to induce pulmonary inflammation and decrease lung elastance in both healthy and diseased animals and in the absence of tissue destruction.

  17. Brown adipose tissue. III. Effect of ethanol, nicotine and caffeine exposure.

    Science.gov (United States)

    Sidlo, J; Zaviacic, M; Trutzová, H

    1996-05-01

    Brown adipose tissue is known to be the most important organ for generating heat in non-shivering thermogenesis. Process of thermogenesis and thermoregulation may be affected by many drugs. The paper deals with actual literary data of effect of ethanol, nicotine and caffeine on brown adipose tissue, heat production and its regulation in experimental animals and in human. PMID:9560910

  18. Modelling the effects of ionizing radiation on survival of animal population: acute versus chronic exposure.

    Science.gov (United States)

    Kryshev, A I; Sazykina, T G

    2015-03-01

    The objective of the present paper was application of a model, which was originally developed to simulate chronic ionizing radiation effects in a generic isolated population, to the case of acute exposure, and comparison of the dynamic features of radiation effects on the population survival in cases of acute and chronic exposure. Two modes of exposure were considered: acute exposure (2-35 Gy) and chronic lifetime exposure with the same integrated dose. Calculations were made for a generic mice population; however, the model can be applied for other animals with proper selection of parameter values. In case of acute exposure, in the range 2-11 Gy, the population response was in two phases. During a first phase, there was a depletion in population survival; the second phase was a recovery period due to reparation of damage and biosynthesis of new biomass. Model predictions indicate that a generic mice population, living in ideal conditions, has the potential for recovery (within a mouse lifetime period) from acute exposure with dose up to 10-11 Gy, i.e., the population may recover from doses above an LD50 (6.2 Gy). Following acute doses above 14 Gy, however, the mice population went to extinction without recovery. In contrast, under chronic lifetime exposures (500 days), radiation had little effect on population survival up to integrated doses of 14-15 Gy, so the survival of a population subjected to chronic exposure was much better compared with that after an acute exposure with the same dose. Due to the effect of "wasted radiation", the integrated dose of chronic exposure could be about two times higher than acute dose, producing the same effect on survival. It is concluded that the developed generic population model including the repair of radiation damage can be applied both to acute and chronic modes of exposure; results of calculations for generic mice population are in qualitative agreement with published data on radiation effects in mice. PMID

  19. Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.

    Science.gov (United States)

    Locker, Alicia R; Marks, Michael J; Kamens, Helen M; Klein, Laura Cousino

    2016-05-01

    Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol consumption is also common during adolescence. Past studies report that nicotine and ethanol activate dopamine neurons in the reward pathway and may increase synaptic levels of dopamine in the nucleus accumbens through nicotinic acetylcholine receptor (nAChR) stimulation. Activation of the reward pathway during adolescence through drug use may produce neural alterations affecting subsequent drug consumption. Consequently, the effect of nicotine exposure on binge alcohol consumption was examined along with an assessment of the neurobiological underpinnings that drive adolescent use of these drugs. Adolescent C57BL/6J mice (postnatal days 35-44) were exposed to either water or nicotine (200μg/ml) for ten days. On the final four days, ethanol intake was examined using the drinking-in-the-dark paradigm. Nicotine-exposed mice consumed significantly more ethanol and displayed higher blood ethanol concentrations than did control mice. Autoradiographic analysis of nAChR density revealed higher epibatidine binding in frontal cortical regions in mice exposed to nicotine and ethanol compared to mice exposed to ethanol only. These data show that nicotine exposure during adolescence increases subsequent binge ethanol consumption, and may affect the number of nAChRs in regions of the brain reward pathway, specifically the frontal cortex. PMID:26428091

  20. In Vivo Zonal Variation and Liver Cell-Type Specific NF-κB Localization after Chronic Adaptation to Ethanol and following Partial Hepatectomy.

    Directory of Open Access Journals (Sweden)

    Harshavardhan Nilakantan

    Full Text Available NF-κB is a major inflammatory response mediator in the liver, playing a key role in the pathogenesis of alcoholic liver injury. We investigated zonal as well as liver cell type-specific distribution of NF-κB activation across the liver acinus following adaptation to chronic ethanol intake and 70% partial hepatectomy (PHx. We employed immunofluorescence staining, digital image analysis and statistical distributional analysis to quantify subcellular localization of NF-κB in hepatocytes and hepatic stellate cells (HSCs. We detected significant spatial heterogeneity of NF-κB expression and cellular localization between cytoplasm and nucleus across liver tissue. Our main aims involved investigating the zonal bias in NF-κB localization and determining to what extent chronic ethanol intake affects this zonal bias with in hepatocytes at baseline and post-PHx. Hepatocytes in the periportal area showed higher NF-κB expression than in the pericentral region in the carbohydrate-fed controls, but not in the ethanol group. However, the distribution of NF-κB nuclear localization in hepatocytes was shifted towards higher levels in pericentral region than in periportal area, across all treatment conditions. Chronic ethanol intake shifted the NF-κB distribution towards higher nuclear fraction in hepatocytes as compared to the pair-fed control group. Ethanol also stimulated higher NF-κB expression in a subpopulation of HSCs. In the control group, PHx elicited a shift towards higher NF-κB nuclear fraction in hepatocytes. However, this distribution remained unchanged in the ethanol group post-PHx. HSCs showed a lower NF-κB expression following PHx in both ethanol and control groups. We conclude that adaptation to chronic ethanol intake attenuates the liver zonal variation in NF-κB expression and limits the PHx-induced NF-κB activation in hepatocytes, but does not alter the NF-κB expression changes in HSCs in response to PHx. Our findings provide new

  1. Impacts of chronic low-level nicotine exposure on Caenorhabditis elegans reproduction: Identification of novel gene targets

    OpenAIRE

    Michael A Smith; Zhang, Yanqiong; Polli, Joseph R.; Wu, Hongmei; Zhang, Baohong; Xiao, Peng; Farwell, Mary A.; Pan, Xiaoping

    2013-01-01

    Effects and mechanisms of chronic exposure to low levels of nicotine is an area fundamentally important however less investigated. We employed the model organism Caenorhabditis elegans to investigate potential impacts of chronic (24 h) and low nicotine exposure (6.17–194.5 μM) on stimulus-response, reproduction, and gene expressions. Nicotine significantly affects the organism's response to touch stimulus (p = 0.031), which follows a dose-dependent pattern. Chronic nicotine exposure promotes ...

  2. Acute exposure to ethanol on gestational day 15 affects social motivation of female offspring

    OpenAIRE

    Varlinskaya, Elena I.; Mooney, Sandra M.

    2013-01-01

    Alterations in social behavior are a hallmark of many neurodevelopmental disorders in humans. In rodents, social behavior is affected by prenatal insults. The outcomes are dependent on the timing of the insult as well as the sex and age of the animal tested. The limbic system is particularly important for social behavior, and a peak of neurogenesis within this system occurs on gestational day (G)15. Neurons appear particularly vulnerable to ethanol insult around the time they become post-mito...

  3. 38 CFR 3.316 - Claims based on chronic effects of exposure to mustard gas and Lewisite.

    Science.gov (United States)

    2010-07-01

    ..., bronchitis, emphysema, asthma or chronic obstructive pulmonary disease. (3) Full-body exposure to nitrogen mustard during active military service together with the subsequent development of acute...

  4. Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits.

    Science.gov (United States)

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Ellis, Jonathan D; Walters, Elliot T; Stout, Kristen A; McIntosh, J Michael; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2015-12-01

    Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [(125)I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [(125)I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection. PMID:26391161

  5. Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Sean H Ling

    2009-06-01

    Full Text Available Sean H Ling, Stephan F van EedenJames Hogg iCAPTURE Centre for Pulmonary and Cardiovascular Research and Heart and Lung Institute, University of British Columbia, Vancouver, British Columbia, CanadaAbstract: Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary. Strong epidemiological evidence suggests that exposure to particulate matter (PM air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD resulting in increased morbidity and mortality. However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD. The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces. Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease. This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD.Keywords: chronic obstructive pulmonary disease, particulate matter, air pollution, alveolar macrophage

  6. Influence of chronic x-ray exposure on adrenal glucocorticoid function and adrenocorticocyte membrane potential

    International Nuclear Information System (INIS)

    The peculiarities of adrenal glucocorticoid function and membrane potential (MP) of zona fasciculata adrenocorticocyte (ACC) in rats after chronic x-ray exposure was studied. The changes of adrenal glucocorticoid function caused by chronic x-ray exposure within a relatively small period of irradiation (1.5 months) are obscure and manifest themselves only at physiological load. With the prolongation of the period (8 and 15 months), more considerable inhibition of the adrenal glucocorticoid function and disturbances in the membrane mechanisms of ACC MP level regulation are revealed

  7. Cytogenetic studies in workers with chronic occupational radiation exposure

    International Nuclear Information System (INIS)

    The technique of chromosomal aberration detection on peripheral lymphocytes blood samples from monazite industry workers was used to study the cytogenetic effect of low chronic radiation doses. Cells from 51 workers and 21 controls were analysed. Cytogenetic data from individuals from different working areas were statistically compared among themselves and with the control group. The possible correlations between chromosomal aberration frequencies and cumulative external dose and working time were investigated. The influence of smoking was also tested. The link to the wives spontaneous abortions was analysed. Our results indicate possible biological effects on this sample of workers. (author)

  8. Exposure to regular gasoline and ethanol oxyfuel during refueling in Alaska.

    OpenAIRE

    Backer, L.C.; Egeland, G. M.; Ashley, D L; Lawryk, N J; Weisel, C P; White, M C; Bundy, T; Shortt, E; Middaugh, J P

    1997-01-01

    Although most people are thought to receive their highest acute exposures to gasoline while refueling, relatively little is actually known about personal, nonoccupational exposures to gasoline during refueling activities. This study was designed to measure exposures associated with the use of an oxygenated fuel under cold conditions in Fairbanks, Alaska. We compared concentrations of gasoline components in the blood and in the personal breathing zone (PBZ) of people who pumped regular unleade...

  9. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M;

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in...... female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of...

  10. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    Science.gov (United States)

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-01-01

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother. PMID:27399225

  11. Impairment induced by chronic occupational cadmium exposure during brazing process

    International Nuclear Information System (INIS)

    Cadmium (CD) is considered a metal of the 20th century to which all inhabitants of develop societies are exposed. Long-term occupational and environmental exposure to CD often results in renal dysfunction as the kidney is considered the critical target organ. The aim of this work was to evalutate both resporatory and renal manifestations induced by occupational exposure to CD compounds during brazing process, and suggesting a protocol for prevention and control for CD- induced health effects. This study was conducted on 20 males occupationally exposed workers. They are divided into two groups: Group-1 included (10) exposed smokers and group-2 included (10) exposed non-smokers. Results of both groups were compared with those of 10 healthy age and sex matched non-smokers. All subjects were subjected to detailed history taking and laboratory investigations including blood and urinary CD, liver profile (SGOT, SGPT and alkline phosphates), kindey function tests (blood urea, creatinine and urinary beta2- microglobulin). The level of Cd in the atmosphere of the work plase air was also assessed to detect the degree of exposure as it was about 6 times greater than thesave level (1 mu /m3).(1) This study demonstrated elevation levels of blood CD, urea, creatinine and urinary CD and beta2 -microglobulin for both exposed worker groups than the controls. In additions no appreciable were noted for liver function tests, although the levels fell within normal range

  12. Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study

    DEFF Research Database (Denmark)

    Andersen, Zorana J; Hvidberg, Martin; Jensen, Steen S; Ketzel, Matthias; Loft, Steffen; Sørensen, Mette; Tjønneland, Anne; Overvad, Kim; Raaschou-Nielsen, Ole

    2011-01-01

    Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood.......Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood....

  13. Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy

    OpenAIRE

    Ismahil, Mohamed Ameen; Hamid, Tariq; Haberzettl, Petra; Gu, Yan; Chandrasekar, Bysani; Srivastava, Sanjay; Bhatnagar, Aruni; Prabhu, Sumanth D.

    2011-01-01

    Environmental triggers of dilated cardiomyopathy are poorly understood. Acute exposure to acrolein, a ubiquitous aldehyde pollutant, impairs cardiac function and cardioprotective responses in mice. Here, we tested the hypothesis that chronic oral exposure to acrolein induces inflammation and cardiomyopathy. C57BL/6 mice were gavage-fed acrolein (1 mg/kg) or water (vehicle) daily for 48 days. The dose was chosen based on estimates of human daily unsaturated aldehyde consumption. Compared with ...

  14. Acute and chronic ethanol consumption differentially impact pathways limiting hepatic protein synthesis

    OpenAIRE

    Karinch, Anne M.; Martin, Jonathan H.; Vary, Thomas C.

    2008-01-01

    This review identifies the various pathways responsible for modulating hepatic protein synthesis following acute and chronic alcohol intoxication and describes the mechanism(s) responsible for these changes. Alcohol intoxication induces a defect in global protein synthetic rates that is localized to impaired translation of mRNA at the level of peptide-chain initiation. Translation initiation is regulated at two steps: formation of the 43S preinitiation complex [controlled by eukaryotic initia...

  15. Folic acid supplementation reduces oxidative stress and hepatic toxicity in rats treated chronically with ethanol

    OpenAIRE

    Lee, Soo-Jung; Kang, Myung-Hee; Min, Hyesun

    2011-01-01

    Folate deficiency and hyperhomocysteinemia are found in most patients with alcoholic liver disease. Oxidative stress is one of the most important mechanisms contributing to homocysteine (Hcy)-induced tissue injury. However it has not been examined whether exogenous administration of folic acid attenuates oxidative stress and hepatic toxicity. The aim of this study was to investigate the in vivo effect of folic acid supplementation on oxidative stress and hepatic toxicity induced by chronic et...

  16. Controlled exposure of volunteers with chronic obstructive pulmonary disease to sulfur dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Linn, W.S.; Fischer, D.A.; Shamoo, D.A.; Spier, C.E.; Valencia, L.M.; Anzar, U.T.; Hackney, J.D.

    1985-08-01

    Twenty-four volunteers with chronic obstructive pulmonary disease (COPD) were exposed to sulfur dioxide (SO/sub 2/) at 0, 0.4, and 0.8 ppm in an environmental control chamber. Exposures lasted 1 hr and included two 15-min exercise periods (mean exercise ventilation rate 18 liter/min). Pulmonary mechanical function was evaluated before exposures, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry before exposure and during the second exercise period. Symptoms were recorded throughout exposure periods and for 1 week afterward. No statistically significant changes in physiology or symptoms could be attributed to SO/sub 2/ exposure. Older adults with COPD seem less reactive to a given concentration of SO/sub 2/ than heavily exercising young adult asthmatics. This may be due to lower ventilation rates (i.e., lower SO/sub 2/ dose rates) and/or to lower airway reactivity in the COPD group.

  17. Induction of vascular remodeling in the lung by chronic house dust mite exposure.

    Science.gov (United States)

    Rydell-Törmänen, Kristina; Johnson, Jill R; Fattouh, Ramzi; Jordana, Manel; Erjefält, Jonas S

    2008-07-01

    Structural changes to the lung are associated with chronic asthma. In addition to alterations to the airway wall, asthma is associated with vascular modifications, although this aspect of remodeling is poorly understood. We sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. Because many ovalbumin-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we used a protocol of chronic respiratory exposure to house dust mite extract (HDME), which has been shown to induce persistent airway inflammation consistent with that seen in humans with asthma. Mice were exposed to HDME intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks after the end of a 7-week exposure protocol. Measures of vascular remodeling, including total collagen deposition, procollagen I production, endothelial and smooth muscle cell proliferation, smooth muscle area, and presence of myofibroblasts, were investigated histologically in lung vessels of different sizes and locations. We observed an increase in total collagen content, which did not resolve upon cessation of allergen exposure. Other parameters were significantly increased after 7 and/or 20 weeks of allergen exposure but returned to baseline after allergen withdrawal. We conclude that respiratory HDME exposure induces airway remodeling and pulmonary vascular remodeling, and, in accordance with airway remodeling, some components of these structural changes may be irreversible. PMID:18314535

  18. Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Balmes John

    2005-05-01

    Full Text Available Abstract Background Exposure to environmental tobacco smoke (ETS, which contains potent respiratory irritants, may lead to chronic airway inflammation and obstruction. Although ETS exposure appears to cause asthma in children and adults, its role in causing COPD has received limited attention in epidemiologic studies. Methods Using data from a population-based sample of 2,113 U.S. adults aged 55 to 75 years, we examined the association between lifetime ETS exposure and the risk of developing COPD. Participants were recruited from all 48 contiguous U.S. states by random digit dialing. Lifetime ETS exposure was ascertained by structured telephone interview. We used a standard epidemiologic approach to define COPD based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD. Results Higher cumulative lifetime home and work exposure were associated with a greater risk of COPD. The highest quartile of lifetime home ETS exposure was associated with a greater risk of COPD, controlling for age, sex, race, personal smoking history, educational attainment, marital status, and occupational exposure to vapors, gas, dusts, or fumes during the longest held job (OR 1.55; 95% CI 1.09 to 2.21. The highest quartile of lifetime workplace ETS exposure was also related to a greater risk of COPD (OR 1.36; 95% CI 1.002 to 1.84. The population attributable fraction was 11% for the highest quartile of home ETS exposure and 7% for work exposure. Conclusion ETS exposure may be an important cause of COPD. Consequently, public policies aimed at preventing public smoking may reduce the burden of COPD-related death and disability, both by reducing direct smoking and ETS exposure.

  19. Lithium-mediated protection against ethanol neurotoxicity

    Directory of Open Access Journals (Sweden)

    JiaLuo

    2010-06-01

    Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

  20. Graded exposure for chronic low back pain in older adults : a pilot study

    NARCIS (Netherlands)

    Leonhardt, Corinna; Kuss, Katrin; Becker, Annette; Basler, Heinz-Dieter; de jong, Jeroen; Flatau, Brigitta; Laekeman, Marjan; Mattenklodt, Peter; Schuler, Matthias; Vlaeyen, Johan; Quint, Sabine

    2016-01-01

    BACKGROUND AND PURPOSE: Fear-avoidance beliefs in older adults with chronic low back pain (CLBP) can lead to disability. Graded exposure-based active physical therapy could be an option to enhance physical ability in older patients with CLBP. The purpose of this study was to develop a standardized g

  1. Lung functions at school age and chronic exposure to outdoor and indoor air pollution

    Energy Technology Data Exchange (ETDEWEB)

    Neuberger, M.; Kundi, M.; Wiesenberger, W. [Vienna Univ. (Austria). Dept. of Preventive Medicine

    1995-12-31

    Early signs of lung function impairment have been found correlated with annual concentrations of outdoor air pollutants and with passive smoking. To investigate the combined effects of both indicators of chronic exposure to air pollution pulmonary functions in all elementary and high school children of an Austrian town was examined for 5 years. (author)

  2. THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

    Science.gov (United States)

    Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

  3. Prolonged Exposure Treatment of Chronic PTSD in Juvenile Sex Offenders: Promising Results from Two Case Studies

    Science.gov (United States)

    Hunter, John A.

    2010-01-01

    Prolonged exposure (PE) was used to treat chronic PTSD secondary to severe developmental trauma in two adolescent male sex offenders referred for residential sex offender treatment. Both youth were treatment resistant prior to initiation of PE and showed evidence of long-standing irritability and depression/anxiety. Clinical observation and…

  4. SOME EFFECTS OF CHRONIC TRITIUM EXPOSURE DURING SELECTED AGES IN THE RAT

    Science.gov (United States)

    To assess the implication of age at the time of exposure to chronic irradiation, rats were exposed to constant tritium (HTO) activities of 10 microcuries/ml of body water for 42 days beginning either on the first day of pregnancy or at birth, or at 42 days or 74 days of age. This...

  5. RESPONSES OF SUBJECTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AFTER EXPOSURES TO 0.3 PPM OZONE

    Science.gov (United States)

    The authors previously reported (1982) that the respiratory mechanics of intermittently exercising persons with chronic obstructive pulmonary disease (COPD) were unaffected by a 2-h exposure to 0.2 ppm ozone. Employing a single-blind cross-over design protocol, 13 white men with ...

  6. Effects of a Chronic Lower Range of Triclosan Exposure on a Stream Mesocosm Community

    Science.gov (United States)

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is an antimicrobial found in consumer soaps and toothpaste. It is in treated wastewater effluents at low part per billion concentrations, representing a potentially chronic exposure condition for biota inhabiting receiving strea...

  7. Inequitable Chronic Lead Exposure: A Dual Legacy of Social and Environmental Injustice.

    Science.gov (United States)

    Leech, Tamara G J; Adams, Elizabeth A; Weathers, Tess D; Staten, Lisa K; Filippelli, Gabriel M

    2016-01-01

    Both historic and contemporary factors contribute to the current unequal distribution of lead in urban environments and the disproportionate impact lead exposure has on the health and well-being of low-income minority communities. We consider the enduring impact of lead through the lens of environmental justice, taking into account well-documented geographic concentrations of lead, legacy sources that produce chronic exposures, and intergenerational transfers of risk. We discuss the most promising type of public health action to address inequitable lead exposure and uptake: primordial prevention efforts that address the most fundamental causes of diseases by intervening in structural and systemic inequalities. PMID:27214670

  8. Effects of different exercise protocols on ethanol-induced spatial memory impairment in adult male rats.

    Science.gov (United States)

    Hashemi Nosrat Abadi, T; Vaghef, L; Babri, S; Mahmood-Alilo, M; Beirami, M

    2013-06-01

    Chronic ethanol consumption is often accompanied by numerous cognitive deficits and may lead to long-lasting impairments in spatial learning and memory. The aim of the present study was to evaluate the therapeutic potential of regular treadmill exercise on hippocampal-dependent memory in ethanol-treated rats. Spatial memory was tested in a Morris Water Maze task. Adult male Wistar rats were exposed to ethanol (4 g/kg, 20% v/v for 4 weeks) and effects of three exercise protocols (pre-ethanol, post-ethanol and pre-to-post-ethanol treatment) were examined. Results showed that ethanol exposure resulted in longer escape latencies during the acquisition phase of the Morris Water Maze task. Moreover, all three exercise protocols significantly decreased the latency to locate the hidden platform. During the probe trial, ethanol led to decreased time spent in the target quadrant. In contrast, performance on the probe trial was significantly better in the rats that had done the post- and pre-to-post-ethanol, but not pre-ethanol, exercises. These findings suggest that treadmill running can attenuate the adverse effects of chronic ethanol exposure on spatial memory, and may serve as a non-pharmacological alcohol abuse treatment. PMID:23683528

  9. Effects of acute and chronic ethanol exposure on the behavior of adult zebrafish (Danio rerio)

    OpenAIRE

    Gerlai, Robert; Lee, Vallent; Blaser, Rachel

    2006-01-01

    The zebrafish has been a popular subject of embryology and genetic research for the past three decades. Recently, however, the interest in its neurobiology and behavior has also increased. Nevertheless, compared to other model organisms, e.g., rodents, zebrafish behavior is understudied and very few behavioral paradigms exist for mutation or drug screening purposes. Alcoholism is one of the biggest and costliest diseases whose mechanisms are not well understood. Model organisms such as the ze...

  10. MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells.

    Science.gov (United States)

    Tsai, Pai-Chi; Bake, Shameena; Balaraman, Sridevi; Rawlings, Jeremy; Holgate, Rhonda R; Dubois, Dustin; Miranda, Rajesh C

    2014-01-01

    Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3'UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development. PMID:25063196

  11. MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

    Directory of Open Access Journals (Sweden)

    Pai-Chi Tsai

    2014-07-01

    Full Text Available Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.

  12. Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol

    OpenAIRE

    Suryanarayanan, A.; Carter, JM; Landin, JD; Morrow, AL; Werner, DF; Spigelman, I

    2016-01-01

    Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic E...

  13. No effect of low-level chronic neonicotinoid exposure on bumblebee learning and fecundity.

    Science.gov (United States)

    Piiroinen, Saija; Botías, Cristina; Nicholls, Elizabeth; Goulson, Dave

    2016-01-01

    In recent years, many pollinators have declined in abundance and diversity worldwide, presenting a potential threat to agricultural productivity, biodiversity and the functioning of natural ecosystems. One of the most debated factors proposed to be contributing to pollinator declines is exposure to pesticides, particularly neonicotinoids, a widely used class of systemic insecticide. Also, newly emerging parasites and diseases, thought to be spread via contact with managed honeybees, may pose threats to other pollinators such as bumblebees. Compared to honeybees, bumblebees could be particularly vulnerable to the effects of stressors due to their smaller and more short-lived colonies. Here, we studied the effect of field-realistic, chronic clothianidin exposure and inoculation with the parasite Nosema ceranae on survival, fecundity, sugar water collection and learning using queenless Bombus terrestris audax microcolonies in the laboratory. Chronic exposure to 1 ppb clothianidin had no significant effects on the traits studied. Interestingly, pesticide exposure in combination with additional stress caused by harnessing bees for Proboscis Extension Response (PER) learning assays, led to an increase in mortality. In contrast to previous findings, the bees did not become infected by N. ceranae after experimental inoculation with the parasite spores, suggesting variability in host resistance or parasite virulence. However, this treatment induced a slight, short-term reduction in sugar water collection, potentially through stimulation of the immune system of the bees. Our results suggest that chronic exposure to 1 ppb clothianidin does not have adverse effects on bumblebee fecundity or learning ability. PMID:27014515

  14. Ethanol exposure interacts with training conditions to influence behavioral adaptation to a negative instrumental contingency

    Directory of Open Access Journals (Sweden)

    Regina A. Mangieri

    2014-06-01

    Full Text Available We previously reported that, in male, Long Evans rats, instrumental lever pressing that had been reinforced during limited training under a variable interval (VI schedule by oral self-administration of a 10% sucrose/10% ethanol (10S10E solution was insensitive to devaluation of 10S10E. In contrast, lever pressing that had been reinforced under a variable ratio (VR schedule, or by self-administration of 10% sucrose (10S alone, was sensitive to outcome devaluation. The relative insensitivity to outcome devaluation indicated that seeking of 10S10E by the VI-trained rats had become an instrumental habit. In the present study we employed an alternative operational definition of an instrumental habit and compared the effect of reversing the action-outcome contingency on lever press performance by rats trained under the same experimental conditions. Male Long Evans rats received daily operant training, in which lever presses were reinforced by 10S10E or 10S, under VI or VR schedules. After nine sessions of VI or VR training, rats were tested over four sessions in which the instrumental contingency was changed so that a lever press would prevent reinforcer delivery for 120 seconds. We found that rats that had been trained to lever press for 10S10E under the VR schedule showed a greater change in lever pressing across testing sessions than those that had received 10S10E reinforcement under the VI schedule. There was no such interaction with reinforcement schedule for rats that had received only 10S reinforcement during training. These findings are consistent with those of our previous study, and provide further evidence that addition of ethanol to sucrose may promote habitual responding in an instrumental task.

  15. Effects of prenatal and postnatal maternal ethanol on offspring response to alcohol and psychostimulants in long evans rats.

    Science.gov (United States)

    Barbier, E; Houchi, H; Warnault, V; Pierrefiche, O; Daoust, M; Naassila, M

    2009-06-30

    An important factor that may influence addiction liability is exposure during the early life period. Exposure to ethanol, early in life, can have long-lasting implications on brain function and drugs of abuse response later in life. In the present study we investigated the behavioral responses to ethanol and to psychostimulants in Long Evans rats that have been exposed to pre- and postnatal ethanol. Since a relationship between heightened drug intake and susceptibility to drug-induced locomotor activity/sensitization has been demonstrated, we tested these behavioral responses, in control and early life ethanol-exposed animals. The young adult male and female progeny were tested for locomotor response to alcohol, cocaine and d-amphetamine. Sedative, rewarding effects of alcohol and alcohol consumption were measured. Our results show that early life ethanol exposure behaviorally sensitized animals to subsequent ethanol and psychostimulants exposure. Ethanol-exposed animals were also more sensitive to the hyperlocomotor effects of all drugs of abuse tested and to those of the dopamine receptor agonist apomorphine. Locomotor sensitization to repeated injections of cocaine was facilitated in ethanol-exposed animals. Ethanol-induced conditioned place preference was also facilitated in ethanol-exposed animals. Ethanol consumption and preference were increased after early life ethanol exposure and this was associated with decreased sensitivity to the sedative effects of ethanol. The altered behavioral responses to drugs of abuse were associated with decreased striatal dopamine transporter and hippocampal NMDAR binding. Our results outline an increased vulnerability to rewarding and stimulant effects of ethanol and psychostimulants and support the epidemiological and clinical data that suggested that early chronic exposure to ethanol may increase the propensity for later self-administration of ethanol or other substances. PMID:19348874

  16. Antihyperglycemic Effect on Chronic Administration of Butanol Fraction of Ethanol Extract of Moringa Stenopetala Leaves in Alloxan Induced Diabetic Mice

    Institute of Scientific and Technical Information of China (English)

    Alemayehu Toma; Eyasu Makonnen; Asfaw Debella; Birhanu Tesfaye

    2012-01-01

    Objective: The present study was conducted to evaluate the antihyperglycemic activity on chronic administration of the butanol fraction of the ethanol extract of Moringa Stenopetala leaves in alloxan induced diabetic mice. Methods: The mice were grouped in four groups; Normal control, Diabetic control, Butanol fraction treated and standard drug treated groups. The Diabetic mice received the butanol fraction of Moringa stenopetala daily for 28 days. Results: The butanol fraction of Moringastenopetala treatment resulted in significant reduction of fasting blood glucose level, serum total cholesterol and triglycerides level. This fraction also showed a tendency to improve body weight gain in diabetic mice. Its oral LD50 was found to be greater than 5000mg/Kg indicating its safety in mice. Conclusions: Though the mechanism of action of Moringa stenopetala seems to be similar to that of sulfonylureas, further studies should be done to confirm its mechanism of antidiabetic action. Furthermore the active principle(s) responsible for the antidabetic effects should also be identified.

  17. Characterisation of cochlear inflammation in mice following acute and chronic noise exposure.

    Science.gov (United States)

    Tan, Winston J T; Thorne, Peter R; Vlajkovic, Srdjan M

    2016-08-01

    Oxidative stress has been established as the key mechanism of the cochlear damage underlying noise-induced hearing loss, however, emerging evidence suggests that cochlear inflammation may also be a major contributor. This study aimed to improve our understanding of the cochlear inflammatory response associated with acute and chronic noise exposure. C57BL/6 mice were exposed to acute traumatic noise (100 dBSPL, 8-16 kHz for 24 h) and their cochleae collected at various intervals thereafter, up to 7 days. Using quantitative RT-PCR and immunohistochemistry, changes in expression levels of proinflammatory cytokines (TNF-α, IL-1β), chemokines (CCL2) and cell adhesion molecules (ICAM-1) were studied. All gene transcripts displayed similar dynamics of expression, with an early upregulation at 6 h post-exposure, followed by a second peak at 7 days. ICAM-1 immunoexpression increased significantly in the inferior region of the spiral ligament, peaking 24 h post-exposure. The early expression of proinflammatory mediators likely mediates the recruitment and extravasation of inflammatory cells into the noise-exposed cochlea. The occurrence of the latter expression peak is not clear, but it may be associated with reparative processes initiated in response to cochlear damage. Chronic exposure to moderate noise (90 dBSPL, 8-16 kHz, 2 h/day, up to 4 weeks) also elicited an inflammatory response, reaching a maximum after 2 weeks, suggesting that cochlear damage and hearing loss associated with chronic environmental noise exposure may be linked to inflammatory processes in the cochlea. This study thus provides further insight into the dynamics of the cochlear inflammatory response induced by exposure to acute and chronic noise. PMID:27109494

  18. Inflammation mediators in employees in chronic exposure to neurotoxicants

    Directory of Open Access Journals (Sweden)

    Galina Bodienkova

    2014-08-01

    Full Text Available Objectives: The aim of this work is to perform comparative estimation of cytokines levels in chlorinated hydrocarbons and metallic mercury exposure in employees in the dynamics of neurologic disorders formation. Material and Methods: The contents of cytokines IL-1β, IL-2, IL-4, IL-6, TNF-α, INF-γ were determined in blood sera using the method of hardphasic immunoferment analysis. The significance of different average values was assessed using the parametric and non-parametric criteria - Student (in normal distribution and Mann-Whitney tests taking into account the Bonferonni correction (non-difference from normal distribution. Results: It was shown that, a number of inflammation mediators with the dominance, depending on the expositional toxicant and expression of neurological deficiency, take part in the neurointoxication development. Healthy employees show pro-inflammatory responses with different expression degree, which dominate in the immune regulation processes regardless of the expositional factors (metallic mercury vapors and chlorinated hydrocarbons. Conclusions: The production intensity and interconnection between the pro- and anti-inflammatory cytokines may change in the occupational injuries of the nervous system development process. The decrease in the serum concentrations of cytokines along with the increase of clinical manifestation severity may prove dysregulation of the immune system, which promotes maintaining of pathological process and progradient process of neurointoxication. The most obvious is the imbalance of cytokines in the employees exposed to metallic mercury (in all the examined groups that increases neurointoxication in the distant period.

  19. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

  20. Effect of different stressors on voluntary ethanol intake in ethanol-dependent and nondependent C57BL/6J mice.

    Science.gov (United States)

    Lopez, Marcelo F; Anderson, Rachel I; Becker, Howard C

    2016-03-01

    Several animal models have evaluated the effect of stress on voluntary ethanol intake with mixed results. The experiments reported here examined the effects of different stressors on voluntary ethanol consumption in dependent and nondependent adult male C57BL/6J mice. In Experiment 1, restraint, forced swim, and social defeat stress procedures all tended to reduce ethanol intake in nondependent mice regardless of whether the stress experience occurred 1 h or 4 h prior to ethanol access. The reduction in ethanol consumption was most robust following restraint stress. Experiment 2 examined the effects of forced swim stress and social defeat stress on drinking in a dependence model that involved repeated cycles of chronic intermittent ethanol (CIE) exposure. Repeated exposure to forced swim stress prior to intervening test drinking periods that followed repeated cycles of CIE exposure further increased ethanol consumption in CIE-exposed mice while not altering intake in nondependent mice. In contrast, repeated exposure to the social defeat stressor in a similar manner reduced ethanol consumption in CIE-exposed mice while not altering drinking in nondependent mice. Results from Experiment 3 confirmed this selective effect of forced swim stress increasing ethanol consumption in mice with a history of CIE exposure, and also demonstrated that enhanced drinking is only observed when the forced swim stressor is administered during each test drinking week, but not if it is applied only during the final test week. Collectively, these studies point to a unique interaction between repeated stress experience and CIE exposure, and also suggest that such an effect depends on the nature of the stressor. Future studies will need to further explore the generalizability of these results, as well as mechanisms underlying the ability of forced swim stress to selectively further enhance ethanol consumption in dependent (CIE-exposed) mice but not alter intake in nondependent animals

  1. Whey protein concentrate promotes the production of glutathione (GSH) by GSH reductase in the PC12 cell line after acute ethanol exposure.

    Science.gov (United States)

    Tseng, Yang-Ming; Lin, Shu-Kai; Hsiao, Jen-Kuei; Chen, Ing-Jun; Lee, Jang-Hwa; Wu, Szu-Hsien; Tsai, Li-Yu

    2006-04-01

    Excessive ethanol consumption may increase the production of reactive oxygen species (ROS), which results in the damage of tissues, especially the neurons and glial cells in the central nervous system (CNS). The purpose of this study is to evaluate the effects of whey protein concentrate (WPC) on the glutathione (GSH) status after acute ethanol exposure in the pheochromocytoma (PC12) cell line. In this study, we assayed the cell viability, the percentage of lactate dehydrogenase released (% LDH released), the level of GSH, and the activity of GSH reductase (GRx). The results showed that with the supplement of WPC, the cell viability displayed no significant difference after acute exposure of ethanol in groups with or without ethanol treatment. The ethanol-induced cytotoxicity showed a slight decrease ,and the level of GSH showed a significant increase. The activity of GRx significantly increased when 0.1, 10mg/ml of WPC was supplied. In conclusion, these results suggest that WPC in a moderate concentration should be a precursor agent to promote the production of GSH and will enhance the antioxidant capacity in the PC12 cell line. PMID:16360258

  2. Bumblebee learning and memory is impaired by chronic exposure to a neonicotinoid pesticide.

    Science.gov (United States)

    Stanley, Dara A; Smith, Karen E; Raine, Nigel E

    2015-01-01

    Bumblebees are exposed to pesticides applied for crop protection while foraging on treated plants, with increasing evidence suggesting that this sublethal exposure has implications for pollinator declines. The challenges of navigating and learning to manipulate many different flowers underline the critical role learning plays for the foraging success and survival of bees. We assessed the impacts of both acute and chronic exposure to field-realistic levels of a widely applied neonicotinoid insecticide, thiamethoxam, on bumblebee odour learning and memory. Although bees exposed to acute doses showed conditioned responses less frequently than controls, we found no difference in the number of individuals able to learn at field-realistic exposure levels. However, following chronic pesticide exposure, bees exposed to field-realistic levels learnt more slowly and their short-term memory was significantly impaired following exposure to 2.4 ppb pesticide. These results indicate that field-realistic pesticide exposure can have appreciable impacts on learning and memory, with potential implications for essential individual behaviour and colony fitness. PMID:26568480

  3. Heavy metal uranium affects the brain cholinergic system in rat following sub-chronic and chronic exposure

    International Nuclear Information System (INIS)

    Uranium is a heavy metal naturally present in the environment that may be chronically ingested by the population. Previous studies have shown that uranium is present in the brain and alters behaviour, notably locomotor activity, sensorimotor ability, sleep/wake cycle and the memory process, but also metabolism of neurotransmitters. The cholinergic system mediates many cognitive systems, including those disturbed after chronic exposure to uranium i.e., spatial memory, sleep/wake cycle and locomotor activity. The objective of this study was to assess whether these disorders follow uranium-induced alteration of the cholinergic system. In comparison with 40 control rats, 40 rats drank 40 mg/L uranyl nitrate for 1.5 or 9 months. Cortex and hippocampus were removed and gene expression and protein level were analysed to determine potential changes in cholinergic receptors and acetylcholine levels. The expression of genes showed various alterations in the two brain areas after short- and long-term exposure. Nevertheless, protein levels of the choline acetyltransferase enzyme (ChAT), the vesicular transporter of acetylcholine (VAChT) and the nicotinic receptor β2 sub-unit (nAChRβ2) were unmodified in all cases of the experiment and muscarinic receptor type 1 (m1AChR) protein level was disturbed only after 9 months of exposure in the cortex (-30%). Acetylcholine levels were unchanged in the hippocampus after 1.5 and 9 months, but were decreased in the cortex after 1.5 months only (-22%). Acetylcholinesterase (AChE) activity was also unchanged in the hippocampus but decreased in the cortex after 1.5 and 9 months (-16% and -18%, respectively). Taken together, these data indicate that the cholinergic system is a target of uranium exposure in a structure-dependent and time-dependent manner. These cholinergic alterations could participate in behavioural impairments.

  4. Chronic Exposure to Ambient Levels of Urban Particles Affects Mouse Lung Development

    Science.gov (United States)

    Mauad, Thais; Rivero, Dolores Helena Rodriguez Ferreira; de Oliveira, Regiani Carvalho; de Faria Coimbra Lichtenfels, Ana Julia; Guimarães, Eliane Tigre; de Andre, Paulo Afonso; Kasahara, David Itiro; de Siqueira Bueno, Heloisa Maria; Saldiva, Paulo Hilário Nascimento

    2008-01-01

    Rationale: Chronic exposure to air pollution has been associated with adverse effects on children's lung growth. Objectives: We analyzed the effects of chronic exposure to urban levels of particulate matter (PM) on selected phases of mouse lung development. Methods: The exposure occurred in two open-top chambers (filtered and nonfiltered) placed 20 m from a street with heavy traffic in São Paulo, 24 hours/day for 8 months. There was a significant reduction of the levels of PM2.5 inside the filtered chamber (filtered = 2.9 ± 3.0 μg/m3, nonfiltered = 16.8 ± 8.3 μg/m3; P = 0.001). At this exposure site, vehicular sources are the major components of PM2.5 (PM ≤ 2.5μm). Exposure of the parental generation in the two chambers occurred from the 10th to the 120th days of life. After mating and birth of offspring, a crossover of mothers and pups occurred within the chambers, resulting in four groups of pups: nonexposed, prenatal, postnatal, and pre+postnatal. Offspring were killed at the age of 15 (n = 42) and 90 (n = 35) days; lungs were analyzed by morphometry for surface to volume ratio (as an estimator of alveolization). Pressure–volume curves were performed in the older groups, using a 20-ml plethysmograph. Measurements and Main Results: Mice exposed to PM2.5 pre+postnatally presented a smaller surface to volume ratio when compared with nonexposed animals (P = 0.036). The pre+postnatal group presented reduced inspiratory and expiratory volumes at higher levels of transpulmonary pressure (P = 0.001). There were no differences among prenatal and postnatal exposure and nonexposed animals. Conclusions: Our data provide anatomical and functional support to the concept that chronic exposure to urban PM affects lung growth. PMID:18596224

  5. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

    Science.gov (United States)

    Anyanwu, Ebere; Campbell, Andrew W; Jones, Joseph; Ehiri, John E; Akpan, Akpan I

    2003-11-13

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range

  6. The Neurological Significance of Abnormal Natural Killer Cell Activity in Chronic Toxigenic Mold Exposures

    Directory of Open Access Journals (Sweden)

    Ebere Anyanwu

    2003-01-01

    Full Text Available Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40�C (104�F, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide

  7. Comparative sensitivity of three populations of the cladoceran Moinodaphnia macleayi to acute and chronic uranium exposure.

    Science.gov (United States)

    Semaan, M; Holdway, D A; van Dam, R A

    2001-10-01

    Assessment of differences in the response of three different populations of the tropical cladoceran Moinodaphnia macleayi to uranium exposure was evaluated. The populations tested included a laboratory stock (maintained for 10 years), a wild population collected from Bowerbird Billabong (an uncontaminated environment), and a population collected from Djalkmara Billabong (a relatively contaminated environment with elevated levels of uranium), located on the Ranger uranium mine site, Jabiru East, NT, Australia. Chronic and acute toxicity of uranium was determined for all three populations. The no-observed-effect-concentration (NOEC; reproduction) and lowest observed-effect-concentration (LOEC; reproduction) for uranium ranged between 8-31 micrograms L-1 and 20-49 micrograms L-1, respectively, for all three populations. The 48 h EC50 (immobilization-lethality) for uranium ranged between 160-390 micrograms L-1 for all three populations. There was little difference in the response of the three populations of M. macleayi to acute and chronic uranium exposure, although the response of the laboratory population to chronic uranium exposure appeared more variable than the "wild" populations. There was no apparent tolerance in the population of M. macleayi obtained from Djalkmara Billabong when exposed to elevated levels of uranium. M. macleayi was significantly more sensitive to uranium exposure than other species previously tested. It was concluded that the sensitivity of the laboratory population (to uranium) is still representative of natural M. macleayi populations. PMID:11594022

  8. A safe strategy to decrease fetal lead exposure in a woman with chronic intoxication.

    Science.gov (United States)

    Leiba, Adi; Hu, Howard; Zheng, Amin; Kales, Stefanos N

    2010-08-01

    During pregnancy skeletal lead is mobilized by maternal bone turnover and can threaten fetal development. The exact strategy suggested to women of childbearing age, who were chronically exposed to lead, and, thus, have high bone lead burden, is not well established. We describe 4 years of follow-up of a 29-year-old woman with chronic lead intoxication. We (a) advised her to delay conception until 'toxicological clearance', (b) treated her with multiple courses of lead chelator, DMSA, and (c) prescribed oral calcium. Patient had low blood lead and protoporphyrin level during pregnancy until delivery. Delaying conception, lead chelation, and calcium supplementation can decrease fetal exposure. PMID:20459344

  9. Reaction of fresh water zooplankton community to chronic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Osipov, D.; Pryakhin, E. [Urals Research Center for Radiation Medicine - URCRM (Russian Federation); Ivanov, I. [FSUE Mayak PA (Russian Federation)

    2014-07-01

    The characteristic features of ecological community as a whole and cenosis of zooplankton organisms as part of it determine the intensity of the processes of self-purification of water and the formation of a particular body of water. Identifying features of the structure and composition of the zooplankton community of aquatic ecosystems exposed to different levels of radiation exposure, it is necessary to identify patterns of changes in zooplankton and hydro-biocenosis as a whole. Industrial reservoirs, the storage of liquid low-level radioactive waste 'Mayak' for decades, have high radiation load. A large range of levels of radioactive contamination (total volume beta-activity in water varies from 2.2x10{sup 3} to 2.3x10{sup 7} Bq/l, total volume alpha-activity - from 2.6x10{sup -1} to 3.1x10{sup 3} Bq/l) provides a unique opportunity to study ecosystems in a number of reservoirs with increasing impact of radiation factor. We studied five reservoirs that were used as the storage of low-and intermediate-level liquid radioactive waste pond and one comparison water body. In parallel with zooplankton sampling water samples were collected for hydro-chemical analysis. 41 indicators were analysed in order to assess the water chemistry. To determine the content of radionuclides in the various components of the ecosystem samples were collected from water, bottom sediments and plankton. Sampling of zooplankton for the quantitative analysis was performed using the method of weighted average auto bathometer. Apshteyn's plankton net of the surface horizon was used for qualitative analysis of the species composition of zooplankton. Software package ERICA Assessment Tool 2012 was used for the calculation of the absorbed dose rate. Species diversity and biomass of zooplankton, the share of rotifers in the number of species, abundance and biomass decrease with the increase of the absorbed dose rate and salinity. The number of species in a sample decreases with the

  10. A Low Ethanol Dose Affects all Types of Cells in Mixed Long-Term Embryonic Cultures of the Cerebellum

    DEFF Research Database (Denmark)

    Pickering, Chris; Wicher, Grzegorz; Rosendahl, Sofi;

    2010-01-01

    . We exposed a primary culture of rat cerebellum from embryonic day 17 (corresponding to second trimester in humans) to ethanol at a concentration of 17.6 mM which is roughly equivalent to one glass of wine. Acutely, there was no change in cell viability after 5 or 8 days of exposure relative to...... of this ethanol dose, cultures were exposed for 30 days. After this period, virtually no neurons or myelinating oligodendrocytes were present in the ethanol-treated cultures. In conclusion, chronic exposure to ethanol, even at small doses, dramatically and persistently affects normal development....

  11. Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem

    International Nuclear Information System (INIS)

    Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC–MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.

  12. Antioxidant and antihyperlipidemic effect of Solanum nigrum fruit extract on the experimental model against chronic ethanol toxicity

    OpenAIRE

    Vadivel Arulmozhi; Mani Krishnaveni; Kandhan Karthishwaran; Ganesan Dhamodharan; Sankaran Mirunalini

    2010-01-01

    The possible protective effect of Solanum nigrum fruit extract (SNFEt) was investigated for its antioxidant and antihyperlipidemic activity against ethanol-induced toxicity in rats. The experimental animals were intoxicated with 20% ethanol (7.9 g/kg/day) for 30 days via gastric intubation. SNFEt was administered at the dose of 250 mg/kg body weight along with the daily dose of ethanol for 30 days. From the result it was observed that ethanol-induced rats showed a significant elevation in the...

  13. Low-level chronic exposure to tritium: An improved basis for hazard evaluation

    International Nuclear Information System (INIS)

    The possibility that significant biological effects may result from chronic low-level exposure to 3HOH is the main health and environmental concern regarding tritium from nuclear energy operations. Direct data for such exposure are, however, largely still unavailable. Information on chronic irradiation at low levels derives mostly from γ-ray studies, so extrapolations are necesary for tritium. But controversy exists on tritium's relative biological effectiveness (RBE) compared to γ radiation and on the related quality factor (Q) used for radiation protection (recently adjusted downward from 1.7 to 1). A firmer basis for extrapolation is needed. The author has obtained quantitative data for low-level 3HOH and 60Co γ-ray exposures in the intact mammal. Developing mice were exposed to various doses over 33 days; surviving oocytes were then counted in ovaries and compared with controls, providing dose-response curves for both radiations. By comparing these curves, RBE values were determined. The RBE was found to vary inversely with dose, in accord with the theory of dual radiation action. At γ-ray doses of 50 rads, the RBE was 1.6. It increased at lower doses, reaching a value of approximately 3. With short exposures, the RBE was lower, due possibly to differences in microdistribution of 3H. These results demonstrate that conclusions from both high-dose and short-term experiments are likely to underestimate the effects of low-level chronic exposure to 3HOH. Measurement of the systematic variation of tritium's RBE with dose and recognition of the effect of exposure duration provide a more secure basis for hazard evaluation. (author)

  14. Mitochondrial energy metabolism impairment and liver dysfunction following chronic exposure to dichlorvos

    International Nuclear Information System (INIS)

    Although the effects of acute pesticide poisoning are well known but, hardly any data exists regarding the health effects after long-term low-level exposure. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The present study elucidates a possible mechanism by which chronic organophosphate exposure (dichlorvos 6 mg/kg b.wt., s.c. for 12 weeks) causes liver dysfunction. Mitochondria, a primary site of cellular energy generation and oxygen consumption represent a likely target for organophosphate poisoning. Therefore, the objective of the current study was planned with an aim to investigate the effect of chronic dichlorvos exposure on liver mitochondrial electron transport chain (ETC), mitochondrial calcium uptake and its implications on the induction of liver enzymes and liver dysfunction in rodent model. Our results indicated decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I and II activity. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria isolated from dichlorvos (DDVP) treated rat liver. Mitochondrial preparation from DDVP treated rat liver demonstrated significant increase in mitochondrial Ca2+ uptake and increase ROS levels. The alterations in the mitochondrial calcium uptake, mitochondrial electron transfer enzyme activities and increase ROS levels in turn might have caused an increase in liver enzymes (ALT, AST and ALP). The electron micrographs of liver cells depicted morphological changes in mitochondria as well as nucleus following 12 weeks of exposure to DDVP. These studies provide an evidence of impaired mitochondrial bioenergetics which may lead to liver dysfunction after chronic exposure to dichlorvos.

  15. Chronic exposure of juvenile rats to environmental noise impairs hippocampal cell proliferation in adulthood

    Directory of Open Access Journals (Sweden)

    Fernando Jáuregui-Huerta

    2011-01-01

    Full Text Available Increasing evidence indicates that chronic exposure to environmental noise may permanently affect the central nervous system. The aim of this study was to evaluate the long-term effects of early exposure to environmental noise on the hippocampal cell proliferation of the adult male rat. Early-weaned Wistar rats were exposed for 15 days to a rats′ audiogram-fitted adaptation to a noisy environment. Two months later, the rats were injected with the cellular proliferation marker 5΄bromodeoxiuridine (BrdU, and their brains were processed for immunohistochemical analysis. Coronal sections were immunolabeled with anti-BrdU antibodies to identify new-born cells in dentate gyrus (DG, cornu amonis areas CA1 and CA3. In addition, blood samples were obtained to evaluate corticosterone serum levels after noise exposure. All data are expressed as mean΁standard deviation. For mean comparisons between groups, we used the Student t test. We found an increase in corticosterone serum levels after environmental noise exposure. Interestingly, noise-exposed rats showed a long-term reduction of proliferating cells in the hippocampal formation, as compared to controls. These findings indicate that chronic environmental noise exposure at young ages produces persistent non-auditory impairment that modifies cell proliferation in the hippocampal formation.

  16. Environmental Heavy Metal Exposure and Chronic Kidney Disease in the General Population

    OpenAIRE

    Kim, Nam Hee; Hyun, Young Youl; Lee, Kyu-Beck; Chang, Yoosoo; Rhu, Seungho; Oh, Kook-Hwan; Ahn, Curie

    2015-01-01

    Lead (Pb), mercury (Hg), and cadmium (Cd) are common heavy metal toxins and cause toxicological renal effects at high levels, but the relevance of low-level environmental exposures in the general population is controversial. A total of 1,797 adults who participated in the KNHANES (a cross-sectional nationally representative survey in Korea) were examined, and 128 of them (7.1%) had chronic kidney disease (CKD). Our study assessed the association between Pb, Hg, Cd exposure, and CKD. Blood Pb ...

  17. Chronic disease and early exposure to air-borne mixtures. 2. Exposure assessment.

    Science.gov (United States)

    Argo, James

    2007-10-15

    This work is part of a larger study of the impact of early exposure to releases from industry on the etiology of cancer. Releases from all kraft and sulfite mills, coke ovens, oil refineries, copper, nickel, and lead/zinc smelters operating in Canada during the exposure period of 1967-1970 have been determined. All plumes have been expressed in microg BaP eq/d using the RASH methodology. The releases have been divided into process, boiler fuel, dioxin, and SO2 emissions. Combustion sources have been defined with FIREv6.23. Dioxin congenors are expected in all source types when the boiler fuel is heavy fuel oil, wood or wood bark, or coal. All approximately 90 communities examined have an inverted sex ratio. PMID:17993167

  18. Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid/benzodiazepine receptor site interactions.

    Science.gov (United States)

    Roca, D J; Schiller, G D; Farb, D H

    1988-05-01

    Methylxanthines, such as caffeine and theophylline, are adenosine receptor antagonists that exert dramatic effects upon the behavior of vertebrate animals by increasing attentiveness, anxiety, and convulsive activity. Benzodiazepines, such as flunitrazepam, generally exert behavioral effects that are opposite to those of methylxanthines. We report the finding that chronic exposure of embryonic brain neurons to caffeine or theophylline reduces the ability of gamma-aminobutyric acid (GABA) to potentiate the binding of [3H]flunitrazepam to the GABA/benzodiazepine receptor. This theophylline-induced "uncoupling" of GABA- and benzodiazepine-binding site allosteric interactions is blocked by chloroadenosine, an adenosine receptor agonist, indicating that the chronic effects of theophylline are mediated by a site that resembles an adenosine receptor. We speculate that adverse central nervous system effects of long-term exposure to methylxanthines such as in caffeine-containing beverages or theophylline-containing medications may be exerted by a cell-mediated modification of the GABAA receptor. PMID:2835648

  19. Ethanolic extract of Passiflora edulis Sims leaves inhibits protein glycation and restores the oxidative burst in diabetic rat macrophages after Candida albicans exposure

    Directory of Open Access Journals (Sweden)

    Carolina Fernandes Ribas Martins

    2015-12-01

    Full Text Available abstract This study was conducted to evaluate the effects of the ethanolic extract of Passiflora edulis leaves on blood glucose, protein glycation, NADPH oxidase activity and macrophage phagocytic capacity after Candida albicans exposure in diabetic rats. The Passiflora edulis Sims leaves were dried to 40°C, powdered, extracted by maceration in 70% ethanol, evaporated under reduced pressure and lyophilised. The biochemical tests performed were total phenolic content (TP as determined by the Folin-Ciocalteu assay, trapping potential DPPH assay and total iron-reducing potential. Diabetes was induced by alloxan injection. Protein glycation was determined by AGE and fructosamine serum concentrations. Extract-treated diabetic animals demonstrated lower fructosamine concentrations compared with the diabetic group. Our results suggest that ethanolic Passiflora edulis Sims leaf extraction may have beneficial effects on diabetes and may improve glycaemic control in diabetic rats.

  20. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

    Science.gov (United States)

    Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

    2015-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  1. The Consequences of adolescent chronic unpredictable stress exposure on brain and behavior

    OpenAIRE

    Hollis, Fiona; Isgor, Ceylan; Kabbaj, Mohamed

    2013-01-01

    There is increasing evidence for adolescence as a time period vulnerable to environmental perturbations such as stress. What is unclear is the persistent nature of the effects of stress and how specific these effects are to the type of stressor. In this review, we describe the effects of chronic, unpredictable stress (CUS) exposure during adolescence on adult behavior and brain morphology and function in animal models. We provide evidence for adolescence as a critical window for the effects o...

  2. Chronic estradiol exposure induces oxidative stress in the hypothalamus to decrease hypothalamic dopamine and cause hyperprolactinemia

    OpenAIRE

    MohanKumar, Sheba M.J.; Kasturi, Badrinarayanan S.; Shin, Andrew C.; Balasubramanian, Priya; Gilbreath, Ebony T.; Subramanian, Madhan; MohanKumar, Puliyur S

    2010-01-01

    Estrogens are known to cause hyperprolactinemia, most probably by acting on the tuberoinfundibular dopaminergic (TIDA) system of the hypothalamus. Dopamine (DA) produced by TIDA neurons directly inhibits prolactin secretion and, therefore, to stimulate prolactin secretion, estrogens inhibit TIDA neurons to decrease DA production. However, the mechanism by which estrogen produces this effect is not clear. In the present study, we used a paradigm involving chronic exposure to low levels of estr...

  3. Pulmonary function and exercise-associated changes with chronic low-level paraquat exposure

    OpenAIRE

    Schenker, M B; Stoecklin, Maria T; Lee, Kiyoung; Lupercio, Rafael; Zeballos, R. Jorge; Enright, Paul; Hennessy, Tamara E.; Laurel A. Beckett

    2004-01-01

    The present study was undertaken to test the hypothesis that chronic, low-level paraquat exposure causes restrictive lung function with gas transfer impairment. Three hundred thirty-eight Costa Rican farm workers from banana, coffee and palm oil farms completed a questionnaire, spirometry and single-breath carbon monoxide diffusing capacity. Subjects 40 years of age or older, without other medical risk factors, completed maximal cardiopulmonary exercise tests. Most (66.6%) were paraquat hand...

  4. Biochemical Impedance on Intracellular Functions of Vitamin B12 in Chronic Toxigenic Mold Exposures

    OpenAIRE

    Ebere C. Anyanwu; Ijeoma Kanu

    2007-01-01

    A majority of patients with neurological disorders with chronic exposures to toxigenic molds and mycotoxins has vitamin B12 deficiency that is unrelated to dietary insufficiency. Vitamin B12 is a source of coenzymes, and participates in intracellular recycling of methionine, and in methionine synthase reactions. The biochemical processes that lead to B12 depletion and deficiency are not fully understood. This paper examines and assesses various most likely biochemical reasons that could imped...

  5. Comparative transcriptomic responses to chronic cadmium, fluoranthene, and atrazine exposure in Lumbricus rubellus.

    Science.gov (United States)

    Svendsen, C; Owen, J; Kille, P; Wren, J; Jonker, M J; Headley, B A; Morgan, A J; Blaxter, M; Stürzenbaum, S R; Hankard, P K; Lister, L J; Spurgeon, D J

    2008-06-01

    Transcriptional responses of a soil-dwelling organism (the earthworm Lumbricus rubellus) to three chemicals, cadmium (Cd), fluoranthene (FA), and atrazine (AZ), were measured following chronic exposure, with the aim of identifying the nature of any shared transcriptional response. Principal component analysis indicated full or partial separation of control and exposed samples for each compound but not for the composite set of all control and exposed samples. Partial least-squares discriminant analysis allowed separation of the control and exposed samples for each chemical and also for the composite data set, suggesting a common transcriptional response to exposure. Genes identified as changing in expression level (by the least stringent test for significance) following exposure to two chemicals indicated a substantial number of common genes (> 127). The three compound overlapping gene set, however, comprised only 25 genes. We suggest that the low commonality in transcriptional response may be linked to the chronic concentrations (approximately 10% EC50) and chronic duration (28 days) used. Annotations of the three compound overlapping gene set indicated that genes from pathways most often associated with responses to environmental stress, such as heat shock, phase I and II metabolism, antioxidant defense, and cation balance, were not represented. The strongest annotation signature was for genes important in mitochondrial function and energy metabolism. PMID:18589989

  6. Age influence on mice lung tissue response to [i]Aspergillus fumigatus[/i] chronic exposure

    Directory of Open Access Journals (Sweden)

    Marta Kinga Lemieszek

    2015-02-01

    Full Text Available [b]Introduction and objective[/b]. Exposure to conidia of [i]Aspergillus fumigatus[/i] was described as a causative factor of a number of the respiratory system diseases, including asthma, chronic eosinophilic pneumonia, hypersensitivity pneumonitis and bronchopulmonary aspergillosis. The study investigates the effects of the repeated exposure to [i]A. fumigatus[/i] in mice pulmonary compartment. Our work tackles two, so far insufficiently addressed, important aspects of interaction between affected organism and[i] A. fumigatus[/i]: 1 recurrent character of exposure (characteristic for pathomechanism of the abovementioned disease states and 2 impact of aging, potentially important for the differentiation response to an antigen. [b]Materials and methods[/b]. In order to dissect alterations of the immune system involved with both aging and chronic exposure to [i]A. fumigatus[/i], we used 3- and 18-month-old C57BL/6J mice exposed to repeated[i] A. fumigatus[/i] inhalations for 7 and 28 days. Changes in lung tissue were monitored by histological and biochemical evaluation. Concentration of pro- and anti-inflammatory cytokines in lung homogenates was assessed by ELISA tests. [b]Results and conclusions. [/b]Our study demonstrated that chronic inflammation in pulmonary compartment, characterized by the significant increase of proinflammatory cytokines (IL1, IL6, IL10 levels, was the dominant feature of mice response to repeated [i]A. fumigatus[/i] inhalations. The pattern of cytokines’ profile in the course of exposure was similar in both age groups, however in old mice the growth of the cytokines’ levels was more pronounced (especially in case of IL1.

  7. Role of oxidative stress in liver and kidney in uranium toxicity after chronic exposure

    International Nuclear Information System (INIS)

    Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 μg.g-1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration. (author)

  8. Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat offspring by programming a low-functioning IGF-1 signaling pathway

    Science.gov (United States)

    Ni, Qubo; Tan, Yang; Zhang, Xianrong; Luo, Hanwen; Deng, Yu; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-10-01

    Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol exposure (PEE) are both associated with low birth weight but possible causal interrelationships have not been investigated. To investigate the effects of PEE on the susceptibility to OA in adult rats that experienced intrauterine growth retardation (IUGR), and to explore potential intrauterine mechanisms, we established the rat model of IUGR by PEE and dexamethasone, and the female fetus and 24-week-old adult offspring subjected to strenuous running for 6 weeks were sacrificed. Knee joints were collected from fetuses and adult offspring for histochemistry, immunohistochemistry and qPCR assays. Histological analyses and the Mankin score revealed increased cartilage destruction and accelerated OA progression in adult offspring from the PEE group compared to the control group. Immunohistochemistry showed reduced expression of insulin-like growth factor-1 (IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group experienced IUGR but exhibited a higher postnatal growth rate. The expression of many IGF-1 signaling components was downregulated, which coincided with reduced amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE group. These results suggest that PEE enhances the susceptibility to OA in female adult rat offspring by down-regulating IGF-1 signaling and retarding articular cartilage development.

  9. Does chronic occupational exposure to volatile anesthetic agents influence the rate of neutrophil apoptosis?

    LENUS (Irish Health Repository)

    Goto, Y

    2012-02-03

    PURPOSE: The purpose of this preliminary investigation was to determine whether the rate of neutrophil apoptosis in health care workers is influenced by exposure to volatile anesthetic agents. METHODS: Percentage neutrophil apoptosis (Annexin-V FITC assay) was measured in health care workers (n = 20) and unexposed volunteers (n = 10). For the health care workers, time weighted personal exposure monitoring to N2O, sevoflurane and isoflurane was carried out. RESULTS: The sevoflurane and isoflurane concentrations to which health care workers were exposed were less than recommended levels in all 20 cases. Percent apoptosis was less at 24 (but not at one and 12) hr culture in health care workers [50.5 (9.7)%; P = 0.008] than in unexposed volunteers [57.3 (5.1)%]. CONCLUSION: Inhibition of neutrophil apoptosis at 24 hr culture was demonstrated in health care workers chronically exposed to volatile anesthetic agents. Exposure was well below recommended levels in the both scavenged and unscavenged work areas in which the study was carried out. Further study is required to assess the effect of greater degrees of chronic exposure to volatile anesthetic agents on neutrophil apoptosis.

  10. Chronic effects of maternal ethanol and low-protein intake on growth and blood measurements of beagle pups

    International Nuclear Information System (INIS)

    Pups used in this study were born to nulliparous, purebred female beagles fed either 17% control (CP) or 8.5% low protein (LP) diets and were given twice daily either 1.8 g/kg ethanol (E) or an equivalent isocaloric dose of sucrose (S) throughout pregnancy. After parturition, all mothers were fed the CP diet and no E or S. On day 1 and each week up to 4 weeks, the weight (WT), crown-rump length (LT) and head circumference (HC) of the pups were measured. These measurements were taken for a post-weaning subset at 6, 8 and 10 weeks. Blood samples were collected each week. At birth, mean WT, LT and HC were significantly lower in pups from E-mothers as compared to S-mothers with either CP or LP diets. The birth WT, LT and HC were significantly lower when mothers were fed LP as compared to the CP diet with either S or E. The prenatal effects of E and LP were significantly associated with lower pup WT, HT and hematocrit values, but not HC up to 4 weeks. At 10 weeks, the growth measurements and hematocrits were significantly lower with prenatal E exposure but not with LP. Pup red cell levels of folate were significantly lower with prenatal E during the first 4 weeks, whereas the effect of prenatal LP but not E was significant at 10 weeks. These data suggest that growth parameters and hematocrit values of pups prenatally exposed to E do not catch up to those of pups from S-mothers fed either diet

  11. TBBPA chronic exposure produces sex-specific neurobehavioral and social interaction changes in adult zebrafish.

    Science.gov (United States)

    Chen, Jiangfei; Tanguay, Robert L; Simonich, Michael; Nie, Shangfei; Zhao, Yuxin; Li, Lelin; Bai, Chenglian; Dong, Qiaoxiang; Huang, Changjiang; Lin, Kuangfei

    2016-01-01

    The toxicity of tetrabromobisphenol A (TBBPA) has been extensively studied because of its high production volume. TBBPA is toxic to aquatic fish based on acute high concentration exposure tests, and few studies have assessed the behavioral effects of low concentration chronic TBBPA exposures in aquatic organisms. The present study defined the developmental and neurobehavioral effects associated with exposure of zebrafish to 0, 5 and 50nM TBBPA during 1-120days post-fertilization (dpf) following by detoxification for four months before the behaviors assessment. These low concentration TBBPA exposures were not associated with malformations and did not alter sex ratio, but resulted in reduced zebrafish body weight and length. Adult behavioral assays indicated that TBBPA exposed males had significantly higher average swim speeds and spent significantly more time in high speed darting mode and less time in medium cruising mode compared to control males. In an adult photomotor response assay, TBBPA exposure was associated with hyperactivity in male fish. Female zebrafish responses in these assays followed a similar trend, but the magnitude of TBBPA effects was generally smaller than in males. Social interaction evaluated using a mirror attack test showed that 50nM TBBPA exposed males had heightened aggression. Females exposed to 50nM TBBPA spent more time in the vicinity of the mirror, but did not show increased aggression toward the mirror compared to unexposed control fish. Overall, the hyperactivity and social behavior deficits ascribed here to chronic TBBPA exposure was most profound in males. Our findings indicate that TBBPA can cause developmental and neurobehavioral deficits, and may pose significant health risk to humans. PMID:27221227

  12. Chronic caffeine exposure attenuates blast-induced memory deficit in mice

    Institute of Scientific and Technical Information of China (English)

    Ya-Lei Ning; Nan Yang; Xing Chen; Zi-Ai Zhao; Xiu-Zhu Zhang; Xing-Yun Chen; Ping Li

    2015-01-01

    Objective:To investigate the effects of three different ways of chronic caffeine administration on blastinduced memory dysfunction and to explore the underlying mechanisms.Methods:Adult male C57BL/6 mice were used and randomly divided into five groups:control:without blast exposure,con-water:administrated with water continuously before and after blast-induced traumatic brain injury (bTBI),con-caffeine:administrated with caffeine continuously for 1 month before and after bTBI,pre-caffeine:chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI,post-caffeine:chronically administrated with caffeine after bTBI.After being subjected to moderate intensity of blast injury,mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1,4,and 8 weeks post-blast injury.Neurological deficit scoring,glutamate concentration,proinflammatory cytokines production,and neuropathological changes at 24 h,1,4,and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages.Adenosine A1 receptor expression was detected using qPCR.Results:All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit,which is correlated with the neuroprotective effects against excitotoxicity,inflammation,astrogliosis and neuronal loss at different stages of injury.Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI;pre-bTBl and post-bTBl treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively.Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.Conclusion:Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get,the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

  13. Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort†

    OpenAIRE

    Mathews, Carol A; Scharf, Jeremiah M.; Miller, Laura L; Macdonald-Wallis, Corrie; Lawlor, Debbie A.; Ben-Shlomo, Yoav

    2014-01-01

    Background Tourette syndrome and chronic tic disorder are heritable but aetiologically complex. Although environment plays a role in their development, existing studies of non-genetic risk factors are inconsistent. Aims To examine the association between pre- and perinatal exposures and Tourette syndrome/chronic tic disorder in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective longitudinal pre-birth cohort. Method Relationships between exposures and Tourette syndrome/ch...

  14. The effect of chronic exposure to highly aggressive mice on hippocampal gene expression of non-aggressive subordinates

    NARCIS (Netherlands)

    Feldker, DEM; Morsink, MC; Veenema, AH; Datson, NA; Proutski, [No Value; Lathouwers, D; de Kloet, ER; Vreugdenhil, E

    2006-01-01

    Exposure to a chronic psychosocial stressor changes the behavioral and neuroendocrine response pattern and causes structural changes in the rodent hippocampus. However, the underlying molecular mechanism of these changes induced by chronic stress is largely unknown. Recently, it was shown that expos

  15. Neurophysiological Assessment of Auditory, Peripheral Nerve, Somatosensory, and Visual System Functions after Developmental Exposure to Ethanol Vapors

    Science.gov (United States)

    Ethanol-blended gasoline entered the market in response to demand for domestic renewable energy sources, and may result in increased inhalation of ethanol vapors in combination with other volatile gasoline constituents. It is important to understand potential risks of inhalation ...

  16. Prenatal exposure to ethanol in rats: effects on liver energy level and antioxidant status in mothers, fetuses, and newborns.

    Science.gov (United States)

    Addolorato, G; Gasbarrini, A; Marcoccia, S; Simoncini, M; Baccarini, P; Vagni, G; Grieco, A; Sbriccoli, A; Granato, A; Stefanini, G F; Gasbarrini, G

    1997-01-01

    The fetal alcohol syndrome is a clinical condition that affects newborns from alcoholic mothers. It is not clear, however, whether ethanol consumption during gestation can affect liver functions of fetuses and newborns. In this study, we aimed to assess the effects of ethanol administration on body weight, liver energy level, and antioxidant status of mothers, fetuses, and newborns. Pregnant rats were exposed to ethanol during the third week of gestation. Body weight, survival, and liver concentration of gluthatione (GSH) and adenosintriphosphate (ATP) were measured. No differences were observed in body weight or in liver ATP and GSH between mothers exposed to ethanol and control animals. Conversely, fetuses from rats exposed to ethanol showed a marked decrease in GSH, ATP, and body weight when compared to those from control rats. Newborns exposed prenatally to ethanol were no different from those born to control mothers. This study suggests that an amount of ethanol that is not sufficient to determine a significant effect on mothers can, nevertheless, cause a marked decrease in growth and in liver antioxidant and energy status in fetuses. These parameters, however, return to control value one week after ethanol discontinuation. PMID:9401672

  17. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov

    2013-12-01

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the

  18. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells

    International Nuclear Information System (INIS)

    Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the relationship

  19. Diffuse parenchymal lung disease in a case of chronic arsenic exposure

    Directory of Open Access Journals (Sweden)

    Somnath Bhattacharya

    2016-01-01

    Full Text Available A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD. Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date.

  20. Effects of chronic occupational exposure to anaesthetic gases on the rate of neutrophil apoptosis among anaesthetists.

    LENUS (Irish Health Repository)

    Tyther, R

    2012-02-03

    BACKGROUND AND OBJECTIVE: Volatile anaesthetic agents are known to influence neutrophil function. The aim was to determine the effect of chronic occupational exposure to volatile anaesthetic agents on the rate of neutrophil apoptosis among anaesthetists. To test this hypothesis, we compared the rate of neutrophil apoptosis in anaesthetists who had been chronically exposed to volatile anaesthetic agents with that in unexposed volunteers. METHODS: Venous blood (20 mL) was withdrawn from 24 ASA I-II volunteers, from which neutrophils were isolated, and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. RESULTS: At 1 h (but not at 12 and 24 h) in culture, the rate of neutrophil apoptosis was significantly less in the anaesthetists--13.8 (12.9%) versus 34.4 (12.1%) (P = 0.001). CONCLUSIONS: Chronic occupational exposure to volatile anaesthetic agents may inhibit neutrophil apoptosis. This may have implications for anaesthetists and similarly exposed healthcare workers in terms of the adequacy of their inflammatory response.

  1. Striatal proteomic analysis suggests that first L-dopa dose equates to chronic exposure.

    Directory of Open Access Journals (Sweden)

    Birger Scholz

    Full Text Available L-3,4-dihydroxypheylalanine (L-dopa-induced dyskinesia represent a debilitating complication of therapy for Parkinson's disease (PD that result from a progressive sensitization through repeated L-dopa exposures. The MPTP macaque model was used to study the proteome in dopamine-depleted striatum with and without subsequent acute and chronic L-dopa treatment using two-dimensional difference in-gel electrophoresis (2D-DIGE and mass spectrometry. The present data suggest that the dopamine-depleted striatum is so sensitive to de novo L-dopa treatment that the first ever administration alone would be able (i to induce rapid post-translational modification-based proteomic changes that are specific to this first exposure and (ii, possibly, lead to irreversible protein level changes that would be not further modified by chronic L-dopa treatment. The apparent equivalence between first and chronic L-dopa administration suggests that priming would be the direct consequence of dopamine loss, the first L-dopa administrations only exacerbating the sensitization process but not inducing it.

  2. Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity.

    Science.gov (United States)

    Maskey, Dhiraj; Pradhan, Jonu; Aryal, Bijay; Lee, Chang-Min; Choi, In-Young; Park, Ki-Sup; Kim, Seok Bae; Kim, Hyung Gun; Kim, Myeung Ju

    2010-07-30

    Exponential interindividual handling in wireless communication system has raised possible doubts in the biological aspects of radiofrequency (RF) exposure on human brain owing to its close proximity to the mobile phone. In the nervous system, calcium (Ca(2+)) plays a critical role in releasing neurotransmitters, generating action potential and membrane integrity. Alterations in intracellular Ca(2+) concentration trigger aberrant synaptic action or cause neuronal apoptosis, which may exert an influence on the cellular pathology for learning and memory in the hippocampus. Calcium binding proteins like calbindin D28-K (CB) is responsible for the maintaining and controlling Ca(2+) homeostasis. Therefore, in the present study, we investigated the effect of RF exposure on rat hippocampus at 835 MHz with low energy (specific absorption rate: SAR=1.6 W/kg) for 3 months by using both CB and glial fibrillary acidic protein (GFAP) specific antibodies by immunohistochemical method. Decrease in CB immunoreactivity (IR) was noted in exposed (E1.6) group with loss of interneurons and pyramidal cells in CA1 area and loss of granule cells. Also, an overall increase in GFAP IR was observed in the hippocampus of E1.6. By TUNEL assay, apoptotic cells were detected in the CA1, CA3 areas and dentate gyrus of hippocampus, which reflects that chronic RF exposure may affect the cell viability. In addition, the increase of GFAP IR due to RF exposure could be well suited with the feature of reactive astrocytosis, which is an abnormal increase in the number of astrocytes due to the loss of nearby neurons. Chronic RF exposure to the rat brain suggested that the decrease of CB IR accompanying apoptosis and increase of GFAP IR might be morphological parameters in the hippocampus damages. PMID:20546709

  3. Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations.

    Science.gov (United States)

    Mrdalj, Jelena; Lundegaard Mattson, Ase; Murison, Robert; Konow Jellestad, Finn; Milde, Anne Marita; Pallesen, Ståle; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2014-03-01

    The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2-14, male Wistar rats (n = 8 per group) were daily separated from their mothers for a period of either 180 min (long maternal separation; LMS) or 10 min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors. PMID:24156523

  4. Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Amie L. Holmes

    2013-11-01

    Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

  5. Reproduction recovery of the crustacean Daphnia magna after chronic exposure to ibuprofen.

    Science.gov (United States)

    Hayashi, Yuya; Heckmann, Lars-Henrik; Callaghan, Amanda; Sibly, Richard M

    2008-05-01

    In mammals, the pharmaceutical ibuprofen (IB), a non-steroidal anti-inflammatory drug, primarily functions by reversibly inhibiting the cyclooxygenase (COX) pathway in the synthesis of eicosanoids (e.g. prostaglandins). Previous studies suggest that IB may act in a similar manner to interrupt production of eicosanoids reducing reproduction in the model crustacean Daphnia magna. On this basis withdrawal of IB should lead to the recovery of D. magna reproduction. Here we test whether the effect of IB is reversible in D. magna, as it is in mammals, by observing reproduction recovery following chronic exposure. D. magna (5-days old) were exposed to a range of IB concentrations (0, 20, 40 and 80 mg l(-1)) for 10 days followed by a 10 day recovery period in uncontaminated water. During the exposure period, individuals exposed to higher concentrations produced significantly fewer offspring. Thereafter, IB-stressed individuals produced offspring faster during recovery, having similar average population growth rates (PGR) (1.15-1.28) to controls by the end of the test. It appears that maternal daphnids are susceptible to IB during egg maturation. This is the first recorded recovery of reproduction in aquatic invertebrates that suffered reproductive inhibition during chronic exposure to a chemical stressor. Our results suggest a possible theory behind the compensatory fecundity that we referred to as 'catch-up reproduction'. PMID:18214676

  6. Metabolic and histopathological alterations in the marine bivalve Mytilus galloprovincialis induced by chronic exposure to acrylamide.

    Science.gov (United States)

    Larguinho, Miguel; Cordeiro, Ana; Diniz, Mário S; Costa, Pedro M; Baptista, Pedro V

    2014-11-01

    Although the neurotoxic and genotoxic potential of acrylamide has been established in freshwater fish, the full breadth of the toxicological consequences induced by this xenobiotic has not yet been disclosed, particularly in aquatic invertebrates. To assess the effects of acrylamide on a bivalve model, the Mediterranean mussel (Mytilus galloprovincialis), two different setups were accomplished: 1) acute exposure to several concentrations of waterborne acrylamide to determine lethality thresholds of the substance and 2) chronic exposure to more reduced acrylamide concentrations to survey phases I and II metabolic endpoints and to perform a whole-body screening for histopathological alterations. Acute toxicity was low (LC50≈400mg/L). However, mussels were responsive to prolonged exposure to chronic concentrations of waterborne acrylamide (1-10mg/L), yielding a significant increase in lipid peroxidation plus EROD and GST activities. Still, total anti-oxidant capacity was not exceeded. In addition, no neurotoxic effects could be determined through acetylcholine esterase (AChE) activity. The findings suggest aryl-hydrocarbon receptor (Ahr)-dependent responses in mussels exposed to acrylamide, although reduced comparatively to vertebrates. No significant histological damage was found in digestive gland or gills but female gonads endured severe necrosis and oocyte atresia. Altogether, the results indicate that acrylamide may induce gonadotoxicity in mussels, although the subject should benefit from further research. Altogether, the findings suggest that the risk of acrylamide to aquatic animals, especially molluscs, may be underestimated. PMID:25262075

  7. Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

    International Nuclear Information System (INIS)

    Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltration was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice

  8. The effect of chronic exposure to tobacco smoke on the antibacterial defenses of the lung.

    Science.gov (United States)

    Huber, G L; Pochay, V E; Mahajan, V K; McCarthy, C R; Hinds, W C; Davies, P; Drath, D B; Sornberger, G C

    1977-01-01

    To evaluate the effects of cigarette smoking on the host defenses of the lung, male CD rats were exposed to fresh whole smoke for up to 60 consecutive days. Intrapulmonary deposition of smoke and animal exposure levels, quantified with decachlorobiphenyl and other smoke tracers, indicated a daily cigarette exposure equivalent to approximately a pack and a half per day in man. Pulmonary alveolar macrophage function in situ was quantified by the inactivation of an aerosolized challenge of Staphylococcus aureus six hours after inoculation. Controls (n=120) inactivated 88.8+/-0.64% of the staphylococci. Exposure to whole smoke did not impair intrapulmonary antistaphylococcal defenses, with inactivation rates of 89.8+/-0.97% (n=49) and 89.1+/-0.46% (n=74) at 30 and 60 days, respectively. Inactivation distribution frequency analysis in controls revealed that 7% of animals had inactivation values greater than two standard deviations from the mean. With prolonged exposure mean with less skewing towards the abnormal. Alveolar macrophages harvested from smoked animals were comparable in viability and in vitro antistaphylococcal activity to controls, appeared to be metabolically activated and had specific stereologic ultrastructural alterations. These studies indicate that chronic exposure to tobacco smoke does not impair, and in fact may stimulate, the host defenses of the lung, as evaluated by in vivo and in vitro pulmonary alveolar macrophage function. PMID:843645

  9. Effects of chronic carbon monoxide exposure on fetal growth and development in mice

    Directory of Open Access Journals (Sweden)

    Venditti Carolina C

    2011-12-01

    Full Text Available Abstract Background Carbon monoxide (CO is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Methods Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Results Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

  10. Persistent modification of Nav1.9 following chronic exposure to insecticides and pyridostigmine bromide

    International Nuclear Information System (INIS)

    Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Nav1.8, but increased Kv7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Nav1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Nav1.9, but significant increases in the amplitude of Nav1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Nav1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Nav1.9 expressed in muscle and vascular nociceptors. The reported increases in Kv7 amplitude may have been an adaptive response to increased Nav1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Nav1.9 and Kv7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were unchanged. • The amplitude and conductance of Nav1.9 were

  11. Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice.

    Science.gov (United States)

    Schweitzer, Paul; Cates-Gatto, Chelsea; Varodayan, Florence P; Nadav, Tali; Roberto, Marisa; Lasek, Amy W; Roberts, Amanda J

    2016-08-01

    Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the brain and implicated in alcohol abuse in humans and behavioral responses to ethanol in mice. Previous studies have shown an association of human ALK with acute responses to alcohol and alcohol dependence. In addition, Alk knockout (Alk -/-) mice consume more ethanol in a binge-drinking test and show increased sensitivity to ethanol sedation. However, the function of ALK in excessive drinking following the establishment of ethanol dependence has not been examined. In this study, we tested Alk -/- mice for dependence-induced drinking using the chronic intermittent ethanol-two bottle choice drinking (CIE-2BC) protocol. We found that Alk -/- mice initially consume more ethanol prior to CIE exposure, but do not escalate ethanol consumption after exposure, suggesting that ALK may promote the escalation of drinking after ethanol dependence. To determine the mechanism(s) responsible for this behavioral phenotype we used an electrophysiological approach to examine GABA neurotransmission in the central nucleus of the amygdala (CeA), a brain region that regulates alcohol consumption and shows increased GABA signaling after chronic ethanol exposure. GABA transmission in ethanol-naïve Alk -/- mice was enhanced at baseline and potentiated in response to acute ethanol application when compared to wild-type (Alk +/+) mice. Moreover, basal GABA transmission was not elevated by CIE exposure in Alk -/- mice as it was in Alk +/+ mice. These data suggest that ALK plays a role in dependence-induced drinking and the regulation of presynaptic GABA release in the CeA. PMID:26946429

  12. Effect of intermittent exposure to ethanol and MDMA during adolescence on learning and memory in adult mice

    Directory of Open Access Journals (Sweden)

    Vidal-Infer Antonio

    2012-06-01

    Full Text Available Abstract Background Heavy binge drinking is increasingly frequent among adolescents, and consumption of 3,4-methylenedioxymethamphetamine (MDMA is often combined with ethanol (EtOH. The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on learning and memory were evaluated in adult mice using the Hebb-Williams maze. Methods Adolescent OF1 mice were exposed to EtOH (1.25 g/kg on two consecutive days at 48-h intervals over a 14-day period (from PD 29 to 42. MDMA (10 or 20 mg/kg was injected twice daily at 4-h intervals over two consecutive days, and this schedule was repeated six days later (PD 33, 34, 41 and 42, resulting in a total of eight injections. Animals were initiated in the Hebb-Williams maze on PND 64. The concentration of brain monoamines in the striatum and hippocampus was then measured. Results At the doses employed, both EtOH and MDMA, administered alone or together, impaired learning in the Hebb-Williams maze, as treated animals required more time to reach the goal than their saline-treated counterparts. The groups treated during adolescence with EtOH, alone or plus MDMA, also presented longer latency scores and needed more trials to reach the acquisition criterion score. MDMA induced a decrease in striatal DA concentration, an effect that was augmented by the co-administration of EtOH. All the treatment groups displayed an imbalance in the interaction DA/serotonin. Conclusions The present findings indicate that the developing brain is highly vulnerable to the damaging effects of EtOH and/or MDMA, since mice receiving these drugs in a binge pattern during adolescence exhibit impaired learning and memory in adulthood.

  13. Quantifying Chronic Stress Exposure for Cumulative Risk Assessment: Lessons Learned from a Case Study of Allostatic Load

    Science.gov (United States)

    Although multiple methods of quantifying environmental chemical exposures have been validated for use in human health risk assessment, quantifying chronic stress exposure is more challenging. Stress is a consequence of perceiving an “exposure” (e.g., violence, poverty) as more th...

  14. NEUROPEPTIDE Y (NPY) SUPPRESSES ETHANOL DRINKING IN ETHANOL-ABSTINENT, BUT NOT NON-ETHANOL-ABSTINENT, WISTAR RATS

    OpenAIRE

    Gilpin, N W; Stewart, R B; Badia-Elder, N.E.

    2008-01-01

    In outbred rats, increases in brain neuropeptide Y (NPY) activity suppress ethanol consumption in a variety of access conditions, but only following a history of ethanol dependence. NPY reliably suppresses ethanol drinking in alcohol-preferring (P) rats and this effect is augmented following a period of ethanol abstinence. The purpose of this experiment was to examine the effects of NPY on 2-bottle choice ethanol drinking and feeding in Wistar rats that had undergone chronic ethanol vapor exp...

  15. Therapeutic effectiveness and safety parathyroid adenoma ablation with percutaneous ethanol injection under sonographic guidance in patients with chronic renal failure and secondary hyperparathyroidism refractory to medical treatment

    International Nuclear Information System (INIS)

    Secondary hyperparathyroidism unresponsive to medical treatment is a common complication in patients with chronic renal failure and prolonged dialysis therapy, which requires surgery of the parathyroid glands, with the risks and costs of surgery. Objective: To evaluate the therapeutic effectiveness and safety of ablation of parathyroid adenomas by percutaneous ethanol injection under ultrasound guidance. Method: After approval by the institutional medical ethics committee, informed written consent was obtained in 15 patients who met the inclusion criteria. Sonographically guided ethanol was injected consecutively into adenomas, with an interval of time less than six months. Results: Size, Doppler vascularity of adenomas, and the levels of parathyroid hormone, calcium and phosphorus were measured before and after ablation as criteria for treatment response in 15 patients. Of all patients, six (40%) had no therapeutic response. Therapeutic response was observed in nine patients (60%). In the latter group, five patients (33.3%) had successful response and symptomatic improvement, in two patients (13.3%), therapeutic response was suboptimal, and in two patients (13.3%), the response was unsatisfactory. The procedure was safe. Local pain, transient dysphonia and cough were considered minor complications and were the most common, with resolution in all cases. There were no major complications. Conclusion: Ablation of parathyroid adenomas with percutaneous ethanol injection and ultrasound guidance, in uremic patients with secondary hyperparathyroidism unresponsive to medical treatment is an effective and safe therapy. Studies involving more patients and longer follow up are needed in order to stablish more conclusive results

  16. Reduced gene expression levels after chronic exposure to high concentrations of air pollutants

    Czech Academy of Sciences Publication Activity Database

    Rössner ml., Pavel; Tulupová, Elena; Rössnerová, Andrea; Líbalová, Helena; Hoňková, Kateřina; Gmuender, H.; Pastorková, Anna; Švecová, Vlasta; Topinka, Jan; Šrám, Radim

    2015-01-01

    Roč. 780, oct (2015), s. 60-70. ISSN 0027-5107 R&D Projects: GA MŽP(CZ) SP/1B3/8/08; GA MŠk(CZ) LO1508; GA ČR GA13-13458S; GA MŠk 2B08005 Institutional support: RVO:68378041 Keywords : chronic exposure * air pollution * gene expression profiles * human health * particulate matter * polycyclic aromatic hydrocarbons Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.680, year: 2014

  17. Chronic exposure to a beta 2-adrenoceptor agonist increases the airway response to methacholine.

    Science.gov (United States)

    Witt-Enderby, P A; Yamamura, H I; Halonen, M; Palmer, J D; Bloom, J W

    1993-09-01

    Scheduled chronic administration of beta 2-adrenoceptor agonist bronchodilators in patients with asthma recently has been reported to be associated with a worsening of symptoms and an increase in bronchial responsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (beta 2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in vitro tissue bath techniques, that in mainstem bronchi from rabbits given a 28-day exposure to albuterol, maximum contraction to methacholine was increased in the albuterol-treated group (control group = 1.10 +/- 0.11 g vs. treated group = 1.50 +/- 0.13 g, P airway smooth muscle to methacholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7901034

  18. Growth Responses of Fish During Chronic Exposure of Metal Mixture under Laboratory Conditions

    Directory of Open Access Journals (Sweden)

    Saima Naz and Muhammad Javed

    2013-07-01

    Full Text Available Growth responses of five fish species viz. Catla catla, Labeo rohita, Cirrhina mrigala, Ctenopharyngodon idella and Hypophthalmichthys molitrix were determined, separately, under chronic exposure of binary mixture of metals (Zn+Ni at sub-lethal concentrations (1/3rd of LC50 for 12 weeks. Randomized complete block design (RCBD was followed to conduct this research work. The groups (10 fish each of Catla catla, Labeo rohita, Cirrhina mrigala, Ctenopharyngodon idella and Hypophthalmichthys molitrix having almost similar weights were investigated for their growth responses and metals bioaccumulation patterns in their body organs during chronic exposure of Zn+Ni mixture. The bioaccumulation of metals in the fish body organs viz. gills, liver, kidney, fins, bones, muscle and skin were also determined before and after growth trails under the stress of metals mixture. The exposure of fish to sub-lethal concentrations of mixture caused significant impacts on the average wet weight increments of five fish species. Ctenopharyngodon idella and Labeo rohita attained significantly higher weights, followed by that of Hypophthalmichthys molitrix, Cirrhina mrigala and Catla catla. However, the growth of metals mixture exposed fish species was significantly lesser than that of control fish (un-stressed. Significantly variable condition factor values reflected the degree of fish well-beings that correlated directly with fish growth and metal exposure concentration. Any significant change in feed intake, due to stress, is reflected in terms of fish growth showing the impacts of metal mixture on fish growth were either additive or antagonist / synergistic. Accumulation of all the metals in fish body followed the general order: liver>kidney>gills> skin >muscle> fins >bones.

  19. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus).

    Science.gov (United States)

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L(-1) for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The OCRs in all groups were significantly different than control (P muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained. PMID:27382568

  20. Effect of chronic and subchronic organic solvents exposure on balance control of workers in plant manufacturing adhesive materials.

    Science.gov (United States)

    Herpin, Guillaume; Gargouri, Imed; Gauchard, Gérome C; Nisse, Catherine; Khadhraoui, Moncef; Elleuch, Boubaker; Zmirou-Navier, Denis; Perrin, Philippe P

    2009-02-01

    High-level occupational exposure to volatile organic solvents may elicit neurotoxic effects, especially on central and peripheral structures involved in balance ability. Studies on balance control in relation with exposure levels close to the threshold limit values are scarce. This study aimed to assess the neurotoxic effects of chronic and subchronic exposure to organic solvents among workers in plant manufacturing adhesive materials. Balance control was evaluated in 18 subjects, mainly exposed to n-hexane and toluene, with current median exposure levels of 222 and 102 mg/m(3), respectively, and a median exposure duration of 21 years, and in 32 nonexposed controls, using posturography tests with and without sensory conflicting situations. Tests were undergone at the beginning of the work shift (chronic exposure) following a week end, and after 72 h (subchronic exposure). Balance control performance was lower in chronically exposed workers compared to controls, and got worse after subchronic exposure, particularly during situations, where vestibular information was important. Our study suggests that a low-level and prolonged exposure to volatile organic solvents, mainly n-hexane and toluene, in the workplace is associated with deleterious central effects involved in postural regulation. This neurotoxicity is characterized by difficulties to use the most relevant information to control balance, leading to altered management of sensory conflicting situations. PMID:19384580

  1. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.

    Science.gov (United States)

    Johnson, Jill R; Wiley, Ryan E; Fattouh, Ramzi; Swirski, Filip K; Gajewska, Beata U; Coyle, Anthony J; Gutierrez-Ramos, José-Carlos; Ellis, Russ; Inman, Mark D; Jordana, Manel

    2004-02-01

    It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly. PMID:14597485

  2. Investigations of subclinical neurogenous damage of persons with chronic occupational exposure to lead and trichlorethylene

    Energy Technology Data Exchange (ETDEWEB)

    Reichenbach, T.

    1980-12-15

    The functions of the peripheral nervous system, for example the maximum and minimum conduction velocities of the ulnar and the radial nerves, were measured in 22 men and 9 women with occupational exposure to lead and in 20 men and 20 women without occupational exposure to lead. The result of the comparison of the obtained measuring values was a decrease of the minimum conduction velocity of the ulnar nerve of the working hand of men exposed to lead. In order to quantify the lead exposure we determined in all test persons the blood lead level, the concentration of free erythrocyteporphyrines in the blood and the hemoglobin concentration. The study reports also about the elcetroneurographic investigations on 7 persons with chronical exposure to trichloroethylene and on 13 comparable persons of a corresponding age group. A correlation between the biochemical and toxicologic parameters and the nervous conduction velocities could be detected neither in the persons exposed to lead nor in those exposed to trichloroethylene. The measured nervous conduction velocities are well comparable with those age-specific indications given in the specialised literature. The dependence of conduction velocity on various parameters as age, temperature, left- or righthandedness and sex is discussed.

  3. CCL2-ethanol interactions and hippocampal synaptic protein expression in a transgenic mouse model

    OpenAIRE

    Gruol, Donna L.; Vo, Khanh; Bray, Jennifer G.; Roberts, Amanda J.

    2014-01-01

    Chronic exposure to ethanol produces a number of detrimental effects on behavior. Neuroadaptive changes in brain structure or function underlie these behavioral effects and may be transient or persistent in nature. Central to the functional changes are alterations in the biology of neuronal and glial cells of the brain. Recent data show that ethanol induces glial cells of the brain to produce elevated levels of neuroimmune factors including CCL2, a key innate immune chemokine. Depending on th...

  4. Effects of a chronic lower range of triclosan exposure to a stream mesocosm community

    Science.gov (United States)

    Nietch, C.T.; Quinlan, E.L.; Lazorchak, J.; Impellitteri, C.; Raikow, D.; Walters, David M.

    2013-01-01

    Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is an antimicrobial found in consumer soaps and toothpaste. It is in treated wastewater effluents at low part per billion concentrations, representing a potentially chronic exposure condition for biota inhabiting receiving streams. A naturally colonized benthos was created using flow-through indoor mesocosms. Then the benthic communities were dosed to achieve different in-stream triclosan concentrations (Control, 0.1, 0.5, 1.0, 5.0, and 10 µg/L) for 56 days. Water quality parameters and endpoints from bacteria to macroinvertebrates plus interacting abiotic components were measured. Effects of triclosan on specific microbial endpoints were observed at all doses, including an effect on litter decomposition dynamics at doses 1.0 µg/L and higher. Resistance of periphytic bacteria to triclosan significantly increased in doses 0.5 µg/L and above. By the end of dosing, the antimicrobial appeared to stimulate the stream periphyton at the three lowest doses while the two highest doses exhibited decreased stocks of periphyton, including significantly lower bacteria cell densities, and cyanobacteria abundance compared to the control. Beside an effect on benthic ostracods, the changes that occurred in the periphyton did not translate to significant change in the colonizing nematodes, the macroinvertebrate community as a whole, or other measurements of stream function. The results shed light on the role a low, chronic exposure to triclosan may play in effluent dominated streams.

  5. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  6. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants.

    Science.gov (United States)

    Reichwaldt, Elke S; Stone, Daniel; Barrington, Dani J; Sinang, Som C; Ghadouani, Anas

    2016-01-01

    Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a 'high' risk to develop Day Away From Work illness, and lakes that present a 'low' or 'medium' risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants. PMID:27589798

  7. Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure.

    Science.gov (United States)

    Pan, Zhengqi; Zhang, Xianrong; Shangguan, Yangfan; Hu, Hang; Chen, Liaobin; Wang, Hui

    2016-08-15

    Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showed a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. PMID:27338645

  8. Effects of Chronic Exposure to Sodium Arsenate on Kidney of Rats

    Directory of Open Access Journals (Sweden)

    Namdar Yousofvand

    2015-09-01

    Full Text Available Background: In the present study, histopathological effects of chronic exposure to sodium arsenate in drinkable water were studied on a quantity of organs of rat. Methods: Rats were divided into two groups, group I; served as control group, were main-tained on deionized drinkable water for 2 months, and group II; the study group were given 60 g/ml of sodium arsenate in deionized drinkable water for 2 months. Blood and urine samples from two groups of animals were collected under anesthesia and the animals were sacrificed under deep anesthesia (a-chloralose, 100 mg/kg, I.P. Their kidney, liver, aorta, and heart were dissected out and cleaned of surrounding connective tissue. The organs were kept in formaldehyde (10% for histopathologic examination. Serum and urine samples from two groups were collected and analyzed for arsenic level. Total quantity of arsenic in serum and urine of animal was measured through graphic furnace atomic absorption spectrometry (GF-AAS. Results:Examination with light microscopy did not show any visible structural changes in the aorta, myocardium, and liver of chronic arsenic treated animals.However, a significant effect was observed in the kidneys of chronic arsenic treated rats showing distinct changes in proxi-mal tubular cells. There was high concentration of arsenic in serum and urine of arsenic ex-posed animals (group II significantly (P<0.001. Conclusion:Swollen tubular cells in histopathologic study of kidney may suggest toxic effects of arsenic in the body.

  9. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats

    Indian Academy of Sciences (India)

    Ashok Iyyaswamy; Sheeladevi Rathinasamy

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  10. Analysis of dose-rate effects on cellular responses to chronic radiation exposure

    International Nuclear Information System (INIS)

    The effects in the title were studied on their expression of various genes concerned with radiation exposure by the acute (1 Gy/min) and chronic (0.007-0.694 Gy/min) irradiations to various cell lines. Cell of human origin were the primarily cultured fibroblasts (F), their immortalized strain (imF) by transduction of human teromerase transcriptase (hTERT), breast cancer MCF-7, osteosarcoma U-20S, colon cancer HCT-116 and T-cell leukemia Jurkat. Acute irradiation was done in a gamma-cell with Cs-137 gamma-ray and chronic one, in a CO2-incubator with the Cs-137 source. Expression of genes was analyzed by mRNA sequence with Genome Analyzer. Proteins of p53, p53-Ser15-P, murine double minute 2 (MDM2), p21 and a/b-tubulin were analyzed by Western blotting. D0 values of acute irradiation were found in the range of 1.1-1.4 Gy, suggesting the similar sensitivity of used cells. However, responses to chronic exposure were different from cells to cells: particularly, at 0.347 mGy/min, no effect on growth was observed in cancer-derived cells until 10 days whereas a marked growth inhibition of F and imF cells was seen after 4 days. Arrest of proliferation of F cells after 10 days exposure at 0.347 mGy/min was tentative, but at 0.694 mGy/min, it was irreversible dependently on the exposure time. They were arrested at G0 stage. Gene expression analyzed by mRNA sequence was shown to be changed even by the lowest rate 0.007 mGy/min: levels of protein expressed under control of cancer-suppressing p53 were markedly altered. Western blotting showed an increased expression of examined proteins except for p53, at higher dose than 0.069 mGy/min. Results indicated that the cellular response to radiation involved not only DNA damage but also the process of yielding the damage. (T.T.)

  11. Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice.

    Science.gov (United States)

    Shearn, Colin T; Fritz, Kristofer S; Shearn, Alisabeth H; Saba, Laura M; Mercer, Kelly E; Engi, Bridgette; Galligan, James J; Zimniak, Piotr; Orlicky, David J; Ronis, Martin J; Petersen, Dennis R

    2016-04-01

    Chronic alcohol consumption induces hepatic oxidative stress resulting in production of highly reactive electrophilic α/β-unsaturated aldehydes that have the potential to modify proteins. A primary mechanism of reactive aldehyde detoxification by hepatocytes is through GSTA4-driven enzymatic conjugation with GSH. Given reports that oxidative stress initiates GSTA4 translocation to the mitochondria, we hypothesized that increased hepatocellular damage in ethanol (EtOH)-fed GSTA4(-/-) mice is due to enhanced mitochondrial protein modification by reactive aldehydes. Chronic ingestion of EtOH increased hepatic protein carbonylation in GSTA4(-/-) mice as evidenced by increased 4-HNE and MDA immunostaining in the hepatic periportal region. Using mass spectrometric analysis of biotin hydrazide conjugated carbonylated proteins, a total of 829 proteins were identified in microsomal, cytosolic and mitochondrial fractions. Of these, 417 were novel to EtOH models. Focusing on mitochondrial fractions, 1.61-fold more carbonylated proteins were identified in EtOH-fed GSTA4(-)(/-) mice compared to their respective WT mice ingesting EtOH. Bioinformatic KEGG pathway analysis of carbonylated proteins from the mitochondrial fractions revealed an increased propensity for modification of proteins regulating oxidative phosphorylation, glucose, fatty acid, glutathione and amino acid metabolic processes in GSTA4(-/-) mice. Additional analysis revealed sites of reactive aldehyde protein modification on 26 novel peptides/proteins isolated from either SV/GSTA4(-/-) PF or EtOH fed mice. Among the peptides/proteins identified, ACSL, ACOX2, MTP, and THIKB contribute to regulation of fatty acid metabolism and ARG1, ARLY, and OAT, which regulate nitrogen and ammonia metabolism having direct relevance to ethanol-induced liver injury. These data define a role for GSTA4-4 in buffering hepatic oxidative stress associated with chronic alcohol consumption and that this GST isoform plays an important

  12. Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice

    Directory of Open Access Journals (Sweden)

    Colin T. Shearn

    2016-04-01

    Full Text Available Chronic alcohol consumption induces hepatic oxidative stress resulting in production of highly reactive electrophilic α/β-unsaturated aldehydes that have the potential to modify proteins. A primary mechanism of reactive aldehyde detoxification by hepatocytes is through GSTA4-driven enzymatic conjugation with GSH. Given reports that oxidative stress initiates GSTA4 translocation to the mitochondria, we hypothesized that increased hepatocellular damage in ethanol (EtOH-fed GSTA4−/− mice is due to enhanced mitochondrial protein modification by reactive aldehydes. Chronic ingestion of EtOH increased hepatic protein carbonylation in GSTA4−/− mice as evidenced by increased 4-HNE and MDA immunostaining in the hepatic periportal region. Using mass spectrometric analysis of biotin hydrazide conjugated carbonylated proteins, a total of 829 proteins were identified in microsomal, cytosolic and mitochondrial fractions. Of these, 417 were novel to EtOH models. Focusing on mitochondrial fractions, 1.61-fold more carbonylated proteins were identified in EtOH-fed GSTA4−/− mice compared to their respective WT mice ingesting EtOH. Bioinformatic KEGG pathway analysis of carbonylated proteins from the mitochondrial fractions revealed an increased propensity for modification of proteins regulating oxidative phosphorylation, glucose, fatty acid, glutathione and amino acid metabolic processes in GSTA4−/− mice. Additional analysis revealed sites of reactive aldehyde protein modification on 26 novel peptides/proteins isolated from either SV/GSTA4−/− PF or EtOH fed mice. Among the peptides/proteins identified, ACSL, ACOX2, MTP, and THIKB contribute to regulation of fatty acid metabolism and ARG1, ARLY, and OAT, which regulate nitrogen and ammonia metabolism having direct relevance to ethanol-induced liver injury. These data define a role for GSTA4-4 in buffering hepatic oxidative stress associated with chronic alcohol consumption and that this GST

  13. Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure

    International Nuclear Information System (INIS)

    Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 µg cm−2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the

  14. Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure

    Science.gov (United States)

    Zhang, Hanyuan; Lohcharoenkal, Warangkana; Sun, Jianbo; Li, Xiang; Wang, Liying; Wu, Nianqiang; Rojanasakul, Yon; Liu, Yuxin

    2016-01-01

    Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 μg cm−2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the

  15. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

    Science.gov (United States)

    Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

    1998-01-01

    In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

  16. Environmental heavy metal exposure and chronic kidney disease in the general population.

    Science.gov (United States)

    Kim, Nam Hee; Hyun, Young Youl; Lee, Kyu-Beck; Chang, Yoosoo; Ryu, Seungho; Rhu, Seungho; Oh, Kook-Hwan; Ahn, Curie

    2015-03-01

    Lead (Pb), mercury (Hg), and cadmium (Cd) are common heavy metal toxins and cause toxicological renal effects at high levels, but the relevance of low-level environmental exposures in the general population is controversial. A total of 1,797 adults who participated in the KNHANES (a cross-sectional nationally representative survey in Korea) were examined, and 128 of them (7.1%) had chronic kidney disease (CKD). Our study assessed the association between Pb, Hg, Cd exposure, and CKD. Blood Pb and Cd levels were correlated with CKD in univariate logistic regression model. However, these environmental heavy metals were not associated with CKD after adjustment for age, sex, BMI, smoking, hyperlipidemia, hypertension, diabetes, and these metals in multivariate logistic regression models. We stratified the analysis according to hypertension or diabetes. In the adults with hypertension or diabetes, CKD had a significant association with elevated blood Cd after adjustment, but no association was present with blood Pb and Hg. The corresponding odds ratio [OR] of Cd for CKD were 1.52 (95% confidence interval [CI], 1.05-2.19, P=0.026) in adults with hypertension and 1.92 (95% CI, 1.14-3.25, P=0.014) in adults with diabetes. Environmental low level of Pb, Hg, Cd exposure in the general population was not associated with CKD. However, Cd exposure was associated with CKD, especially in adults with hypertension or diabetes. This finding suggests that environmental low Cd exposure may be a contributor to the risk of CKD in adults with hypertension or diabetes. PMID:25729249

  17. Metallothionein (MT) response after chronic palladium exposure in the zebra mussel, Dreissena polymorpha

    International Nuclear Information System (INIS)

    The effects of different exposure concentrations of palladium (Pd) on relative metallothionein (MT) response and bioaccumulation were investigated in zebra mussels (Dreissena polymorpha). The mussels were exposed to 0.05, 5, 50, and 500 μg/L Pd2+ for 10 weeks under controlled temperature and fasting conditions. Relative MT contents were assessed by a modified Ag-saturation method, which allows to discriminate between MT bound to Pd (Pd-MT) and MT bound to unidentified metals (Ag-MT). Determination of metal contents resulted from atomic absorption spectrometry following a microwave digestion. For unexposed mussels and mussels exposed to 0.05 μg/L Pd no metal accumulation could be detected. All other exposure concentrations resulted in detectable Pd accumulation in mussels with final tissue concentrations of 96 μg/g (500 μg/L), 45 μg/g (50 μg/L), and 9 μg/g (5 μg/L). Compared with initial levels Pd-MT concentrations at the end of the exposure period were 600 (500 μg/L), 160 (50 μg/L), and 27 (5 μg/L) times higher. These results show that an increase in MTs in D. polymorpha already occurs at relatively low aqueous Pd concentrations indicating that there is the need for detoxification of Pd in the mussel. Furthermore, correlations between Ag-MT and Pd accumulation indicate that higher exposure concentrations are associated with adverse effects on the mussels. Thus, harmful effects of chronic Pd exposure of organisms even in lowest concentrations cannot be excluded in the environment

  18. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    International Nuclear Information System (INIS)

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a ‘2-hit’ paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: ► Characterizes a mouse model of arsenic enhanced NAFLD. ► Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. ► This effect is associated with increased inflammation.

  19. Chronic Exposure to Bisphenol A Affects Uterine Function During Early Pregnancy in Mice.

    Science.gov (United States)

    Li, Quanxi; Davila, Juanmahel; Kannan, Athilakshmi; Flaws, Jodi A; Bagchi, Milan K; Bagchi, Indrani C

    2016-05-01

    Environmental and occupational exposure to bisphenol A (BPA), a chemical widely used in polycarbonate plastics and epoxy resins, has received much attention in female reproductive health due to its widespread toxic effects. Although BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In this study, we addressed the effect of prolonged exposure to an environmental relevant dose of BPA on embryo implantation and establishment of pregnancy. Our studies revealed that treatment of mice with BPA led to improper endometrial epithelial and stromal functions thus affecting embryo implantation and establishment of pregnancy. Upon further analyses, we found that the expression of progesterone receptor (PGR) and its downstream target gene, HAND2 (heart and neural crest derivatives expressed 2), was markedly suppressed in BPA-exposed uterine tissues. Previous studies have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor and the MAPK signaling pathways and inhibiting epithelial proliferation. Interestingly, we observed that down-regulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with enhanced activation of fibroblast growth factor and MAPK signaling in the epithelium, thus contributing to aberrant proliferation and lack of uterine receptivity. Further, the differentiation of endometrial stromal cells to decidual cells, an event critical for the establishment and maintenance of pregnancy, was severely compromised in response to BPA. In summary, our studies revealed that chronic exposure to BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy. PMID:27022677

  20. Decision-making about chronic radiation exposure to the public. New recommendations from the ICRP

    International Nuclear Information System (INIS)

    The paper discusses decision-making in situations of chronic exposure within the framework of a forthcoming related ICRP report on the subject which has been produced by an ICRP Task Group chaired by the author. This ICRP report will provide guidance on the application of the ICRP System of Radiological Protection to prolonged exposure situations afflicting members of the public. It will address the general application of the System to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations, and will provide recommendations on generic reference levels for such interventions. It will also consider some specific situations and will discuss a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain relatively high levels of radioactive substances. Annexes will provide some examples of prolonged exposure situations and will discuss the radiological protection quantities, radiation-induced health effects and aspects of the System of Radiological Protection relevant to prolonged exposure. The quantitative recommendations for prolonged exposures provided in the report will be as follows: generic reference levels for intervention, in terms of existing annual doses, of < or approx. 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and of < or approx.10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary); intervention exemption levels for

  1. Chronic neonicotinoid pesticide exposure and parasite stress differentially affects learning in honeybees and bumblebees.

    Science.gov (United States)

    Piiroinen, Saija; Goulson, Dave

    2016-04-13

    Learning and memory are crucial functions which enable insect pollinators to efficiently locate and extract floral rewards. Exposure to pesticides or infection by parasites may cause subtle but ecologically important changes in cognitive functions of pollinators. The potential interactive effects of these stressors on learning and memory have not yet been explored. Furthermore, sensitivity to stressors may differ between species, but few studies have compared responses in different species. Here, we show that chronic exposure to field-realistic levels of the neonicotinoid clothianidin impaired olfactory learning acquisition in honeybees, leading to potential impacts on colony fitness, but not in bumblebees. Infection by the microsporidian parasiteNosema ceranaeslightly impaired learning in honeybees, but no interactive effects were observed.Nosemadid not infect bumblebees (3% infection success). Nevertheless,Nosema-treated bumblebees had a slightly lower rate of learning than controls, but faster learning in combination with neonicotinoid exposure. This highlights the potential for complex interactive effects of stressors on learning. Our results underline that one cannot readily extrapolate findings from one bee species to others. This has important implications for regulatory risk assessments which generally use honeybees as a model for all bees. PMID:27053744

  2. Chronic toxicity of heavy fuel oils to fish embryos using multiple exposure scenarios.

    Science.gov (United States)

    Martin, Jonathan D; Adams, Julie; Hollebone, Bruce; King, Thomas; Brown, R Stephen; Hodson, Peter V

    2014-03-01

    The chronic toxicity to rainbow trout (Oncorhynchus mykiss) embryos of heavy fuel oil (HFO) 6303, weathered HFO 6303, HFO 7102, and medium South American (MESA) crude oil was assessed by different exposure regimes. These included water accommodated fractions (WAF; water in contact with floating oil), chemically enhanced WAF (CEWAF; oil dispersed with Corexit 9500), and effluent from columns of gravel coated with stranded oil. Heavy fuel oil WAF was nontoxic and did not contain detectable concentrations of hydrocarbons, likely because the high density and viscosity of HFO prevented droplet formation. In contrast, chemically dispersed HFO and effluent from columns of stranded HFO contained measurable concentrations of alkyl polycyclic aromatic hydrocarbons (PAH), coincident with embryo toxicity. These exposure regimes enhanced the surface area of oil in contact with water, facilitating oil-water partitioning of hydrocarbons. Heavy fuel oil was consistently more toxic to fish than crude oil and the rank order of alkyl PAH concentrations in whole oil were sufficient to explain the rank order of toxicity, regardless of exposure method. Thus, the propensity of HFO to sink and strand in spawning shoals creates a long-term risk to developing fish because of the sustained release of PAHs from HFO to interstitial waters. Further, PAH monitoring is key to accurate risk assessment. PMID:24464524

  3. Histopathologic alterations associated with global gene expression due to chronic dietary TCDD exposure in juvenile zebrafish.

    Directory of Open Access Journals (Sweden)

    Qing Liu

    Full Text Available The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb and male (18.04 ppb fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption.

  4. Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris).

    Science.gov (United States)

    Moffat, Christopher; Pacheco, Joao Goncalves; Sharp, Sheila; Samson, Andrew J; Bollan, Karen A; Huang, Jeffrey; Buckland, Stephen T; Connolly, Christopher N

    2015-05-01

    The global decline in the abundance and diversity of insect pollinators could result from habitat loss, disease, and pesticide exposure. The contribution of the neonicotinoid insecticides (e.g., clothianidin and imidacloprid) to this decline is controversial, and key to understanding their risk is whether the astonishingly low levels found in the nectar and pollen of plants is sufficient to deliver neuroactive levels to their site of action: the bee brain. Here we show that bumblebees (Bombus terrestris audax) fed field levels [10 nM, 2.1 ppb (w/w)] of neonicotinoid accumulate between 4 and 10 nM in their brains within 3 days. Acute (minutes) exposure of cultured neurons to 10 nM clothianidin, but not imidacloprid, causes a nicotinic acetylcholine receptor-dependent rapid mitochondrial depolarization. However, a chronic (2 days) exposure to 1 nM imidacloprid leads to a receptor-dependent increased sensitivity to a normally innocuous level of acetylcholine, which now also causes rapid mitochondrial depolarization in neurons. Finally, colonies exposed to this level of imidacloprid show deficits in colony growth and nest condition compared with untreated colonies. These findings provide a mechanistic explanation for the poor navigation and foraging observed in neonicotinoid treated bumblebee colonies. PMID:25634958

  5. Novel 14S,21-dihydroxy-docosahexaenoic acid Rescues Wound Healing and Associated Angiogenesis Impaired by Acute Ethanol Intoxication/Exposure

    OpenAIRE

    Tian, Haibin; Lu, Yan; Shah, Shraddha P.; Hong, Song

    2010-01-01

    Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here we found that AE diminished the formation of novel reparative lipid mediator 14S,21-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21-diHDHA) and its biosynthetic intermediate 14S-hydroxy-DHA (14S-HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21-HDHA. These results indicate that in the b...

  6. Preventive effects of geranylgeranylacetone on rat ethanol-induced gastritis

    OpenAIRE

    Ning, Jian-Wen; Lin, Guan-Bin; Ji, Feng; Xu, Jia; Sharify, Najeeb

    2012-01-01

    AIM: To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis.

  7. Kalrn promoter usage and isoform expression respond to chronic cocaine exposure

    Directory of Open Access Journals (Sweden)

    Ma Xin-Ming

    2011-02-01

    Full Text Available Abstract Background The long-term effects of cocaine on behavior are accompanied by structural changes in excitatory glutamatergic synapses onto the medium spiny neurons of the striatum. The Kalrn gene encodes several functionally distinct isoforms; these multidomain guanine nucleotide exchange factors (GEFs contain additional domains known to interact with phosphatidylinositides as well as with a number of different proteins. Through their activation of Rho proteins and their interactions with other proteins, the different Kalirin isoforms affect cytoskeletal organization. Chronic exposure of adult male rodents to cocaine increases levels of Kalirin 7 in the striatum. When exposed chronically to cocaine, mice lacking Kalirin 7, the major adult isoform, fail to show an increase in dendritic spine density in the nucleus accumbens, show diminished place preference for cocaine, and exhibit increased locomotor activity in response to cocaine. Results The use of alternate promoters and 3'-terminal exons of the mouse Kalrn gene were investigated using real-time quantitative polymerase chain reaction. While the two most distal full-length Kalrn promoters are used equally in the prefrontal cortex, the more proximal of these promoters accounts for most of the transcripts expressed in the nucleus accumbens. The 3'-terminal exon unique to the Kalirin 7 isoform accounts for a greater percentage of the Kalrn transcripts in prefrontal cortex than in nucleus accumbens. Western blot analyses confirmed these differences. Chronic cocaine treatment increases usage of the promoter encoding the Δ-Kalirin isoforms but does not alter full-length Kalirin promoter usage. Usage of the 3'-terminal exon unique to Kalirin 7 increases following chronic cocaine exposure. Conclusions Kalrn promoter and 3'-terminal exon utilization are region-specific. In the nucleus accumbens, cocaine-mediated alterations in promoter usage and 3'-terminal exon usage favor expression of

  8. Chronic neonatal nicotine exposure increases excitation in the young adult rat hippocampus in a sex-dependent manner

    OpenAIRE

    Damborsky, Joanne C.; Griffith, William H.; Ursula H Winzer-Serhan

    2011-01-01

    Smoking during pregnancy exposes the fetus to nicotine, resulting in nicotine-stimulated neurotransmitter release. Recent evidence suggests that the hippocampus develops differently in males and females with delayed maturation in males. We show that chronic nicotine exposure during the first postnatal week has sex-specific long-term effects. Neonatal rat pups were chronically treated with nicotine (6 mg/kg/day) (CNN) from postnatal day 1 to 7 or milk only (Controls), and hippocampal slices we...

  9. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.

    Science.gov (United States)

    Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

  10. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn) Exposure on Sea Cucumbers (Apostichopus japonicus)

    OpenAIRE

    Li, Li; Tian, Xiangli; Yu, Xiao; Dong, Shuanglin

    2016-01-01

    Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus) exposed to heavy metals. Acute toxicity values (96 h LC50) were 2.697, 0.133, and 1.574 mg L−1 for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR) decreased. The...

  11. Assessing Cumulative Thermal Stress in Fish During Chronic Exposure to High Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Bevelhimer, M.S.; Bennett, W.R.

    1999-11-14

    As environmental laws become increasingly protective, and with possible future changes in global climate, thermal effects on aquatic resources are likely to receive increasing attention. Lethal temperatures for a variety of species have been determined for situations where temperatures rise rapidly resulting in lethal effects. However, less is known about the effects of chronic exposure to high (but not immediately lethal) temperatures and even less about stress accumulation during periods of fluctuating temperatures. In this paper we present a modeling framework for assessing cumulative thermal stress in fish. The model assumes that stress accumulation occurs above a threshold temperature at a rate depending on the degree to which the threshold is exceeded. The model also includes stress recovery (or alleviation) when temperatures drop below the threshold temperature as in systems with large daily variation. In addition to non-specific physiological stress, the model also simulates thermal effects on growth.

  12. [Influence of chronic lead exposure on resistence to bacterial infection (author's transl)].

    Science.gov (United States)

    Ewers, U; Weisser, L; Wegner, A

    1980-01-01

    Suppression by lead of resistance to bacterial or viral infections has been reported by several authors. We have studied, if a decrease of resistance to bacterial infection could be evaluated at blood lead concentrations (PbB), which correspond to the upper levels of environmental or occupational lead exposure regarded as tolerable (PbB = 35 resp. 60 microgram/100 ml). NMRI mice were chronically exposed to lead by feeding with lead acetate containing diets and given a challenge with Salmonella typhimurium. No increase of susceptibility to bacterial infection could be demonstrated at PbB 100 microgram/100 g, however, an increase of lethality and a decrease of 50% survival times could be observed after bacterial infection. PMID:6999813

  13. Regional alterations of brain biogenic amines in young rats following chronic lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Dubas, T.C.; Stevenson, A.; Singhal, R.L.; Hrdina, P.D.

    1978-02-01

    An examination was made of neurochemical changes that occur in discrete brain regions of rats that have been chronically exposed to low levels of lead from birth, in order to provide further information on the involvement of brain biogenic amines in lead-induced neurotoxicity. Results indicate a relationship between exposure to lead and alterations in the brain levels of various putative neurotransmitters. However, changes in the functional activity of the neurotransmitter may not be adequately reflected in the change of its steady-state levels or may occur even in the absence of any changes in the actual concentrations. Lead may influence central neurotransmitter function by affecting one or several of the processes involved in the synthesis, release and/or disposition of biogenic amines.

  14. Chronic estrogen exposure maintains elevated levels of progesterone receptor mRNA in guinea pig hypothalamus.

    Science.gov (United States)

    Bayliss, D A; Millhorn, D E

    1991-05-01

    We performed in situ hybridization on hypothalamic sections from ovariectomized guinea pig using a cocktail of three 35S-labeled oligonucleotides complementary to mammalian progesterone receptor (PR) cDNA. PR mRNA was readily detected in hypothalamic neurons from guinea pigs pretreated with 17 beta-estradiol benzoate (E2B), but not from animals which did not receive supplemental E2B. The distribution of PR mRNA-containing cells corresponded well with previous localizations of PR in guinea pig. In contrast to earlier reports of E2B regulation of PR mRNA in rat hypothalamus, however, we found that PR mRNA remained elevated during chronic exposure to E2B (up to 10 days) in guinea pig. PMID:2072827

  15. Hepatotoxicity of ethanol in mice.

    OpenAIRE

    Goldin, R D; Wickramasinghe, S. N.

    1987-01-01

    Mice continuously exposed to ethanol vapour (for up to 19 days) developed fatty change in the liver (from 2 days onwards) and lesions resembling those of alcoholic hepatitis in man (from 5 days onwards). They also showed biochemical evidence of liver cell damage. Sera from ethanol-treated animals contained immunoglobulins that bound to the hepatocytes of ethanol-treated but not of control animals suggesting that exposure to ethanol was followed by an immunological response to a hepatocyte neo...

  16. Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

    Directory of Open Access Journals (Sweden)

    Adamcakova-Dodd Andrea

    2012-06-01

    Full Text Available Abstract Background Aluminum oxide-based nanowhiskers (AO nanowhiskers have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Methods Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH3 and AlOOH]. Male mice (C57Bl/6 J were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines, blood (total and differential cell counts, lung histopathology and pulmonary mechanics. Results Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p p  Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

  17. Associations between Chronic Community Noise Exposure and Blood Pressure at Rest and during Acute Noise and Non-Noise Stressors among Urban School Children in India

    OpenAIRE

    Bang Hyun Kim; Evans, Gary W.; Stephen J. Lepore; Bhaskar Shejwal

    2010-01-01

    The present study builds on prior research that has examined the association between children’s chronic exposure to community noise and resting blood pressure and blood pressure dysregulation during exposure to acute stressors. A novel contribution of the study is that it examines how chronic noise exposure relates to blood pressure responses during exposure to both noise and non-noise acute stressors. The acute noise stressor was recorded street noise and the non-noise stressor was mental ar...

  18. Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

    Directory of Open Access Journals (Sweden)

    B Balali-Mood

    2008-01-01

    Full Text Available The widespread use of sulphur mustard (SM as an incapacitating chemical warfare agent in the past century has proved its long-lasting toxic effects. It may also be used as a chemical terrorist agent. Therefore, all health professionals should have sufficient knowledge and be prepared for any such chemical attack. SM exerts direct toxic effects on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, immunological, haematological, digestive, and reproductive systems. SM is an alkylating agent that affects DNA synthesis, and, thus, delayed complications have been seen since the First World War. Cases of malignancies in the target organs, particularly in haematopoietic, respiratory, and digestive systems, have been reported. Important delayed respiratory complications include chronic bronchitis, bronchiectasis, frequent bronchopneumonia, and pulmonary fibrosis, all of which tend to deteriorate with time. Severe dry skin, delayed keratitis, and reduction of natural killer cells with subsequent increased risk of infections and malignancies are also among the most distressing long-term consequences of SM intoxication. However, despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Immunological and neurological dysfunction, as well as the relationship between SM exposure and mutagenicity, carcinogenicity, and teratogenicity are important fields that require further studies, particularly on Iranian veterans with chronic health effects of SM poisoning. There is also a paucity of information on the medical management of acute and delayed toxic effects of SM poisoning—a subject that greatly challenges health care specialists.

  19. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  20. Effect of head-only sub-chronic GSM exposure on spatial memory of rats

    International Nuclear Information System (INIS)

    Full text: Introduction: Low power electromagnetic fields (EMF) are suspected to produce deficit memory in rats. The study of Dubreuil et al (2003) showed that a short-term (10-15 days) exposure 'head-only' to GSM 900 MHz radio frequencies does not produce a deficit memory in adult rats. The aim of our experiment was to determine if head-only sub-chronic exposure (2 months) of rats to GSM signal for 45 min at a SAR = 1.5 W/Kg and for 15 min at 6 W/Kg induce deficit in spatial memory of rats in radial maze test. Materials and methods: Exposure system: Animals were placed in Plexiglas rockets with an individual loop antenna placed above the rat's head. Four animals were exposed at the time. Loop antennas were connected to a generator and emitted a GSM signal (900 MHz, pulsed at 217 Hz, 1/8 duty factor) 5 days / week for 8 weeks. Experimental group: 30 Sprague-Dawley male rats were randomly assigned to 5 different groups: a) 6 rats exposed 15 min at SAR = 6 W/Kg; b) 6 rats exposed 45 min at SAR = 1.5 W/g; c) 6 rats sham controls (3 for 5 min and 3 for 45 min, SAR = 0 W/Kg); d) 6 rats without any treatment and manipulation (cage control); e) 6 rats were injected (i.p) S.B.H 0.1 mg/Kg (Sigma Aldrich) as positive control group. Behavioural procedure: The radial maze protocol consists of two consecutive phases: the training task (10 days) and the test task (8 days). In the first phase, rats were trained to visit the 8 arms of the maze without returning to an arm already visited. In the second phase (8 days), a 45-min intra-trial delay was introduced after four visited arms. After the intra-delay, the rat was placed in the maze to finish the test task, which is visiting four other arms he had not visited. During the training task, exposure took place before the behavioural task. During the test task, exposure or sham-exposure took place during the intra-delay. Results and discussion: In all experiments, performance of exposed rats (1.5 and 6 W/Kg) was compared with that of

  1. Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats

    Institute of Scientific and Technical Information of China (English)

    潘宝龙

    2013-01-01

    Objective To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in SpragueDawley (SD) rats.Methods Thirty-two male SD rats were randomly and equally divided into 4 groups:control group and high-,middle-,and low-dose exposure groups.The rats in high-,middle-,and low-dose expo-

  2. SB242084, flumazenil, and CRA1000 block ethanol withdrawal–induced anxiety in rats

    OpenAIRE

    KNAPP, DARIN J.; Overstreet, David H.; Moy, Sheryl S.; Breese, George R.

    2004-01-01

    Anxiety-like behaviors are integral features of withdrawal from chronic ethanol exposure. In the experiments in the current study, we tested the hypothesis that anxiety can be regulated independently of other withdrawal signs and thus may be responsive to selective pharmacological agents. For 17 days, rats were fed ethanol (8–12 g/kg/day) in a liquid diet. Between 5 and 6 h after cessation of ethanol treatment, rats were tested in either the social interaction or plus-maze test of anxiety-lik...

  3. Ethanol and oxidative stress.

    Science.gov (United States)

    Sun, A Y; Ingelman-Sundberg, M; Neve, E; Matsumoto, H; Nishitani, Y; Minowa, Y; Fukui, Y; Bailey, S M; Patel, V B; Cunningham, C C; Zima, T; Fialova, L; Mikulikova, L; Popov, P; Malbohan, I; Janebova, M; Nespor, K; Sun, G Y

    2001-05-01

    This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Albert Y. Sun. The presentations were (1) Ethanol-inducible cytochrome P-4502E1 in alcoholic liver disease, by Magnus Ingelman-Sundberg and Etienne Neve; (2) Regulation of NF-kappaB by ethanol, by H. Matsumoto, Y. Nishitani, Y. Minowa, and Y. Fukui; (3) Chronic ethanol consumption increases concentration of oxidized proteins in rat liver, by Shannon M. Bailey, Vinood B. Patel, and Carol C. Cunningham; (4) Antiphospholipids antibodies and oxidized modified low-density lipoprotein in chronic alcoholic patients, by Tomas Zima, Lenka Fialova, Ludmila Mikulikova, Ptr Popov, Ivan Malbohan, Marta Janebova, and Karel Nespor; and (5) Amelioration of ethanol-induced damage by polyphenols, by Albert Y. Sun and Grace Y. Sun. PMID:11391077

  4. Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida

    International Nuclear Information System (INIS)

    Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms

  5. Effects of depleted uranium chronic exposure on detoxification systems in vivo and in vitro

    International Nuclear Information System (INIS)

    Uranium (U) is a heavy metal naturally presents in the environment. The aim of this work is to study effects of a U exposure on organs involved in the detoxification: the kidney and the liver (and notably the xenobiotics metabolizing enzymes (XME)). In order to mimic population chronic exposure, rats were contaminated during 9 months through the drinking water (40 mg/L). In vivo results show that U, in our experimental conditions, does not induce neither nephrotoxicity nor sensitivity to increase a renal toxicity induced by gentamicin. In the liver, U provokes impairments on the XME gene expression, particularly CYP3A. Nevertheless, paracetamole metabolism is modified only if it is administrated at a hepatotoxic dose. The in vitro results suggest an indirect effect of uranium on the XME, probably dependant of body adaptation mechanisms. Besides, in vitro studies were underline cytotoxic properties of U as well as the localisation of its soluble and/or participated forms in cytoplasmic and nuclear compartment. (author)

  6. Chronic exposure to gamma radiation of wild populations of meadow voles (Microtus pennsylvanicus)

    International Nuclear Information System (INIS)

    Free-ranging, wild meadow voles (Microtus pennsylvanicus) were exposed to gamma radiation from a 137Cs irradiator in a series of experiments conducted on six 1-ha meadows within a mixed deciduous forest in Manitoba, Canada. Over a period of 1-1.5 years in each of three experiments, vole populations were monitored with capture-mark-release techniques at nominal exposure rates of 200x, 9000x and 40,000x background. No effects on population or individual characteristics were detected up to the highest exposure rate (81 mGy/d). At this level, third generation voles were monitored up to a lifetime dose of about 5.7 Gy, at a measured dose rate of 44 mGy/d. Smaller numbers of overwintered animals survived and reproduced normally at doses up to 10 Gy. These results are discussed in terms of low-LET, external chronic radiation effects on rodents in the laboratory and the field, relative to current views on appropriate benchmarks for the protection of biota

  7. Effects of long-term chronic exposure to radionuclides in plant populations

    International Nuclear Information System (INIS)

    The results of field studies carried out on different plant species (winter rye and wheat, spring barley, oats, Scots pine, wild vetch, crested hairgrass) in various radioecological situations (nuclear weapon testing, the Chernobyl accident, uranium and radium processing) to investigate the effects of long-term chronic exposure to radionuclides are discussed. Plant populations growing in areas with relatively low levels of pollution are characterized by an increased level of both cytogenetic disturbances and genetic diversity. Although ionizing radiation causes primary damage at the molecular level, there are emergent effects at the level of populations, non-predictable from the knowledge of elementary mechanisms of cellular effects formation. Accumulation of cellular alterations may afterward influence biological parameters important for populations such as health and reproduction. Presented data provide evidence that in plant populations inhabiting heavily contaminated territories cytogenetic damage could be accompanied by a decrease in reproductive capacity. However, in less contaminated sites, because of the scarcity of data available, a steady relationship between cytogenetic effects and reproductive capacity was not revealed. Under radioactive contamination of the plant's environment, a population's resistance to exposure may increase. However, there are radioecological situations where an enhanced radioresistance has not evolved or has not persisted

  8. Nuclear toxicology file: ecological consequences of a chronic exposure to uranium

    International Nuclear Information System (INIS)

    This article presents the thought process and the current developments, based on the experimental acquisition of the answers of the alive organisms to the chronic low dose exposures of natural uranium in fresh water, to identify the consequences of this exposure on the populations composing the ecosystems. The results acquired on the zebra fish (Danio rerio) show an impact on the first steps of development. We note a delay of hatching upon 40 % from 20 μg/l of uranium. This delay comes along with a decrease of the size and with a reduction of the growth of larvas as well as with an increase of their mortality for higher uranium concentration. For adults exposed to uranium a decrease of reproduction success is observed from a concentration of 20μg/l. The consequences in term of fertility (total number of laid roes) are drastic, with a reduction of a factor 2 and 60, for the organisms exposed respectively to 20 and 250 μg/l of uranium. A study was also made on several generations (populations of benthic invertebrates), it suggests an adaptation (genetic selection) but created a bigger fragility to a new environment even identical to their environment of origin with notably a decrease of the reproduction. (N.C.)

  9. Response of tibialis anterior tendon to a chronic exposure of stretch-shortening cycles: age effects

    Directory of Open Access Journals (Sweden)

    Baker Brent B

    2009-06-01

    Full Text Available Abstract Background The purpose of the current study was to investigate the effects of aging on tendon response to repetitive exposures of stretch-shortening cycles (SSC's. Methods The left hind limb from young (3 mo, N = 4 and old (30 mo, N = 9 male Fisher 344 × Brown Norway rats were exposed to 80 maximal SSCs (60 deg/s, 50 deg range of motion 3x/week for 4.5 weeks in vivo. After the last exposure, tendons from the tibialis anterior muscle were isolated, stored at -80°C, and then tested using a micro-mechanical testing machine. Deformation of each tendon was evaluated using both relative grip-to-grip displacements and reference marks via a video system. Results At failure, the young control tendons had higher strain magnitude than the young exposed (p Conclusion The chronic protocol enhanced the elastic stiffness of young tendon and the loads in both the young and old tendons. The old exposed tendons were found to exhibit higher load capacity than their younger counterparts, which differed from our initial hypothesis.

  10. [MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE].

    Science.gov (United States)

    Byelinska, I V; Lynchak, O V; Tsyvinska, S M; Rybalchenko, V K

    2015-01-01

    The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug PMID:26552308

  11. Effects of Sub-chronic Aluminum Exposure on Renal Structure in Rats

    Institute of Scientific and Technical Information of China (English)

    Li Yan-fei; Liu Jian-yu; Cao Zheng

    2015-01-01

    To investigate the effects of aluminum (Al) exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 (control group, GC), 64.18 (low-dose group, GL), 128.36 (middle-dose group, GM), and 256.72 (high-dose group, GH) mg• kg-1 BW AlCl3 in drinking water for 120 days. The body weight of different rats was recorded, the kidney pathologic structure and the ultrastructure were observed. The results showed that the body weight of different rats was markedly lower in Al-treated rats than those in GC (P<0.05;P<0.01). After masson staining, the collagen was deposited in the renal interstitium and aggravated with Al dose increases in Al-treated rats. Under electron microscope, the infolding of the plasma membrane was slight swollen, the mitochondrion was abundant with different sizes, the mitochondrion cristae was fused, the microvillus was swollen and fused in GH. Our findings indicated that sub-chronic Al exposure slowed the weight of rats and caused the kidney pathologic damage in rats.

  12. The reproductive effects in rats after chronic oral exposure to low-dose depleted uranium

    International Nuclear Information System (INIS)

    This two-generation study evaluated the effects of depleted uranium (DU) on reproduction in rats. Across two generations, Wistar rats (30/sex/group) were maintained on feed containing DU at dose levels of 0 (control group), 4 (DU4 group), or 40 (DU40 group) mg kg-1 day-1 for 4 months prior to mating. After 4 months of exposure, the pregnancy rate, normal labour rate, and survival rate of offspring produced by F1 rats were all significantly decreased as compared to the control group, and especially in the DU40 group, these parameters fell by half to two-thirds, while no adverse effects were evident in F0 rats. The uranium content in the testes and ovaries of F1 rats in the DU4 and DU40 groups was significantly higher than that found in F0 rats. The levels of sex hormone in the serum were disorder in both generations. The enzymes related to spermiogenesis were also significantly different between generations, and the damage was more severe in F1 rats. In conclusion, the reproductive effects in F0 rats were slight after chronic oral exposure to DU, while the effects were obvious in F1 rats. (author)

  13. Pulmonary and hepatic injury after sub-chronic exposure to sublethal doses of microcystin-LR.

    Science.gov (United States)

    Carvalho, Giovanna Marcella Cavalcante; Oliveira, Vinícius Rosa; Casquilho, Natália Vasconcelos; Araujo, Andressa Cristine Pereira; Soares, Raquel Moraes; Azevedo, Sandra Maria F O; Pires, Karla Maria Pereira; Valença, Samuel Santos; Zin, Walter Araujo

    2016-03-15

    We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 μL, CTRL) or different doses of MCLR (5 μg/kg, TOX5), 10 μg/kg (TOX10), 15 μg/kg (TOX15) and 20 μg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group. PMID:26844922

  14. Chronic exposure to low-levels of lead in the rat: biochemical and behavioural changes

    International Nuclear Information System (INIS)

    The prevalence of lead in the environment is a cause of continuing toxicology concern and there have been numerous human and animal studies to examine more thoroughly the possible consequences of exposure to this ecotoxicant. Because lead is highly toxic to the developing central nervous system, increasing concern over the rise in the lead content in the environment has been expressed. These concerns seem appropriate since more recent clinical studies have shown that prolonged exposure of children to so called 'subclinical' concentrations of lead may be associated with behavioural disorders, learning disabilities and mental retardation. Moreover, animal studies have shown that chronic perinatal low-level lead exposure elicits alterations in both learned and spontaneous behavioural patterns in the absence of typical outward signs of lead-induced neurological toxicity. No study however could relate behavioural changes to specific alterations in neurochemisty. The aim of this study was therefore to expose rats, in different stages of their development, to low-levels of lead in order to induce behavioural disorders and correlate latter with possible neurochemical changes. In accordance with the general aims of the study, the structuring of the thesis is as follows: (a) a discussion of the neurotransmitters in the brain in order to describe the different systems which have been investigated; (b) a review of appropriate literature regarding the kinetics, toxodynamics and neurotoxicity of lead and (c) a summary of the methods employed in the study. The following results are presented: (d) the effects of lead treatment on physical development of the rats; (e) the induction of behavioural supersensitivity and (f) the effects lead has on central receptors

  15. Immunological changes of chronic oral exposure to depleted uranium in mice.

    Science.gov (United States)

    Hao, Yuhui; Ren, Jiong; Liu, Jing; Yang, Zhangyou; Liu, Cong; Li, Rong; Su, Yongping

    2013-07-01

    Direct ingestion of contaminated soil by depleted uranium (DU) might lead to internal exposure to DU by local populations through hand contamination. The purpose of this study was to assess the immunological changes of long-term exposure to various doses of DU in mice. Three-week-old Kunming mice were divided into the following 4 groups based on the various feeding doses (containing DU): 0 (control group), 3 (DU3 group), 30 (DU30 group), and 300 mg/kg feed (DU300 group). After 4 months of exposure, in the DU300 group, the innate immune function decreased, manifesting as decreased secretion of nitric oxide, interleukin (IL)-1β, IL-18, and tumour necrosis factor (TNF)-α in the peritoneal macrophages, as well as reduced cytotoxicity of the splenic natural killer cells. Moreover, the cellular and humoral immune functions were abnormal, as manifested by decreased proliferation of the splenic T cells, proportion of the cluster of differentiation (CD) 3(+) cells, ratio of CD4(+)/CD8(+) cells and delayed-type hypersensitivity, and increased proliferation of the splenic B cells, total serum immunoglobin (Ig) G and IgE, and proportion of splenic mIgM(+)mIgD(+) cells. Through stimulation, the secretion levels of interferon (IFN)-γ and TNF-α in the splenic cells were reduced, and the levels of IL-4 and IL-10 were increased. By comparison, in the DU30 and DU3 groups, the effects were either minor or indiscernible. In conclusions, chronic intake of higher doses of DU (300 mg/kg) had a significant impact on the immune function, most likely due to an imbalance in T helper (Th) 1 and Th2 cytokines. PMID:23659960

  16. Quantitative Neuropathology Associated with Chronic Manganese Exposure in South African Mine Workers

    Science.gov (United States)

    Gonzalez-Cuyar, Luis F.; Nelson, Gill; Criswell, Susan R.; Ho, Pokuan; Lonzanida, Jaymes A.; Checkoway, Harvey; Seixas, Noah; Gelman, Benjamin B.; Evanoff, Bradley A.; Murray, Jill; Zhang, Jing; Racette, Brad A.

    2014-01-01

    Manganese (Mn) is a common neurotoxicant associated with a clinical syndrome that includes signs and symptoms referable to the basal ganglia. Despite many advances in understanding the pathophysiology of Mn neurotoxicity in humans, with molecular and structural imaging techniques, only a few case reports describe the associated pathological findings, and all are in symptomatic subjects exposed to relatively high-level Mn. We performed an exploratory, neurohistopathological study to investigate the changes in the corpus striatum (caudate nucleus, putamen, and globus pallidus) associated with chronic low-level Mn exposure in South African Mn mine workers. Immunohistochemical techniques were used to quantify cell density of neuronal and glial components of the corpus striatum in eight South African Mn mine workers without clinical evidence of a movement disorder and eight age-race-gender matched, non-Mn mine workers. There was higher mean microglia density in Mn mine workers than non-Mn mine workers in the globus pallidus external and internal segments [GPe: 1.33 and 0.87 cells per HPF, respectively (p=0.064); GPi: 1.37 and 0.99 cells per HPF, respectively (p=0.250)]. The number of years worked in the Mn mines was significantly correlated with microglial density in the GPi (Spearman's rho 0.886; p=0.019). The ratio of astrocytes to microglia in each brain region was lower in the Mn mine workers than the non-Mn mine workers in the caudate (7.80 and 14.68; p=0.025), putamen (7.35 and 11.11; p=0.117), GPe (10.60 and 16.10; p=0.091) and GPi (9.56 and 12.42; p=0.376). Future studies incorporating more detailed occupational exposures in a larger sample of Mn mine workers will be needed to demonstrate an etiologic relationship between Mn exposure and these pathological findings. PMID:24374477

  17. Effects of chronic exposure to ionising radiation in the Pacific oyster Crassostrea gigas

    International Nuclear Information System (INIS)

    The Cotentin peninsula (Normandy, France) hosts nuclear industry facilities which operate with controlled discharges of radionuclides in the marine environment. Compared to natural radioactivity, the increase by artificial radionuclides is small but constant. As a consequence, marine species are chronically exposed to low additional doses of ionizing radiation (IR). The effects of chronic exposure to radionuclides were investigated in early stages of development of the Japanese oyster Crassostrea gigas. On the basis of literature, mollusks are expected to be particularly resistant to acute IR (UNSCEAR, 1996. Sources and effects of ionizing radiation. Report to the General Assembly, with Scientific Annex. 86 p). Two different chronic exposure conditions consisted in external (137Cs) and internal (241Am) irradiation for two weeks. Biological endpoints were analyzed in parallel at both the integrated (growth) and molecular (target stress gene expression) levels. To identify potential biological targets of IR, oysters were first exposed to very high dose rates and radionuclide activities with the perspective to reduce the levels and to derive dose-response curves. Although the initial exposure levels (137Cs 30 000 μGy.h-1; 241Am 57 000 Bq.L-1) were many orders of magnitude higher than those encountered in the natural environment, no significant change in the measured parameters was observed. This result was surprising because data from the literature showed that exposure of mussel Mytilus edulis to 3H at lower doses rates (10-100 μGy.h-1) induced DNA damage in hemocytes (Jha et al., 2005. Impact of low doses of tritium on the marine mussel, Mytilus edulis: Genotoxic effects and tissue-specific bioconcentration. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 586, 47-57). To understand this apparent discrepancy between those two filtering bivalves, a new experiment was performed to compare the response of oyster exposed to 3H in the same condition

  18. Effects of chronic exposure to ionising radiation in the Pacific oyster Crassostrea gigas

    Energy Technology Data Exchange (ETDEWEB)

    Fievet, B.; Devos, A.; Voiseux, C.; Leconte-Pradines, C. [Institut de Radioprotection et de Surete' Nucleaire (France); Dallas, L.; Jha, A. [University of Plymouth (United Kingdom)

    2014-07-01

    The Cotentin peninsula (Normandy, France) hosts nuclear industry facilities which operate with controlled discharges of radionuclides in the marine environment. Compared to natural radioactivity, the increase by artificial radionuclides is small but constant. As a consequence, marine species are chronically exposed to low additional doses of ionizing radiation (IR). The effects of chronic exposure to radionuclides were investigated in early stages of development of the Japanese oyster Crassostrea gigas. On the basis of literature, mollusks are expected to be particularly resistant to acute IR (UNSCEAR, 1996. Sources and effects of ionizing radiation. Report to the General Assembly, with Scientific Annex. 86 p). Two different chronic exposure conditions consisted in external ({sup 137}Cs) and internal ({sup 241}Am) irradiation for two weeks. Biological endpoints were analyzed in parallel at both the integrated (growth) and molecular (target stress gene expression) levels. To identify potential biological targets of IR, oysters were first exposed to very high dose rates and radionuclide activities with the perspective to reduce the levels and to derive dose-response curves. Although the initial exposure levels ({sup 137}Cs 30 000 μGy.h{sup -1}; {sup 241}Am 57 000 Bq.L{sup -1}) were many orders of magnitude higher than those encountered in the natural environment, no significant change in the measured parameters was observed. This result was surprising because data from the literature showed that exposure of mussel Mytilus edulis to {sup 3}H at lower doses rates (10-100 μGy.h{sup -1}) induced DNA damage in hemocytes (Jha et al., 2005. Impact of low doses of tritium on the marine mussel, Mytilus edulis: Genotoxic effects and tissue-specific bioconcentration. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 586, 47-57). To understand this apparent discrepancy between those two filtering bivalves, a new experiment was performed to compare the response

  19. HEALTH RISKS FROM CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER: FINDINGS FROM THE CLINICAL INVESTIGATIONS DATA IN INNER MONGOLIA, CHINA

    Science.gov (United States)

    Prior studies have reported a large number of arsenicism cases in the Mongolia Autonomous Region of China due to drinking arsenic-contaminated water with concentrations up to 1.8 mg/L. However, the endemic health risks from chronic exposure to arsenic in this population have not...

  20. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    International Nuclear Information System (INIS)

    Stress and ethanol are both, independently, important cardiovascular risk factors. To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure

  1. Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via α2-Adrenoceptor

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Rafaela de Fátima Ferreira [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Taipeiro, Elane de Fátima [Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Queiroz, Regina Helena Costa [Departamento de Análise Clínica - Toxicológica e Ciência de Alimentos - Faculdade de Ciências Farmacêuticas - USP, São Paulo, SP (Brazil); Chies, Agnaldo Bruno [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil); Laboratório de Farmacologia - Faculdade de Medicina de Marília - FAMEMA, SP (Brazil); Cordellini, Sandra, E-mail: cordelli@ibb.unesp.br [Departamento de Farmacologia - Instituto de Biociências - Universidade Estadual Paulista - UNESP - São Paulo, SP (Brazil)

    2014-03-15

    Stress and ethanol are both, independently, important cardiovascular risk factors. To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure.

  2. Neurosteroid effects on sensitivity to ethanol

    Directory of Open Access Journals (Sweden)

    Christa M Helms

    2012-01-01

    Full Text Available Harrison and Simmonds (1984 provided the first clear evidence that neuroactive steroids act at specific neurotransmitter receptors, investigating the potentiation of muscimol-induced GABAA responses by alphaxalone (3α-hydroxy 5α -pregnane l l,20-dione in cortical slices. Within 2 years, a progesterone metabolite (3α-hydroxy-5α-pregnan-20-one, 3α,5α-THP, allopregnanolone and a deoxycorticosterone metabolite (3α,21-dihydroxy-5α-pregnan-20-one, 3α,5α-THDOC, tetrahydrodeoxycorticosterone, THDOC were shown to be positive modulators of GABAA receptors (Majewska et al., 1986. That same year, publications showed that ethanol has direct action at GABAA receptors (Allan and Harris, 1986, Suzdak et al., 1986. Thus, the GABAA receptor complex was identified as a membrane-bound target providing a pharmacological basis for shared sensitivity between neurosteroids and ethanol. The common behavioral effects of ethanol and neuroactive steroids were compared directly using drug discrimination procedures (Ator et al., 1993. The N-methyl-D-aspartate (NMDA receptor complex, a membrane-bound ionophore important for excitatory glutamate neurotransmission, was shown to be antagonized by low concentrations of ethanol (Lovinger et al., 1989. Since data were emerging for neurosteroid activity at NMDA receptors (Wu et al., 1991, the stage was set for the suggestion that neurosteroids, and physiological states that alter circulating neuroactive steroids, could affect sensitivity to alcohol (Grant et al., 1997. The unique interface of ethanol and neurosteroids encompasses molecular, cellular, physiological and behavioral processes. This review will highlight a variety of mechanisms by which neurosteroids affect sensitivity to ethanol, including metabolic pathways, physiological states associated with activity of the hypothalamic-pituitary adrenal (HPA and hypothalamic-pituitary-gonadal (HPG axes, and the effects of chronic exposure to ethanol, in addition to

  3. Evaluation of Acute and Sub-chronic Toxicities of Aqueous Ethanol Root Extract of Raphia hookeri Palmaceae on Swiss Albino Rats

    Directory of Open Access Journals (Sweden)

    G.O. Mbaka

    2014-08-01

    Full Text Available This study evaluated the acute and sub-chronic toxicities of treatment with aqueous ethanol root extract of Raphia hookri (Palmaceae on rats. In acute toxicity study, the root extract in a graded doses of 125-2000 mg/kg bwt administered Intra-Peritoneal (IP produced dose dependent mortality with median acute toxicity (LD50 of approximately 562.3 mg/kg bwt. The animals fed with the extract by gavages tolerated up to 4000 mg/kg body weight (bwt with no sign of physical/behavioural changes hence 1/20th of the dose (200 mg/kg was used as the highest therapeutic dose. In sub-chronic toxicity study, significant increase (p0.05 decrease in Red Blood Cell (RBC count and haemoglobin (Hb level while White Blood Cell (WBC showed increase. In tissue analysis, the extract caused marked deleterious effect on the testes leading to drastic reduction in sperm cells whereas tissues of liver, kidney and heart however showed normal appearance.

  4. Review of the chronic exposure pathways models in MACCS [MELCOR Accident Consequence Code System] and several other well-known probabilistic risk assessment models

    International Nuclear Information System (INIS)

    The purpose of this report is to document the results of the work performed by the author in connection with the following task, performed for US Nuclear Regulatory Commission, (USNRC) Office of Nuclear Regulatory Research, Division of Systems Research: MACCS Chronic Exposure Pathway Models: Review the chronic exposure pathway models implemented in the MELCOR Accident Consequence Code System (MACCS) and compare those models to the chronic exposure pathway models implemented in similar codes developed in countries that are members of the OECD. The chronic exposures concerned are via: the terrestrial food pathways, the water pathways, the long-term groundshine pathway, and the inhalation of resuspended radionuclides pathway. The USNRC has indicated during discussions of the task that the major effort should be spent on the terrestrial food pathways. There is one chapter for each of the categories of chronic exposure pathways listed above

  5. Tissue-specific Bio-accumulation of Metals in Fish during Chronic Waterborne and Dietary Exposures

    Directory of Open Access Journals (Sweden)

    M. Javed

    2012-10-01

    Full Text Available Juvenile (120-day three fish species viz. Catla catla, Labeo rohita and Cirrhina mrigala were exposed to chronic sub-lethal concentrations (1/3rd of LC50/LD50 of waterborne and dietary copper (Cu, cadmium (Cd, zinc (Zn, nickel (Ni and cobalt (Co, separately, in glass aquaria under constant water temperature (29oC, pH (7.5 and hardness (225 mgL-1 for 12 weeks. Waterborne and dietary exposures caused significantly variable accumulation of metals in three fish species that followed Zn>Ni>Cd>Co>Cu. Fish liver showed significantly higher tendency to accumulate Cu (69.64±25.35 µg g-1, Cd (68.93±21.65 µg g-1, Zn (91.46±29.53 µg g-1, Ni (74.64±18.61 µg g-1 and Co (22.65±20.56 µg g-1, followed by that of kidney and gills, with significant differences while muscle and bones exhibited significantly least tendency to accumulate all metals. Labeo rohita (31.63±2.43 µg g-1 and C. mrigala (31.43±13.70 µg g-1 exhibited significantly higher ability to amass metals than that of C. catla (27.96±10.28 µg g-1. Waterborne exposure caused significantly higher accumulation of metals in fish liver (72.69±27.91 µg g-1, followed by that in kidney, gills, skin, muscle, fins and bones with the average concentrations of 45.14±18.70, 39.47±21.13, 30.81±12.64, 22.65±17.34, 22.23±11.74 and 12.14±6.25 µg g-1, respectively. Dietary exposure resulted into significant escalation of metals in fish liver (58.23±32.44 µg g-1 while it was lowest in bones. Waterborne exposure caused significantly higher accumulation of all metals in fish body than that of dietary treatments.

  6. Dust exposure and chronic respiratory symptoms among coffee curing workers in Kilimanjaro: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Sakwari Gloria

    2011-11-01

    Full Text Available Abstract Background Coffee processing causes organic dust exposure which may lead to development of respiratory symptoms. Previous studies have mainly focused on workers involved in roasting coffee in importing countries. This study was carried out to determine total dust exposure and respiratory health of workers in Tanzanian primary coffee-processing factories. Methods A cross sectional study was conducted among 79 workers in two coffee factories, and among 73 control workers in a beverage factory. Personal samples of total dust (n = 45 from the coffee factories and n = 19 from the control factory were collected throughout the working shift from the breathing zone of the workers. A questionnaire with modified questions from the American Thoracic Society questionnaire was used to assess chronic respiratory symptoms. Differences between groups were tested by using independent t-tests and Chi square tests. Poisson Regression Model was used to estimate prevalence ratio, adjusting for age, smoking, presence of previous lung diseases and years worked in dusty factories. Results All participants were male. The coffee workers had a mean age of 40 years and were older than the controls (31 years. Personal total dust exposure in the coffee factories were significantly higher than in the control factory (geometric mean (GM 1.23 mg/m3, geometric standard deviation (GSD (0.8 vs. 0.21(2.4 mg/m3. Coffee workers had significantly higher prevalence than controls for cough with sputum (23% vs. 10%; Prevalence ratio (PR; 2.5, 95% CI 1.0 - 5.9 and chest tightness (27% vs. 13%; PR; 2.4, 95% CI 1.1 - 5.2. The prevalence of morning cough, cough with and without sputum for 4 days or more in a week was also higher among coffee workers than among controls. However, these differences were not statistically significant. Conclusion Workers exposed to coffee dust reported more respiratory symptoms than did the controls. This might relate to their exposure to coffee dust

  7. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    Science.gov (United States)

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  8. Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

    Institute of Scientific and Technical Information of China (English)

    HENG CHUAN XIA; FENG LI; ZHEN LI; ZU CHUAN ZHANG

    2003-01-01

    It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT)mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times.After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITCconjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice.

  9. Ethanol-induced loss of brain cyclic AMP binding proteins: correlation with growth suppression

    International Nuclear Information System (INIS)

    Brain hypoplasia secondary to maternal ethanol consumption is a common fetal defect observed in all models of fetal alcohol syndrome. The molecular mechanism by which ethanol inhibits growth is unknown but has been hypothesized to involve ethanol-induced changes in the activity of cyclic-AMP stimulated protein kinase. Acute and chronic alcohol exposure elevate cyclic AMP level in many tissues, including brain. This increase in cyclic AMP should increase the phosphorylating activity of kinase by increasing the amount of dissociated (active) kinase catalytic subunit. In 7-day embryonic chick brains, ethanol-induced growth suppression was correlated with increased brain cyclic AMP content but neither basal nor cyclic AMP stimulated kinase catalytic activity was increased. However, the levels of cyclic AMP binding protein (kinase regulatory subunit) were significantly lowered by ethanol exposure. Measured as either 3H cyclic AMP binding or as 8-azido cyclic AM32P labeling, ethanol-exposed brains had significantly less cyclic AMP binding activity (51 +/- 14 versus 29 +/- 10 units/μg protein for 8-azido cyclic AMP binding). These findings suggest that ethanol's effect on kinase activity may involve more than ethanol-induced activation of adenylate cyclase

  10. Autophagy is a protective response to ethanol neurotoxicity

    OpenAIRE

    Chen, Gang; Ke, Zunji; Xu, Mei; Liao, Mingjun; Wang, Xin; Qi, Yuanlin; Zhang,Tao; Frank, Jacqueline A.; Bower, Kimberly A.; Shi, Xianglin; Luo, Jia

    2012-01-01

    Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. The mechanisms underlying ethanol-induced neurodegeneration are complex. Ethanol exposure produces reactive oxygen species (ROS) which cause oxidative stress in the brain. We hypothesized that ethanol would activate autophagy to alleviate oxidative stress and neurotoxicity. Our results indicated that ethanol increased the level of the autophagic marker Map1lc3-II (LC3-II...

  11. Effects of Acute and Chronic Heavy Metal (Cu, Cd, and Zn Exposure on Sea Cucumbers (Apostichopus japonicus

    Directory of Open Access Journals (Sweden)

    Li Li

    2016-01-01

    Full Text Available Acute and chronic toxicity tests were conducted with sea cucumber (Apostichopus japonicus exposed to heavy metals. Acute toxicity values (96 h LC50 were 2.697, 0.133, and 1.574 mg L−1 for Zn, Cu, and Cd, respectively, and were ranked in order of toxicity: Cu > Cd > Zn. Under chronic metal exposure the specific growth rates of sea cucumbers decreased with the increase of metal concentration for all the three metals. After acute metal exposure, the oxygen consumption rate (OCR decreased. The OCRs in all groups were significantly different than control (P muscle > intestine in natural sea water. After chronic Zn, Cu, and Cd exposure, the change pattern of HK and PK in respiratory tree, muscle, and intestine varied slightly. However, the activity of the enzyme showed a general trend of increase and then decrease and the higher the exposure concentration was, the earlier the highest point of enzyme activity was obtained.

  12. The chronic toxicity of bisphenol A to Caenorhabditis elegans after long-term exposure at environmentally relevant concentrations.

    Science.gov (United States)

    Zhou, Dong; Yang, Jie; Li, Hui; Cui, Changzheng; Yu, Yunjiang; Liu, Yongdi; Lin, Kuangfei

    2016-07-01

    To investigate biological effects of bisphenol A (BPA) over the long term, the model animal Caenorhabditis elegans was used to conduct the chronic exposure. C. elegans were exposed to BPA (0.0001-10 μM) from L4 larvae to day-10 adult in the present chronic toxicity assay system. Multiple endpoints at the physiological (growth, locomotion behaviors and lifespan), biochemical (lipofuscin accumulation), molecular (stress-related genes expressions), and population (population size) levels were examined. At the physiological level, BPA exposure induced significant negative effects on the indicators. Among the endpoints, head thrash was most sensitive and the detection limit was 0.001 μM. At the biochemical level, BPA exposure induced no significant effects on lipofuscin accumulation. At the molecular level, BPA induced strong stress responses in vivo. At the population level, the population size was significantly decreased in the treatment groups from 0.1 to 10 μM. Compared to the previous short-term toxicity evaluation, long-term exposure to BPA induced a more obvious response at the same concentration, and the phenomenon might be due to cumulative toxic effects. By the Pearson correlation analyses, cep-1 was speculated to act as an important role in BPA-induced chronic toxicity on C. elegans. PMID:27085314

  13. Ways of pharmacological prophylaxis of stochastic and deterministic effects of chronical radiation exposure

    International Nuclear Information System (INIS)

    The prophylactics of late effects of exposure is the actual medico-social problem, because now there are large groups of persons who were exposed during occupational contact and living on territories contaminated by radionuclides. Most probable consequences of external and internal chronic influence of radiation may be the increase of malignant tumour frequency, the development of secondary myelo- and immuno-depressions, the earlier forming of sclerous and destructive processes, and the acceleration of senescence. The role of damages in immune system was not yet understood in pathogenesis of the late effects of radiation, but there are evidences that the decreasing of the immunologic supervision in period of forming the consequences of radiation influence enables to realize the cancerogenic effect of radiation. The purposes of this investigation are to decrease the frequency or to prevent the development of radiation consequences dangerous for health and life by using the method of modification of radiogenic damages in hemopoietic and immune systems by applying the pharmacological preparations with immunomodulating effects. The investigation tasks include: the study of modifying influence of pharmacological substances with different mechanisms of effect: myelopid (immunomodulating, and regulatory), β-carotin, Calendula officinalis (immunomodulating, and antioxidant), lipamid (detoxicating); the separate or complex applications of these substances; and the development of the optimum medico-prophylactic schemes. The advantages of these indicated preparations in comparison with the known (T-activin, thymogen, cytokines, etc.) are the absence of contraindications and the possibility to use per os. (author)

  14. Metamorphosis of two amphibian species after chronic cadmium exposure in outdoor aquatic mesocosms

    Science.gov (United States)

    James, S.M.; Little, E.E.; Semlitsch, R.D.

    2005-01-01

    Amphibian larvae at contaminated sites may experience an alteration of metamorphic traits and survival compared to amphibians in uncontaminated conditions. Effects of chronic cadmium (Cd) exposure on the metamorphosis of American toads (Bufo americanus) and southern leopard frogs (Rana sphenocephala) were determined. The two species were reared separately from shortly after hatching through metamorphosis in outdoor mesocosms (1,325-L polyethylene cattle tanks) that simulated natural ponds and enhanced environmental realism relative to the laboratory. Both species exhibited a decrease in survival with increasing initial nominal aqueous Cd concentration. Cadmium treatment did not influence mass at metamorphosis for either species when survival was included as a covariate, but increased the age at metamorphosis for the American toads. The whole body Cd content of metamorphs increased with aqueous Cd treatment level for both species, and the American toads tended to possess more elevated residues. Cadmium quickly partitioned out of the water column and accumulated in and altered the abundance of the tadpoles' diet. Cadmium-contaminated sites may produce fewer metamorphs, and those that survive will metamorphose later and contain Cd. Interspecific differences in the response variables illustrate the importance of testing multiple species when assessing risk. ?? 2005 SETAC.

  15. Modelling the propagation of effects of chronic exposure to ionising radiation from individuals to populations

    Energy Technology Data Exchange (ETDEWEB)

    Alonzo, F. [Laboratory of Environmental Modelling, DEI/SECRE/LME, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache, Building 159, BP3, 13115 St-Paul-lez-Durance Cedex (France); Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France)], E-mail: frederic.alonzo@irsn.fr; Hertel-Aas, T. [Department of Plant and Environmental Sciences, P.O. Box 5003, Norwegian University of Life Sciences, 1432 Aas (Norway); Gilek, M. [School of Life Sciences, Soedertoern University College, 14189 Huddinge (Sweden); Gilbin, R. [Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France); Oughton, D.H. [Department of Plant and Environmental Sciences, P.O. Box 5003, Norwegian University of Life Sciences, 1432 Aas (Norway); Garnier-Laplace, J. [Laboratory of Radioecology and Ecotoxicology, DEI/SECRE/LRE, Institute of Radioprotection and Nuclear Safety (IRSN), Cadarache Building 186, BP3, 13115 St-Paul-lez-Durance Cedex (France)

    2008-09-15

    This study evaluated the potential effect of ionising radiation on population growth using simple population models and parameter values derived from chronic exposure experiments in two invertebrate species with contrasting life-history strategies. In the earthworm Eisenia fetida, models predicted increasing delay in population growth with increasing gamma dose rate (up to 0.6 generation times at 11 mGy h{sup -1}). Population extinction was predicted at 43 mGy h{sup -1}. In the microcrustacean Daphnia magna, models predicted increasing delay in population growth with increasing alpha dose rate (up to 0.8 generation times at 15.0 mGy h{sup -1}), only after two successive generations were exposed. The study examined population effects of changes in different individual endpoints (including survival, number of offspring produced and time to first reproduction). Models showed that the two species did not respond equally to equivalent levels of change, the fast growing daphnids being more susceptible to reduction in fecundity or delay in reproduction than the slow growing earthworms. This suggested that susceptibility of a population to ionising radiation cannot be considered independent of the species' life history.

  16. HIGH-Resolution CT in Chronic Pulmonary Changes after Mustard Gas Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bagheri, M.H.; Mostafavi, S.H. [Shiraz Univ. of Medical Siences (Iran, Islamic Republic of). Dept. of Radiology; Hosseini, S.K. [Shiraz Univ. of Medical Siences (Iran, Islamic Republic of). Dept. of Internal Medicine; Alavi, S.A. [Medical Center for Chemical Warfare Victims Foundation, Shiraz (Iran, Islamic Republic of)

    2003-05-01

    Purpose: To identify the findings of high-resolution CT (HRCT) of the lung in patients with previous sulfur mustard gas exposure, and to correlate these findings with clinical and chest X-ray (CXR) results. Material and Methods: 50 consecutive patients were studied prospectively. The clinical data were recorded. Standard p.a. CXR and HRCT of the lung and spirometry were performed. The findings of CXR, HRCT and clinical and spirometry results were scored between 0 and 3 according to the severity of the findings. Results: HRCT abnormality was detected in all 50 patients (100%), while CXR was abnormal in 40 patients (80%). The most common HRCT findings was airway abnormalities (bronchial wall thickening in 100% of cases). Other important findings were suggestive of interstitial lung disease (ILD) (80%), bronchiectasis (26%), and emphysema (24%). A statistically significant correlation was found between the severity of clinical presentation and that of the HCTR scores in patients with bronchiectasis, bronchitis and ILD (p< 0.05), but not with severity scores of HRCT in patients with emphysema. No significant correlation was found between severity scores of CXR findings. HRCT evidence of bronchial wall thickening and with a lower frequency ILD were present despite normal CXR in 20% of the patients. Conclusion: The results of this study suggest that bronchial wall thickening, ILD and emphysema are common chronic pulmonary sequelae of sulfur mustard injury. HRCT of the chest should be considered as the imaging modality of choice in chemical war injury.

  17. HIGH-Resolution CT in Chronic Pulmonary Changes after Mustard Gas Exposure

    International Nuclear Information System (INIS)

    Purpose: To identify the findings of high-resolution CT (HRCT) of the lung in patients with previous sulfur mustard gas exposure, and to correlate these findings with clinical and chest X-ray (CXR) results. Material and Methods: 50 consecutive patients were studied prospectively. The clinical data were recorded. Standard p.a. CXR and HRCT of the lung and spirometry were performed. The findings of CXR, HRCT and clinical and spirometry results were scored between 0 and 3 according to the severity of the findings. Results: HRCT abnormality was detected in all 50 patients (100%), while CXR was abnormal in 40 patients (80%). The most common HRCT findings was airway abnormalities (bronchial wall thickening in 100% of cases). Other important findings were suggestive of interstitial lung disease (ILD) (80%), bronchiectasis (26%), and emphysema (24%). A statistically significant correlation was found between the severity of clinical presentation and that of the HCTR scores in patients with bronchiectasis, bronchitis and ILD (p< 0.05), but not with severity scores of HRCT in patients with emphysema. No significant correlation was found between severity scores of CXR findings. HRCT evidence of bronchial wall thickening and with a lower frequency ILD were present despite normal CXR in 20% of the patients. Conclusion: The results of this study suggest that bronchial wall thickening, ILD and emphysema are common chronic pulmonary sequelae of sulfur mustard injury. HRCT of the chest should be considered as the imaging modality of choice in chemical war injury

  18. BK channel β1 and β4 auxiliary subunits exert opposite influences on escalated ethanol drinking in dependent mice.

    Science.gov (United States)

    Kreifeldt, Max; Le, David; Treistman, Steven N; Koob, George F; Contet, Candice

    2013-01-01

    Large conductance calcium-activated potassium (BK) channels play a key role in the control of neuronal activity. Ethanol is a potent activator of BK channel gating, but how this action may impact ethanol drinking still remains poorly understood. Auxiliary β subunits are known to modulate ethanol-induced potentiation of BK currents. In the present study, we investigated whether BK β1 and β4 subunits influence voluntary ethanol consumption using knockout (KO) mice. In a first experiment, mice were first subjected to continuous two-bottle choice (2BC) and were then switched to intermittent 2BC, which progressively increased ethanol intake as previously described in wildtype mice. BK β1 or β4 subunit deficiency did not affect ethanol self-administration under either schedule of access. In a second experiment, mice were first trained to drink ethanol in a limited-access 2BC paradigm. BK β1 or β4 deletion did not affect baseline consumption. Weeks of 2BC were then alternated with weeks of chronic intermittent ethanol (CIE) or air inhalation. As expected, a gradual escalation of ethanol drinking was observed in dependent wildtype mice, while intake remained stable in non-dependent wildtype mice. However, CIE exposure only produced a mild augmentation of ethanol consumption in BK β4 KO mice. Conversely, ethanol drinking increased after fewer CIE cycles in BK β1 KO mice than in wildtype mice. In conclusion, BK β1 or β4 did not influence voluntary ethanol drinking in non-dependent mice, regardless of the pattern of access to ethanol. However, deletion of BK β4 attenuated, while deletion of BK β1 accelerated, the escalation of ethanol drinking during withdrawal from CIE. Our data suggest that BK β1 and β4 subunits have an opposite influence on the negative reinforcing properties of ethanol withdrawal. Modulating the expression, distribution or interactions of BK channel auxiliary subunits may therefore represent a novel avenue for the treatment of alcoholism

  19. BK channel β1 and β4 auxiliary subunits exert opposite influences on escalated ethanol drinking in dependent mice

    Directory of Open Access Journals (Sweden)

    Max eKreifeldt

    2013-12-01

    Full Text Available Large conductance calcium-activated potassium (BK channels play a key role in the control of neuronal activity. Ethanol is a potent activator of BK channel gating, but how this action may impact ethanol drinking still remains poorly understood. Auxiliary β subunits are known to modulate ethanol-induced potentiation of BK currents. In the present study, we investigated whether BK β1 and β4 subunits influence voluntary ethanol consumption using knockout mice. In a first experiment, mice were first subjected to continuous two-bottle choice (2BC and were then switched to intermittent 2BC, which progressively increased ethanol intake as previously described in wildtype mice. BK β1 or β4 subunit deficiency did not affect ethanol self-administration under either schedule of access. In a second experiment, mice were first trained to drink ethanol in a limited-access 2BC paradigm. BK β1 or β4 deletion did not affect baseline consumption. Weeks of 2BC were then alternated with weeks of chronic intermittent ethanol (CIE or air inhalation. As expected, a gradual escalation of ethanol drinking was observed in dependent wildtype mice, while intake remained stable in non-dependent wildtype mice. However, CIE exposure only produced a mild augmentation of ethanol consumption in BK β4 knockout mice. Conversely, ethanol drinking increased after fewer CIE cycles in BK β1 knockout mice than in wildtype mice. In conclusion, BK β1 or β4 did not influence voluntary ethanol drinking in non-dependent mice, regardless of the pattern of access to ethanol. However, deletion of BK β4 attenuated, while deletion of BK β1 accelerated, the escalation of ethanol drinking during withdrawal from CIE. Our data suggest that BK β1 and β4 subunits have an opposite influence on the negative reinforcing properties of ethanol withdrawal. Modulating the expression, distribution or interactions of BK channel auxiliary subunits may therefore represent a novel avenue for the

  20. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    Energy Technology Data Exchange (ETDEWEB)

    Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

    2006-07-01

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  1. Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

    International Nuclear Information System (INIS)

    Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

  2. Chronic hydrocarbon exposure of harlequin ducks in areas affected by the Selendang Ayu oil spill at Unalaska Island, Alaska

    Science.gov (United States)

    Flint, Paul L.; Schamber, J.L.; Trust, K.A.; Miles, A.K.; Henderson, J.D.; Wilson, B.W.

    2012-01-01

    We evaluated chronic exposure of harlequin ducks (Histrionicus histrionicus) to hydrocarbons associated with the 2004 M/V Selendang Ayu oil spill at Unalaska Island, Alaska. We measured levels of hepatic 7-ethoxyresorufin-O-deethylase activity (EROD) in liver biopsy samples as an indicator of hydrocarbon exposure in three oiled bays and one reference bay in 2005, 2006, and 2008. Median EROD activity in ducks from oiled bays was significantly higher than in the reference bay in seven of nine pairwise comparisons. These results indicated that harlequin ducks were exposed to lingering hydrocarbons more than three years after the spill.

  3. Plants experiencing chronic internal exposure to ionizing radiation exhibit higher frequency of homologous recombination than acutely irradiated plants

    Energy Technology Data Exchange (ETDEWEB)

    Kovalchuk, O.; Kovalchuk, I.; Hohn, B. [Friedrich Miescher Institute, P.O. Box 2543, CH-4002 Basel (Switzerland); Arkhipov, A. [Chernobyl Scientific and Technical Center of International Research, Shkolnaya Str. 6, 255620 Chernobyl (Ukraine); Barylyak, I.; Karachov, I. [Ukrainian Scientific Genetics Center, Popudrenko Str. 50, 253660 Kiev (Ukraine); Titov, V. [Ivano-Frankivsk State Medical Academy, Galitska Str.2, 284000 Ivano-Frankivsk (Ukraine)

    2000-04-03

    Ionizing radiation (IR) is a known mutagen responsible for causing DNA strand breaks in all living organisms. Strand breaks thus created can be repaired by different mechanisms, including homologous recombination (HR), one of the key mechanisms maintaining genome stability [A. Britt, DNA damage and repair in plants, Annu. Rev. Plant. Phys. Plant Mol. Biol., 45 (1996) 75-100; H. Puchta, B. Hohn, From centiMorgans to basepairs: homologous recombination in plants, Trends Plant Sci., 1 (1996) 340-348.]. Acute or chronic exposure to IR may have different influences on the genome integrity. Although in a radioactively contaminated environment plants are mostly exposed to chronic pollution, evaluation of both kinds of influences is important. Estimation of the frequency of HR in the exposed plants may serve as an indication of genome stability. We used previously generated Arabidopsis thaliana and Nicotiana tabacum plants, transgenic for non-active versions of the {beta}-glucoronidase gene (uidA) [P. Swoboda, S. Gal, B. Hohn, H. Puchta, Intrachromosomal homologous recombination in whole plants, EMBO J., 13 (1994) 484-489; H. Puchta, P. Swoboda, B. Hohn, Induction of homologous DNA recombination in whole plants, Plant, 7 (1995) 203-210.] serving as a recombination substrate, to study the influence of acute and chronic exposure to IR on the level of HR as example of genome stability in plants. Exposure of seeds and seedlings to 0.1 to 10.0 Gy 60Co resulted in increased HR frequency, although the effect was more pronounced in seedlings. For the study of the influence of chronic exposure to IR, plants were grown on two chemically different types of soils, each artificially contaminated with equal amounts of 137Cs. We observed a strong and significant correlation between the frequency of HR in plants, the radioactivity of the soil samples and the doses of radiation absorbed by plants (in all cases r0.9, n=6, P<0.05). In addition, we noted that plants grown in soils with

  4. Plants experiencing chronic internal exposure to ionizing radiation exhibit higher frequency of homologous recombination than acutely irradiated plants

    International Nuclear Information System (INIS)

    Ionizing radiation (IR) is a known mutagen responsible for causing DNA strand breaks in all living organisms. Strand breaks thus created can be repaired by different mechanisms, including homologous recombination (HR), one of the key mechanisms maintaining genome stability [A. Britt, DNA damage and repair in plants, Annu. Rev. Plant. Phys. Plant Mol. Biol., 45 (1996) 75-100; H. Puchta, B. Hohn, From centiMorgans to basepairs: homologous recombination in plants, Trends Plant Sci., 1 (1996) 340-348.]. Acute or chronic exposure to IR may have different influences on the genome integrity. Although in a radioactively contaminated environment plants are mostly exposed to chronic pollution, evaluation of both kinds of influences is important. Estimation of the frequency of HR in the exposed plants may serve as an indication of genome stability. We used previously generated Arabidopsis thaliana and Nicotiana tabacum plants, transgenic for non-active versions of the β-glucoronidase gene (uidA) [P. Swoboda, S. Gal, B. Hohn, H. Puchta, Intrachromosomal homologous recombination in whole plants, EMBO J., 13 (1994) 484-489; H. Puchta, P. Swoboda, B. Hohn, Induction of homologous DNA recombination in whole plants, Plant, 7 (1995) 203-210.] serving as a recombination substrate, to study the influence of acute and chronic exposure to IR on the level of HR as example of genome stability in plants. Exposure of seeds and seedlings to 0.1 to 10.0 Gy 60Co resulted in increased HR frequency, although the effect was more pronounced in seedlings. For the study of the influence of chronic exposure to IR, plants were grown on two chemically different types of soils, each artificially contaminated with equal amounts of 137Cs. We observed a strong and significant correlation between the frequency of HR in plants, the radioactivity of the soil samples and the doses of radiation absorbed by plants (in all cases r0.9, n=6, P<0.05). In addition, we noted that plants grown in soils with different

  5. PROVANN: Model System for Chronic Exposure of Larval and Adult Fish to Releases from Offshore Petroleum Platforms

    International Nuclear Information System (INIS)

    Produced water from offshore oil and gas production platforms contains a variety of hydrocarbons, heavy metals, and production chemicals. Vertical and horizontal mixing generally brings concentrations in discharge plumes below level associated with acute effects within 500 or 1000 m of the source. Chronic effects outside this region remain a potential problem. The purpose of PROVANN, the system of models described in this paper, is to assess the potential for chronic effects from produced water. The preliminary focus is on potential bioaccumulation and boimagnification of produced water constituents in the marine food web. Other possible types of chronic effects, such as reduced fecundity, or pheromone response interference, can also be assessed to the extent that such effects may be correlated with exposure. PROVANN simulates 3-dimensional transport, dilution, and degradation of chemicals released into the water, from one or more simultaneous sources. 8 refs., 10 figs., 3 tabs

  6. Chronic Exposure to Zinc Chromate Induces Centrosome Amplification and Spindle Assembly Checkpoint Bypass in Human Lung Fibroblasts

    OpenAIRE

    Holmes, Amie L.; Wise, Sandra S.; Pelsue, Stephen C.; Aboueissa, AbouEl-Makarim; Lingle, Wilma; Salisbury, Jeffery; Gallagher, Jamie; Wise, John Pierce

    2010-01-01

    Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens. Solubility plays an important role in its carcinogenicity with the particulate or insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc chromate appears to be the most potent carcinogen, however, very few studies have investigated its carcinogenic mechanism. In this study, we investigated the ability of chronic exposure to zinc chromate to induce numerical chromosome instability. We found no inc...

  7. Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice.

    OpenAIRE

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima; Trak-Smayra, Viviane; Martinais, Sophie; Porceddu, Mathieu; Robin, Marie-Anne; Fromenty, Bernard

    2014-01-01

    International audience Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations r...

  8. Use of Polar Organic Chemical Integrative Samplers to assess the effects of chronic pesticide exposure on biofilms

    OpenAIRE

    Morin, S.; Pesce, S.; Kim Tiam, S.; Libert, X.; Coquery, M.; Mazzella, N.

    2012-01-01

    The responses of aquatic organisms to chronic exposure to environmental concentrations of toxicants, often found in mixtures, are poorly documented. Here passive sampler extracts were used in experimental contamination of laboratory channels, to investigate their effects on natural biofilm communities. A realistic mixture of pesticides extracted from POCIS (Polar Organic Chemical Integrative Samplers) was used to expose biofilms in laboratory channels to total pesticide concentrations averagi...

  9. CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronic arsenic exposure

    OpenAIRE

    Huang, S.; Guo, S.; Guo, F; Yang, Q.; XIAO, X.; Murata, M.; Ohnishi, S.; Kawanishi, S; Ma, N

    2013-01-01

    Inorganic arsenic is a well-known human skin carcinogen. Chronic arsenic exposure results in various types of human skin lesions, including squamous cell carcinoma (SCC). To investigate whether mutant stem cells participate in arsenic-associated carcinogenesis, we repeatedly exposed the human spontaneously immortalized skin keratinocytes (HaCaT) cell line to an environmentally relevant level of arsenic (0.05 ppm) in vitrofor 18 weeks. Following sodium arsenite administration, cell cycle, colo...

  10. Neutralisation of interleukin-13 in mice prevents airway pathology caused by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Kate L Tomlinson

    Full Text Available BACKGROUND: Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13 in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM. METHODOLOGY/PRINCIPAL FINDINGS: Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb administered subcutaneously (s.c.. Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR by invasive measurement of lung resistance (R(L and dynamic compliance (C(dyn. Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05 the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05 the increase in baseline R(L and the decrease in baseline C(dyn caused by chronic exposure to inhaled HDM. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.

  11. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  12. Effects of Chronic and Acute Ozone Exposure on Lipid Peroxidation and Antioxidant Capacity in Healthy Young Adults

    OpenAIRE

    Chen, Connie; Arjomandi, Mehrdad; Balmes, John; Tager, Ira; Holland, Nina

    2007-01-01

    Background There is growing evidence for the role of oxidative damage in chronic diseases. Although ozone (O3) is an oxidant pollutant to which many people are exposed, few studies have examined whether O3 induces oxidative stress in humans. Objectives This study was designed to assess the effect of short-and long-term O3 exposures on biomarkers of oxidative stress in healthy individuals. Methods Biomarkers of lipid peroxidation, 8-isoprostane (8-iso-PGF), and antioxidant capacity ferric redu...

  13. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    International Nuclear Information System (INIS)

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  14. Chronic CO2 exposure markedly increases the incidence of cataracts in juvenile Atlantic cod Gadus morhua L

    DEFF Research Database (Denmark)

    Moran, Damian; Tubbs, Lincoln; Støttrup, Josianne G.

    2012-01-01

    A study was undertaken to test the affect of chronic exposure to elevated dissolved carbon dioxide on juvenile Atlantic cod. The CO2 treatment concentrations were designated as low (1–2mgL−1, 1000μatm), medium (8mgL−1, 3500μatm) and high (18mgL−1, 8500μatm), and the fish were reared at 10°C and 2...

  15. Association between Blood Dioxin Level and Chronic Kidney Disease in an Endemic Area of Exposure.

    Directory of Open Access Journals (Sweden)

    Chien-Yuan Huang

    Full Text Available Dioxin is an industrial pollutant related to various diseases, but epidemiological data on its effects on the kidney are limited. Therefore, we conducted a study to evaluate the association between dioxin exposure and chronic kidney disease (CKD and identify the related factors.We conducted a community-based cross-sectional study and recruited participants from an area where the residents were exposed to dioxin released from a factory. We defined a "high dioxin level" as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs ≥ 20 pg WHO98-TEQDF/g lipid in the serum and defined CKD as having an estimated glomerular filtration rate (e-GFR ≤ 60 mL/min/1.73m2 or a diagnosis of CKD by a physician. The renal function was assessed between 2005 and 2010, and we excluded those who had had kidney diseases before the study started. Comparisons between patients of CKD and those who did not have CKD were made to identify the risk factors for CKD.Of the 2898 participants, 1427 had high dioxin levels, and 156 had CKD. In the univariate analyses, CKD was associated with high dioxin levels, age, gender, metabolic syndrome, diabetes mellitus, hypertension, and high insulin and uric acid levels. After adjusting for other factors, we found high dioxin levels (adjusted odds ratio [AOR] = 1.76, 95% confidence interval [CI]: 1.04-2.99, female gender (AOR = 1.74, 95%CI: 1.20-2.53, hypertension (AOR = 1.68, 95%CI: 1.17-2.42, high insulin levels (AOR = 2.14, 95% CI: 1.26-3.61, high uric acid levels (AOR = 4.25, 95% CI: 2.92-6.20, and older age (AOR = 4.66, 95% CI: 1.87-11.62 for 40-64 year and AOR = 26.66, 95% CI: 10.51-67.62 for age ≥ 65 year were independent predictors of CKD.A high dioxin level was associated with an increased prevalence of CKD. Therefore, the kidney function of populations with exposure to dioxin should be monitored.

  16. Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

    Science.gov (United States)

    Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

    2015-11-01

    Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history. PMID:26241170

  17. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  18. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  19. Considerations when using longitudinal cohort studies to assess dietary exposure to inorganic arsenic and chronic health outcomes.

    Science.gov (United States)

    Scrafford, Carolyn G; Barraj, Leila M; Tsuji, Joyce S

    2016-07-01

    Dietary arsenic exposure and chronic health outcomes are of interest, due in part to increased awareness and data available on inorganic arsenic levels in some foods. Recent concerns regarding levels of inorganic arsenic, the primary form of arsenic of human health concern, in foods are based on extrapolation from adverse health effects observed at high levels of inorganic arsenic exposure; the potential for the occurrence of these health effects from lower levels of dietary inorganic arsenic exposure has not been established. In this review, longitudinal cohort studies are evaluated for their utility in estimating dietary inorganic arsenic exposure and quantifying statistically reliable associations with health outcomes. The primary limiting factor in longitudinal studies is incomplete data on inorganic arsenic levels in foods combined with the aggregation of consumption of foods with varying arsenic levels into a single category, resulting in exposure misclassification. Longitudinal cohort studies could provide some evidence to evaluate associations of dietary patterns related to inorganic arsenic exposure with risk of arsenic-related diseases. However, currently available data from longitudinal cohort studies limit causal analyses regarding the association between inorganic arsenic exposure and health outcomes. Any conclusions should therefore be viewed with knowledge of the analytical and methodological limitations. PMID:27155067

  20. The potential immune modulatory effect of chronic bisphenol A exposure on gene regulation in male medaka (Oryzias latipes) liver.

    Science.gov (United States)

    Qiu, Wenhui; Shen, Yang; Pan, Chenyuan; Liu, Shuai; Wu, Minghong; Yang, Ming; Wang, Ke-Jian

    2016-08-01

    Bisphenol A (BPA) is a well-known estrogenic endocrine disrupting chemical (EDC) ubiquitously present in various environmental media. The present study aims to identify the responsive genes in male fish chronically exposed to low concentrations of BPA at the transcription level. We screened genes from a suppression subtractive hybridization library constructed from male medaka (Oryzias latipes) livers after 60-d exposure to 10μg/L BPA under the condition at which changes of hepatic antioxidant parameters have been previously reported. The identified genes were predicted to be involved in multiple biological processes including antioxidant physiology, endocrine system, detoxification, notably associated with the immune response processes. With real time PCR analysis, the immune-associated genes including hepcidin-like precursor, complement component and factors, MHC class I, alpha-2-macroglobulin and novel immune-type receptor 6 isoform were significantly up-regulated in a nonmonotonic dose response pattern in livers upon exposure to different concentrations of BPA (0.1, 1, 10, 100, 1000μg/L). Our results demonstrated a negative impact on gene regulation in fish chronically exposed to relatively low and environmentally relevant concentrations of BPA, and suggested the potential immune modulatory effect of chronic EDC exposure on fish. The immunotoxicity of BPA and other EDCs should be much concerned for the health of human beings and other vertebrates exposed to it. PMID:27104808

  1. Uncertainty and sensitivity analysis of chronic exposure results with the MACCS reactor accident consequence model

    International Nuclear Information System (INIS)

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the chronic exposure pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 75 imprecisely known input variables on the following reactor accident consequences are studied: crop growing season dose, crop long-term dose, water ingestion dose, milk growing season dose, long-term groundshine dose, long-term inhalation dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, total latent cancer fatalities, area-dependent cost, crop disposal cost, milk disposal cost, population-dependent cost, total economic cost, condemnation area, condemnation population, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: dry deposition velocity, transfer of cesium from animal feed to milk, transfer of cesium from animal feed to meat, ground concentration of Cs-134 at which the disposal of milk products will be initiated, transfer of Sr-90 from soil to legumes, maximum allowable ground concentration of Sr-90 for production of crops, fraction of cesium entering surface water that is consumed in drinking water, groundshine shielding factor, scale factor defining resuspension, dose reduction associated with decontamination, and ground concentration of 1-131 at which disposal of crops will be initiated due to accidents that occur during the growing season

  2. Effect of chronic pesticide exposure in farm workers of a Mexico community.

    Science.gov (United States)

    Payán-Rentería, Rolando; Garibay-Chávez, Guadalupe; Rangel-Ascencio, Raul; Preciado-Martínez, Veronica; Muñoz-Islas, Laura; Beltrán-Miranda, Claudia; Mena-Munguía, Salvador; Jave-Suárez, Luis; Feria-Velasco, Alfredo; De Celis, Ruth

    2012-01-01

    Pesticides are frequently used substances worldwide, even when the use of some of them is forbidden due to the recognized adverse effect they have on the health of not only the people who apply the pesticides, but also of those that consume the contaminated products. The objectives of this study were to know the health issues of farm workers chronically exposed to pesticides, to evaluate possible damage at genetic level, as well as to explore some hepatic, renal, and hematological alterations. A transversal comparative study was performed between 2 groups, one composed of 25 farm workers engaged in pesticide spraying, and a control group of 21 workers not exposed to pesticides; both groups belonged to the Nextipac community in Jalisco, Mexico. Each member of both groups underwent a full medical history. Blood samples were taken from all farm workers in order to obtain a complete blood count and chemistry, clinical chemistry, lipid profile, liver and kidney function tests, erythrocyte cholinesterase quantification, lipid peroxidation profile, and free DNA fragment quantification. For the information analysis, central tendency and dispersion measurements were registered. In order to know the differences between groups, a cluster multivariate method was used, as well as prevalence reasons. The most used pesticides were mainly organophosphates, triazines and organochlorine compounds. The exposed group showed acute poisoning (20% of the cases) and diverse alterations of the digestive, neurological, respiratory, circulatory, dermatological, renal, and reproductive system probably associated to pesticide exposure. More importantly, they presented free DNA fragments in plasma (90.8 vs 49.05 ng/mL) as well as a higher level of lipid peroxidation (41.85 vs. 31.91 nmol/mL) in comparison with those data from unexposed farm workers. These results suggest that there exist health hazards for those farm workers exposed to pesticides, at organic and cellular levels. PMID:22315932

  3. Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

    International Nuclear Information System (INIS)

    Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg-1·d-1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F0 rats were detected, as well as the survival rate and weight of F1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na+-K+-ATPase decreased in F1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F1 generation was observed at any dose. (authors)

  4. Uncertainty and sensitivity analysis of chronic exposure results with the MACCS reactor accident consequence model

    International Nuclear Information System (INIS)

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the chronic exposure pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 75 imprecisely known input variables on the following reactor accident consequences are studied: crop growing-season dose, crop long-term dose, water ingestion dose, milk growing-season dose, long-term groundshine dose, long-term inhalation dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, total latent cancer fatalities, area-dependent cost, crop disposal cost, milk disposal cost, population-dependent cost, total economic cost, condemnation area, condemnation population, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: dry deposition velocity, transfer of cesium from animal feed to milk, transfer of cesium from animal feed to meet, ground concentration of Cs-134 at which the disposal of milk products will be initiated, transfer of Sr-90 from soil to legumes, maximum allowable ground concentration of Sr-90 for production of crops, fraction of cesium entering surface water that is consumed in drinking water, groundshine shielding factor, scale factor defining resuspension, dose reduction associated with decontamination, and ground concentration of I-131 at which disposal of crops will be initiated due to accidents that occur during the growing season. Reducing the uncertainty in the preceding variables was found to substantially reduce the uncertainty in the

  5. Micronucleus assay in human lymphocytes as a bio dosimeter of in vivo acute and chronic exposures

    International Nuclear Information System (INIS)

    To assess the persistence over time of micronuclei (MN) in lymphocytes of cancer patients after radiotherapy and, consequently, to verify the suitability of MN test as a dosimeter for monitoring in vivo ionizing radiation damage, the cytokinesis-blocked MN assay was applied in peripheral blood lymphocytes of cervix and head and neck cancer patients (n = 34). The evaluation of data suggests that: 1) MN frequency increases linearly with the equivalent total-body absorbed dose (R2 = 0,9; P=0,015); 2) The distribution of the MN yields deviates significantly from Poisson with the increase of equivalent total-body dose (σ2/y = 1,14 mean value); 3) The comparison of spontaneous MN frequencies in healthy subjects with those in cancer patients, prior to radiotherapy, shows significant differences (p<0,01); and 4) It is observed a general decline in MN frequencies with time after radiotherapy, with considerable variations between patients. The kinetics of elimination of MN seems to follow a two-term exponential function, with a short and a long term. Patients with the highest equivalent total-body dose (total tumoral dose: 60-80 Gy) initially tend to have the fastest decline. At 6-18 months of follow-up time 11 of the 17 patients, evaluated 2-480 months post-treatment, showed higher frequencies of MN than their respective levels before radiation therapy, indicating persistence of radiation induced cytogenetic damage. Further studies modeling changes in chromosome aberrations with acute and chronic exposures should provide perspectives on biological dosimetry in accident situations in which there is a blood sampling delay and on biological monitoring of human populations exposed to ionizing radiation. (author)

  6. Uncertainty and sensitivity analysis of chronic exposure results with the MACCS reactor accident consequence model

    Energy Technology Data Exchange (ETDEWEB)

    Helton, J.C. [Arizona State Univ., Tempe, AZ (United States); Johnson, J.D.; Rollstin, J.A. [Gram, Inc., Albuquerque, NM (United States); Shiver, A.W.; Sprung, J.L. [Sandia National Labs., Albuquerque, NM (United States)

    1995-01-01

    Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the chronic exposure pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 75 imprecisely known input variables on the following reactor accident consequences are studied: crop growing season dose, crop long-term dose, water ingestion dose, milk growing season dose, long-term groundshine dose, long-term inhalation dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, total latent cancer fatalities, area-dependent cost, crop disposal cost, milk disposal cost, population-dependent cost, total economic cost, condemnation area, condemnation population, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: dry deposition velocity, transfer of cesium from animal feed to milk, transfer of cesium from animal feed to meat, ground concentration of Cs-134 at which the disposal of milk products will be initiated, transfer of Sr-90 from soil to legumes, maximum allowable ground concentration of Sr-90 for production of crops, fraction of cesium entering surface water that is consumed in drinking water, groundshine shielding factor, scale factor defining resuspension, dose reduction associated with decontamination, and ground concentration of 1-131 at which disposal of crops will be initiated due to accidents that occur during the growing season.

  7. The acute and sub-chronic exposures of goldfish to naphthenic acids induce different host defense responses.

    Science.gov (United States)

    Hagen, Mariel O; Garcia-Garcia, Erick; Oladiran, Ayoola; Karpman, Matthew; Mitchell, Scott; El-Din, Mohamed Gamal; Martin, Jonathan W; Belosevic, Miodrag

    2012-03-01

    Naphthenic acids (NAs) are believed to be the major toxic component in oil sands process-affected water (OSPW) produced by the oil sands mining industry in Northern Alberta, Canada. We recently reported that oral exposure to NAs alters mammalian immune responses, but the effect of OSPW or NAs on the immune mechanisms of aquatic organisms has not been fully elucidated. We analyzed the effects of acute and sub-chronic NAs exposures on goldfish immune responses by measuring the expression of three pro-inflammatory cytokine genes, antimicrobial functions of macrophages, and host defense after challenge with a protozoan pathogen (Trypanosoma carassii). One week after NAs exposure, fish exhibited increased expression of pro-inflammatory cytokines (IFNγ, IL-1β1, TNF-α2) in the gills, kidney and spleen. Primary macrophages from fish exposed to NAs for one week, exhibited increased production of nitric oxide and reactive oxygen intermediates. Goldfish exposed for one week to 20 mg/L NAs were more resistant to infection by T. carassii. In contrast, sub-chronic exposure of goldfish (12 weeks) to NAs resulted in decreased expression of pro-inflammatory cytokines in the gills, kidney and spleen. The sub-chronic exposure to NAs reduced the ability of goldfish to control the T. carassii infection, exemplified by a drastic increase in fish mortality and increased blood parasite loads. This is the first report analyzing the effects of OSPW contaminants on the immune system of aquatic vertebrates. We believe that the bioassays depicted in this work will be valuable tools for analyzing the efficacy of OSPW remediation techniques and assessment of diverse environmental pollutants. PMID:22227375

  8. Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice

    Science.gov (United States)

    Hu, Wei

    Background: The medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol exposure is unknown. Here we explored the effects of acamprosate on an attentional set-shifting task, and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons. Methods: We induced alcohol dependence in mice via chronic intermittent ethanol (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2-bottle choice paradigm. Impairments of executive function were assessed in an attentional set-shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol-induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices. Results: Chronic ethanol exposure impaired cognitive flexibility in the attentional set-shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic ethanol exposure increased use-dependent presynaptic transmitter release and enhanced postsynaptic N-methyl-D-aspartate receptor (NMDAR) function. Moreover, CIE-treatment lowered input resistance, and decreased the threshold and the afterhyperpolarization (AHP) of action potentials, suggesting chronic ethanol exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these ethanol-induced changes cellular function. Conclusion: Acamprosate improved attentional control of ethanol exposed animals

  9. Elevated glutathione level does not protect against chronic alcohol mediated apoptosis in recombinant human hepatoma cell line VL-17A over-expressing alcohol metabolizing enzymes--alcohol dehydrogenase and Cytochrome P450 2E1.

    Science.gov (United States)

    Chandrasekaran, Karthikeyan; Swaminathan, Kavitha; Kumar, S Mathan; Chatterjee, Suvro; Clemens, Dahn L; Dey, Aparajita

    2011-06-01

    Chronic consumption of alcohol leads to liver injury. Ethanol-inducible Cytochrome P450 2E1 (CYP2E1) plays a critical role in alcohol mediated oxidative stress due to its ability to metabolize ethanol. In the present study, using the recombinant human hepatoma cell line VL-17A that over-expresses the alcohol metabolizing enzymes-alcohol dehydrogenase (ADH) and CYP2E1; and control HepG2 cells, the mechanism and mode of cell death due to chronic ethanol exposure were studied. Untreated VL-17A cells exhibited apoptosis and oxidative stress when compared with untreated HepG2 cells. Chronic alcohol exposure, i.e., 100 mM ethanol treatment for 72 h caused a significant decrease in viability (47%) in VL-17A cells but not in HepG2 cells. Chronic ethanol mediated cell death in VL-17A cells was predominantly apoptotic, with increased oxidative stress as the underlying mechanism. Chronic ethanol exposure of VL-17A cells resulted in 1.1- to 2.5-fold increased levels of ADH and CYP2E1. Interestingly, the level of the antioxidant GSH was found to be 3-fold upregulated in VL-17A cells treated with ethanol, which may be a metabolic adaptation to the persistent and overwhelming oxidative stress. In conclusion, the increased GSH level may not be sufficient enough to protect VL-17A cells from chronic alcohol mediated oxidative stress and resultant apoptosis. PMID:21414402

  10. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    International Nuclear Information System (INIS)

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  11. Gene expression and pathologic alterations in juvenile rainbow trout due to chronic dietary TCDD exposure

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qing [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States); Rise, Matthew L. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Spitsbergen, Jan M. [Department of Microbiology, Oregon State University, 220 Nash Hall, Corvallis, OR 97331 (United States); Hori, Tiago S. [Ocean Sciences Centre, Memorial University of Newfoundland, 1 Marine Lab Road, St. John' s, NL, A1C 5S7 (Canada); Mieritz, Mark; Geis, Steven [Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706 (United States); McGraw, Joseph E. [School of Pharmacy, Concordia University Wisconsin, 12800 North Lake Shore Drive, Mequon, WI 53097 (United States); Goetz, Giles [School of Aquatic and Fishery Sciences, University of Washington, 1122 Northeast Boat Street, Seattle, WA 98195 (United States); Larson, Jeremy; Hutz, Reinhold J. [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); Carvan, Michael J., E-mail: carvanmj@uwm.edu [Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, 3209 N. Maryland Ave., Milwaukee, WI 53211 (United States); School of Freshwater Sciences, University of Wisconsin-Milwaukee, 600 E Greenfield Ave, Milwaukee, WI 53204 (United States)

    2013-09-15

    Highlights: •First report of the effects of dietary TCDD in juvenile trout smaller than 20 g. •TCDD uptake was estimated using published models and confirmed by GC. •First report of dietary TCDD-induced lesions in nasal epithelium in any species. •Several useful biomarkers are identified from microarray-based transcriptomics analysis. -- Abstract: The goal of this project was to use functional genomic methods to identify molecular biomarkers as indicators of the impact of TCDD exposure in rainbow trout. Specifically, we investigated the effects of chronic dietary TCDD exposure on whole juvenile rainbow trout global gene expression associated with histopathological analysis. Juvenile rainbow trout were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb (ng TCDD/g food), and fish were sampled from each group at 7, 14, 28 and 42 days after initiation of feeding. 100 ppb TCDD caused 100% mortality at 39 days. Fish fed with 100 ppb TCDD food had TCDD accumulation of 47.37 ppb (ng TCDD/g fish) in whole fish at 28 days. Histological analysis from TCDD-treated trout sampled from 28 and 42 days revealed that obvious lesions were found in skin, oropharynx, liver, gas bladder, intestine, pancreas, nose and kidney. In addition, TCDD caused anemia in peripheral blood, decreases in abdominal fat, increases of remodeling of fin rays, edema in pericardium and retrobulbar hemorrhage in the 100 ppb TCDD-treated rainbow trout compared to the control group at 28 days. Dose- and time-dependent global gene expression analyses were performed using the cGRASP 16,000 (16K) cDNA microarray. TCDD-responsive whole body transcripts identified in the microarray experiments have putative functions involved in various biological processes including growth, cell proliferation, metabolic process, and immune system processes. Nine microarray-identified genes were selected for QPCR validation. CYP1A3 and CYP1A1 were common up-regulated genes and HBB1 was a common down

  12. Ethanol poisoning

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002644.htm Ethanol poisoning To use the sharing features on this page, please enable JavaScript. Ethanol poisoning is caused by drinking too much alcohol. ...

  13. Chronic Exposure to Deoxynivalenol Has No Influence on the Oral Bioavailability of Fumonisin B1 in Broiler Chickens

    Science.gov (United States)

    Antonissen, Gunther; Devreese, Mathias; Van Immerseel, Filip; De Baere, Siegrid; Hessenberger, Sabine; Martel, An; Croubels, Siska

    2015-01-01

    Both deoxynivalenol (DON) and fumonisin B1 (FB1) are common contaminants of feed. Fumonisins (FBs) in general have a very limited oral bioavailability in healthy animals. Previous studies have demonstrated that chronic exposure to DON impairs the intestinal barrier function and integrity, by affecting the intestinal surface area and function of the tight junctions. This might influence the oral bioavailability of FB1, and possibly lead to altered toxicity of this mycotoxin. A toxicokinetic study was performed with two groups of 6 broiler chickens, which were all administered an oral bolus of 2.5 mg FBs/kg BW after three-week exposure to either uncontaminated feed (group 1) or feed contaminated with 3.12 mg DON/kg feed (group 2). No significant differences in toxicokinetic parameters of FB1 could be demonstrated between the groups. Also, no increased or decreased body exposure to FB1 was observed, since the relative oral bioavailability of FB1 after chronic DON exposure was 92.2%. PMID:25690690

  14. Uranium microdistribution in renal cortex of rats after chronic exposure: a study by secondary ion mass spectrometry microscopy.

    Science.gov (United States)

    Tessier, Christine; Suhard, David; Rebière, François; Souidi, Maâmar; Dublineau, Isabelle; Agarande, Michelle

    2012-02-01

    For a few years, the biological effects on ecosystems and the public of the bioaccumulation of radionuclides in situations of chronic exposures have been studied. This work, in keeping with the ENVIRHOM French research program, presents the uranium microdistribution by secondary ion mass spectrometry (SIMS) technique in the renal cortex of rats following chronic exposure to this low level element in the drinking water (40 mg/L) as a function to exposure duration (6, 9, 12, and 18 months). The SIMS mass spectra and 238U+ ion images produced with a SIMS CAMECA 4F-E7 show the kinetic of uranium accumulation in the different structures of the kidney. For the rats contaminated up to 12 months, the radioelement is mainly fixed in the proximal tubules; then after 18 exposure months, uranium is detected in all the segments of the nephron. This work has also shown that ion microscopy is an analytical method to detect trace elements and give elemental cartography at the micrometer scale. PMID:22217926

  15. Developmental effects induced by chronic and prolonged exposure of chicken embryos to 900 MHz GSM base station radiation

    International Nuclear Information System (INIS)

    Interference from base station radiation with embryonic development was investigated by chronic and prolonged exposure of developing chicken embryos. The latter were exposed under a 900 MHz GSM base station radiating microwaves at recommended safety level, i.e., 41 V/m. Total death rate was 7.7 times higher among radiation exposed embryos (78.5%) than among sham exposures (10.2%). Radiation exposure was associated with delayed hatching (3.2 days) and slightly but significantly increased (P<0.01) weight of hatchings. These finding indicated that base station radiation can induce lethal effect, as well as developmental retardation. They arouse questioning as to the adequacy of current safety guidelines. (author)

  16. Neural Adaptation Leads to Cognitive Ethanol Dependence

    OpenAIRE

    Robinson, Brooks G; Khurana, Sukant; Kuperman, Anna; Nigel S Atkinson

    2012-01-01

    Physiological alcohol dependence is a key adaptation to chronic ethanol consumption that underlies withdrawal symptoms, is thought to directly contribute to alcohol addiction behaviors, and is associated with cognitive problems such as deficits in learning and memory [1–3]. Based on the idea that an ethanol-adapted (dependent) animal will perform better in a learning assay than an animal experiencing ethanol withdrawal will, we have used a learning paradigm to detect physiological ethanol dep...

  17. Ethanol prevents development of destructive arthritis

    OpenAIRE

    Jonsson, Ing-Marie; Verdrengh, Margareta; Brisslert, Mikael; Lindblad, Sofia; Bokarewa, Maria; Islander, Ulrika; Carlsten, Hans; Ohlsson, Claes; Nandakumar, Kutty Selva; Holmdahl, Rikard; Tarkowski, Andrej

    2006-01-01

    Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription...

  18. Zebrafish gene expression, histology, blood domoic acid level, and behavioral data (Effects of Chronic Domoic Acid Exposure on Gene Expression in the Vertebrate CNS.)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The potential impacts of chronic algal toxin exposure have long been a concern. One HAB toxin, domoic acid (DA), is a potent neurotoxin that interacts with the...

  19. Expression of Glutamatergic Genes in Healthy Humans across 16 Brain Regions; Altered Expression in the Hippocampus after Chronic Exposure to Alcohol or Cocaine

    OpenAIRE

    Enoch, Mary-Anne; Rosser, Alexandra A.; Zhou, Zhifeng; Mash, Deborah C; Yuan, Qiaoping; Goldman, David

    2014-01-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus.

  20. Ethanol Basics

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-01-30

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  1. Effects of sub-chronic exposure to SO{sub 2} on lipid and carbohydrate metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lovati, M.R. [Institute of Pharmacological Sciences, Milan (Italy); Manzoni, C. [Institute of Pharmacological Sciences, Milan (Italy); Daldossi, M. [Institute of Pharmacological Sciences, Milan (Italy); Spolti, S. [Institute of Pharmacological Sciences, Milan (Italy); Sirtori, C.R. [Institute of Pharmacological Sciences, Milan (Italy)

    1996-01-01

    Sulfur dioxide (SO{sub 2}) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. While toxicological reports on SO{sub 2} have extensively dealt with the pulmonary system, essentially no data are available on the effects of chronic exposure to this pollutant on intermediary metabolism, although some biochemical changes in lipid metabolism have been detected. The present investigation was aimed at evaluating the effects of sub-chronic exposure to SO{sub 2} on concentrations of serum lipids/lipoproteins and on glucose metabolism, in animal models of hypercholesterolemia and diabetes. A specially designed controlinert atmosphere chamber was used, where male Sprague-Dawley rats fed on either standard or cholesterol enriched (HC) diets, as well as streptozotocin diabetics, were exposed to SO{sub 2} at 5 and 10 ppm, 24 h per day for 14 days. In rats, both on a standard diet and on a HC regimen, SO{sub 2} exposure determined a significant dose-dependent increase in plasma triglycerides, up to +363% in the 10 ppm HC exposed animals. This same gas concentration significantly reduced HDL cholesterol levels. In contrast, exposure of diabetic animals to 10 ppm SO{sub 2} resulted in a fall (-41%) of plasma and liver triglycerides and in a concomitant increase (+62%) of plasma HDL cholesterol. This discrepancy could apparently be related to diverging effects of SO{sub 2} exposure on plasma insulin levels in the different animal groups. Kinetic analyses of triglyceride synthesis carried out in rats on a standard diet revealed, in exposed animals, a significant reduction in the secretory rate, in spite of the concomitant hypertriglyceridemia. These findings suggest that SO{sub 2} exposure can markedly modify major lipid and glycemic indices, also indicating a differential response in normo/hyperlipidemic versus diabetic animals. (orig.)

  2. Efeitos da exposição pré-natal e pós-natal ao etanol no córtex cerebral de ratos: um estudo do neurópilo Effects of prenatal and postnatal ethanol exposure in the cerebral cortex of rats: a study of neuropil

    Directory of Open Access Journals (Sweden)

    Márcio Sousa Jerônimo

    2008-02-01

    Full Text Available INTRODUÇÃO: Exposição pré-natal ao etanol é freqüentemente associada a microcefalia e atraso na migração celular. O mecanismo pelo qual o etanol induz seus efeitos no desenvolvimento do sistema nervoso não é muito bem entendido. OBJETIVOS: Avaliar o efeito da exposição crônica ao etanol sobre o córtex visual de ratos durante seu desenvolvimento. MATERIAL E MÉTODO: Ratos Wistar provenientes do acasalamento de 30 fêmeas, divididos nos grupos etanol (n = 10 - 3 g/kg/dia - e controle (n = 10, foram utilizados nesse experimento. Os ratos foram perfundidos e o encéfalo, dividido em três partes: anterior, médio e posterior. Os cortes obtidos do fragmento posterior foram expostos à rotina histológica e submetidos a diferentes técnicas de coloração. Na análise estatística foi utilizado o teste t para comparar os pesos encefálicos e corporais. Considerou-se como nível de rejeição de hipótese nula um valor de p BACKGROUND: Prenatal exposure to ethanol is frequently associated with microencephaly and delayed cell migration. The mechanism by which ethanol affects the development of the nervous system is still not fully understood. OBJECTIVE: To evaluate the effect of chronic exposure to ethanol on the visual cortex of rats during their development. MATERIAL AND METHOD: Wistar rats, born from the mating of 30 females, were divided into two groups: those exposed to ethanol (n = 10 - 3 g/kg/day - and a control group (n = 10. The rats were perfused and brain was divided into three parts: anterior, middle and posterior. Slices taken from the posterior fragment were subjected to histological analysis routine and different staining techniques. A statistical analysis was carried out using t test to compare brain and body weight. A value < 0,05 was considered a rejection of null hypothesis. RESULTS: There was a reduction of brain weight in different analyzed periods. There were no fiber deposits. Ectopia and neuronal heterotopia were

  3. Effects of chronic uranium internal exposure on mortality: Results of a pilot study among French nuclear workers

    International Nuclear Information System (INIS)

    Background: This article presents the mortality data compiled among a cohort of workers at risk of internal uranium exposure and discusses the extent to which this exposure might differentiate them from other nuclear workers. Methods: The cohort consisted of 2897 Areva-NC-Pierrelatte plant workers, followed from 1 January 1968 through 31 December 2006 (79,892 person-years). Mortality was compared with that of the French population, by calculating Standardized Mortality Ratios (SMR) and 95 % confidence intervals (CI95 %). External radiation exposure was reconstructed using external dosimetry archives. Internal uranium exposure was assessed using a plant-specific job-exposure-matrix, considering six types of uranium compounds according to their nature (natural and reprocessed uranium [RPU] and solubility [fast-F, moderate-M, and slow-S]). Exposure-effect analyses were performed for causes of death known to be related to external radiation exposure (all cancers and circulatory system diseases) and cancer of uranium target-organs (lung and hematopoietic and lymphatic tissues, HLT). Results: A significant deficit of mortality from all causes (SMR = 0.58; CI95% [0.53-0.63]), all cancers (SMR = 0.72; CI95% [0.63-0.82]) and smoking related cancers was observed. Non-significant 30 %-higher increase of mortality was observed for cancer of pleura (SMR = 2.32; CI95% [0.75-5.41]), rectum and HLT, notably non-Hodgkin's lymphoma (SMR = 1.38; CI95% [0.63-2.61]) and chronic lymphoid leukemia (SMR = 2.36; CI95% [0.64-6.03]). No exposure-effect relationship was found with external radiation cumulative dose. A significant exposure-effect relationship was observed for slowly soluble uranium, particularly RPU, which was associated with an increase in mortality risk reaching 8 to 16 % per unit of cumulative exposure score and 10 to 15 % per year of exposure duration. Conclusion: The Areva-NC-Pierrelatte workers cohort presents a non-significant over-mortality from HLT cancers, notably of

  4. Metabolism of Mycotoxins, Intracellular Functions of Vitamin B12, and Neurological Manifestations in Patients with Chronic Toxigenic Mold Exposures. A Review

    OpenAIRE

    Ebere C. Anyanwu; Mohammed Morad; Campbell, Andrew W.

    2004-01-01

    This paper evaluates the possible reasons for consistent vitamin B12 deficiency in chronic toxigenic mold exposures and the synergistic relationships with the possible mycotoxic effects on one-carbon metabolism that lead to the manifestations of clinical neuropathological symptomology. Vitamins are first defined in general and the nutritional sources of vitamin B12 are evaluated in particular. Since patients with chronic exposures to toxigenic molds manifest vitamin B12 deficiencies, the role...

  5. Hair analysis following chronic smoked-drugs-of-abuse exposure in adults and their toddler: a case report

    Directory of Open Access Journals (Sweden)

    Papaseit Esther

    2011-12-01

    Full Text Available Abstract Introduction Over the past two decades, the study of chronic cocaine and crack cocaine exposure in the pediatric population has been focused on the potential adverse effects, especially in the prenatal period and early childhood. Non-invasive biological matrices have become an essential tool for the assessment of a long-term history of drug of abuse exposure. Case report We analyze the significance of different biomarker values in hair after chronic crack exposure in a two-year-old Caucasian girl and her parents, who are self-reported crack smokers. The level of benzoylecgonine, the principal metabolite of cocaine, was determined in segmented hair samples (0 cm to 3 cm from the scalp, and > 3 cm from the scalp following washing to exclude external contamination. Benzoylecgonine was detectable in high concentrations in the child's hair, at 1.9 ng/mg and 7.04 ng/mg, respectively. Benzoylecgonine was also present in the maternal and paternal hair samples at 7.88 ng/mg and 6.39 ng/mg, and 13.06 ng/mg and 12.97 ng/mg, respectively. Conclusion Based on the data from this case and from previously published poisoning cases, as well as on the experience of our research group, we conclude that, using similar matrices for the study of chronic drug exposure, children present with a higher cocaine concentration in hair and they experience more serious deleterious acute effects, probably due to a different and slower cocaine metabolism. Consequently, children must be not exposed to secondhand crack smoke under any circumstance.

  6. Accumulation and effects of Cr(VI) in Japanese medaka (Oryzias latipes) during chronic dissolved and dietary exposures.

    Science.gov (United States)

    Chen, Hongxing; Mu, Lei; Cao, Jinling; Mu, Jingli; Klerks, Paul L; Luo, Yongju; Guo, Zhongbao; Xie, Lingtian

    2016-07-01

    Chromium (Cr) is an essential metal and a nutritional supplement for both human and agricultural uses. It is also a pollutant from a variety of industrial uses. These uses can lead to elevated Cr levels in aquatic environments, where it can enter and affect aquatic organisms. Its accumulation and subsequent effects in fish have received relatively little attention, especially for chronic exposure. In the present study, Japanese medaka were chronically exposed to dissolved or dietary Cr(VI) for 3 months. Cr accumulation in liver, gills, intestine, and brain was evaluated. Effects on the antioxidant system, nervous system (acetylcholinesterase, AChE), digestive system (α-glucosidase, α-Glu), and tissue histology (liver and gills) were also assessed. Cr accumulation was observed in the intestine and liver of fish exposed to Cr-contaminated brine shrimp. However, chronic dissolved Cr exposure led to significant Cr accumulation in all organs tested. Analysis of the subcellular distribution of Cr in medaka livers revealed that 37% of the Cr was present in the heat stable protein fraction. The dissolved Cr exposure had pronounced effects on the antioxidant system in the liver, with an elevated ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) and decreases in GSH and glutathione S-transferase (GST). The α-Glu activity in the intestine was significantly inhibited. In addition, Cr exposure caused histopathological alterations in the gills and liver. In general, the effects of dietary Cr were relatively minor, possible due to the much lower accumulation in the fish. Our results imply that Japanese medaka accumulate Cr mainly via uptake of dissolved Cr(VI). PMID:27162070

  7. Chronic environmental exposure to lead affects semen quality in a Mexican men population

    Science.gov (United States)

    Morán-Martínez, Javier; Carranza-Rosales, Pilar; Morales-Vallarta, Mario; A. Heredia-Rojas, José; Bassol-Mayagoitia, Susana; Denys Betancourt-Martínez, Nadia; M. Cerda-Flores, Ricardo

    2013-01-01

    Background: Male infertility is affected by several factors. Lead is one of the heavy metals more bioavailable than usually modifies the sperm quality in humans. Objective: The aim of this study was to establish the role of lead in semen quality in environmentally exposed men. Materials and Methods: Semen and blood samples were obtained from two groups: the exposed group (EG=20) and the non-exposed group (NEG=27). Two semen aliquots were used, one to evaluate spermatic quality and the other for lead determination. Blood (PbB) and semen lead (PbS) determination was performed by atomic absorption spectrophotometry. Results: The PbB concentration was significantly greater in the EG, 10.10±0.97 µgdL-1 than in the NEG, 6.42±0.38 µgdL-1 (p<0.01), as well as the PbS concentration, with 3.28±0.35 and 1.76±0.14µgdL-1 in the EG and NEG respectively (p=0.043). A significant correlation between PbS and PbB concentration in the EG was found (r=0.573, p=0.038). Overall, the spermatic quality was lower in the EG than in the NEG. Specifically, there were significant differences in the spermatic concentration [EG=43.98±6.26 and NEG=68.78±8.51X106 cellmL-1 (p<0.01)], motility [EG=49±7 and NEG=67±4% (p=0.029)], viability [EG=36.32±3.59 and NEG=72.12±1.91% (p<0.01)] and abnormal morphology [EG=67±18 and NEG=32±12% (p<0.01)]. In the immature germ cells (IGC) concentration differences were found only for A cells (EG=8.1±1.1x100 and NEG=3.2±1.9X100 spermatozoa) (p<0.01) and for Sab cells (EG=3.4±2.2x100 and NEG=1.1±1.0X100 spermatozoa) (p=0.041). Conclusion: These results suggest that chronic environmental exposure to low levels of lead adversely affect the spermatic quality. PMID:24639755

  8. Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Klett Martin

    2005-10-01

    Full Text Available Abstract Background Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans. Methods Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37–61 years. PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180. Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 μg/l; weighted exposure duration 17.9 ± 7 years was identified and compared with 16 paired controls. Results Blood analyses indicated a moderate exposure effect size (d relative to expected background exposure for total PCB (4.45 ± 2.44 μg/l; d = 0.4. A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 ± 0.25 μg/l; d = 1.5 and 101 (0.07 ± 0.09 μg/l; d = 0.7. Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state as well as attenuated attentional performance (response shifting and alertness in a cued reaction task. Conclusion Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well

  9. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice

    International Nuclear Information System (INIS)

    Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and anti-sperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h-1) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation. (authors)

  10. Continuing Exposure to Low-Dose Nonylphenol Aggravates Adenine-Induced Chronic Renal Dysfunction and Role of Rosuvastatin Therapy

    Directory of Open Access Journals (Sweden)

    Yen Chia-Hung

    2012-07-01

    Full Text Available Abstract Background Nonylphenol (NP, an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS synthesis. Chronic exposure to low-dose adenine (AD has been reported to induce chronic kidney disease (CKD. Methods In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control, group 2 (AD in fodder at a concentration of 0.25%, group 3 (NP: 2 mg/kg/day, group 4 (combined AD & NP, and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day. Treatment was continued for 24 weeks for all animals before being sacrificed. Results By the end of 24 weeks, serum blood urea nitrogen (BUN and creatinine levels were increased in group 4 than in groups 1–3, but significantly reduced in group 5 as compared with group 4 (all p  Conclusion NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.

  11. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    International Nuclear Information System (INIS)

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As2O3

  12. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  13. Identification of 5' AMP-activated kinase as a target of reactive aldehydes during chronic ingestion of high concentrations of ethanol.

    Science.gov (United States)

    Shearn, Colin T; Backos, Donald S; Orlicky, David J; Smathers-McCullough, Rebecca L; Petersen, Dennis R

    2014-05-30

    The production of reactive aldehydes including 4-hydroxy-2-nonenal (4-HNE) is a key component of the pathogenesis in a spectrum of chronic inflammatory hepatic diseases including alcoholic liver disease (ALD). One consequence of ALD is increased oxidative stress and altered β-oxidation in hepatocytes. A major regulator of β-oxidation is 5' AMP protein kinase (AMPK). In an in vitro cellular model, we identified AMPK as a direct target of 4-HNE adduction resulting in inhibition of both H2O2 and 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR)-induced downstream signaling. By employing biotin hydrazide capture, it was confirmed that 4-HNE treatment of cells resulted in carbonylation of AMPKα/β, which was not observed in untreated cells. Using a murine model of alcoholic liver disease, treatment with high concentrations of ethanol resulted in an increase in phosphorylated as well as carbonylated AMPKα. Despite increased AMPK phosphorylation, there was no significant change in phosphorylation of acetyl CoA carboxylase. Mass spectrometry identified Michael addition adducts of 4-HNE on Cys(130), Cys(174), Cys(227), and Cys(304) on recombinant AMPKα and Cys(225) on recombinant AMPKβ. Molecular modeling analysis of identified 4-HNE adducts on AMPKα suggest that inhibition of AMPK occurs by steric hindrance of the active site pocket and by inhibition of hydrogen peroxide induced oxidation. The observed inhibition of AMPK by 4-HNE provides a novel mechanism for altered β-oxidation in ALD, and these data demonstrate for the first time that AMPK is subject to regulation by reactive aldehydes in vivo. PMID:24722988

  14. Exposure to daily ambient particulate polycyclic aromatic hydrocarbons and cough occurrence in adult chronic cough patients: A longitudinal study

    Science.gov (United States)

    Anyenda, Enoch Olando; Higashi, Tomomi; Kambayashi, Yasuhiro; Thao, Nguyen Thi Thu; Michigami, Yoshimasa; Fujimura, Masaki; Hara, Johsuke; Tsujiguchi, Hiromasa; Kitaoka, Masami; Asakura, Hiroki; Hori, Daisuke; Yamada, Yohei; Hayashi, Koichiro; Hayakawa, Kazuichi; Nakamura, Hiroyuki

    2016-09-01

    The specific components of airborne particulates responsible for adverse health effects have not been conclusively identified. We conducted a longitudinal study on 88 adult patients with chronic cough to evaluate whether exposure to daily ambient levels of particulate polycyclic aromatic hydrocarbons (PAH) has relationship with cough occurrence. Study participants were recruited at Kanazawa University Hospital, Japan and were physician-diagnosed to at least have asthma, cough variant asthma and/or atopic cough during 4th January to 30th June 2011. Daily cough symptoms were collected by use of cough diaries and simultaneously, particulate PAH content in daily total suspended particles collected on glass fiber filters were determined by high performance liquid chromatography coupled with fluorescence detector. Population averaged estimates of association between PAH exposure and cough occurrence for entire patients and subgroups according to doctor's diagnosis were performed using generalized estimating equations. Selected adjusted odds ratios for cough occurrence were 1.088 (95% confidence interval (CI): 1.031, 1.147); 1.209 (95% CI: 1.060, 1.379) per 1 ng/m3 increase for 2-day lag and 6-day moving average PAH exposure respectively. Likewise, 5 ring PAH had higher odds in comparison to 4 ring PAH. On the basis of doctor's diagnosis, non-asthma group had slightly higher odds ratio 1.127 (95% CI: 1.033, 1.228) per 1 ng/m3 increase in 2-day lag PAH exposure. Our findings suggest that ambient PAH exposure is associated with cough occurrence in adult chronic cough patients. The association may be stronger in non-asthma patients and even at low levels although there is need for further study with a larger sample size of respective diagnosis and inclusion of co-pollutants.

  15. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

    Science.gov (United States)

    Gao, Dongxu; Wu, Meifang; Wang, Chonggang; Wang, Yuanchuan; Zuo, Zhenghong

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans. PMID:26349946

  16. Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Zelmina Lubovac-Pilav

    Full Text Available Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12, this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc. and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.. Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.

  17. Risk Analysis of Acute Or Chronic Exposure to Arsenic of the Inhabitants in a District of Buenos Aires, Argentina

    Directory of Open Access Journals (Sweden)

    Cristina Vázquez

    2016-09-01

    Full Text Available The arsenic occurrence in the water constitutes a serious world health concern due to its toxicity. Depending on the intensity and duration of exposure, this element can be acutely lethal or may have a wide range of health effects in humans and animals. In Argentina, the origin of arsenic is mainly natural, and related to different geological processes. The Argentinean concern about arsenic and its influence on human health dates back to the previous century. The disease ascribed to arsenic contamination was called ‘chronic regional endemic hydroarsenism’. It is produced by the consumption of water with high levels of this element. In our study, we focused in La Matanza district, a very populated site in the Buenos Aires Province. An increasing concern of the inhabitants of the area regarding health problems was detected. In order to establish a full view of arsenic exposure in the area, several matrices and targets were analyzed. As matrices, water and soil samples were analyzed. As targets, canine and human hair was studied. The aim of this study was to investigate acute and chronically exposure to arsenic of La Matanza inhabitants.

  18. Chronic copper exposure and fatty acid composition of the amphipod Dikerogammarus villosus: Results from a field study

    International Nuclear Information System (INIS)

    Field study allows assessment of long-term effects on fatty acid (FA) composition of organisms under chronic exposure to metals. One expected effect of copper is peroxidation of lipids and essentially polyunsaturated fatty acids (PUFA). FA analysis was established for the amphipod Dikerogammarus villosus subjected to different degrees of copper exposure (4-40 μg Cu L-1). A previous study in our team showed that this species regulates its body Cu concentration (106-135 mg Cu kg-1 dry weight). Despite the high capacity of bioaccumulation, the absence of a correlation between copper concentration in D. villosus and water prevents its use as bioindicator of copper pollution. Both sexes from the most polluted site showed the lowest total FA content, but the highest PUFA percent, mainly of the long-chained variety (C20-C22). Mechanisms leading to the prevention of lipid peroxidation in this species were discussed (metallothioneins and intracellular granules) and proposed with support from literature data. - Under chronic copper exposure, Dikerogammarus villosus loses in total fatty acids content but increases its essential ω3 and ω6 PUFA percent

  19. Chronic copper exposure and fatty acid composition of the amphipod Dikerogammarus villosus: Results from a field study

    Energy Technology Data Exchange (ETDEWEB)

    Maazouzi, Chafik [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: maazouzi@univ-metz.fr; Masson, Gerard [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: masson1@univ-metz.fr; Izquierdo, Maria Soledad [Grupo de Investigacion en Acuicultura, ULPGC and ICCM, P.O. Box 56, 35200 Telde, Las Palmas de Gran Canaria (Spain)], E-mail: mizquierdo@dbio.ulpgc.es; Pihan, Jean-Claude [Universite de Metz, Laboratoire Interactions Ecotoxicologie Biodiversite Ecosystemes (LIEBE), CNRS UMR 7146, Avenue General Delestraint, 57070 Metz (France)], E-mail: pihan@univ-metz.fr

    2008-11-15

    Field study allows assessment of long-term effects on fatty acid (FA) composition of organisms under chronic exposure to metals. One expected effect of copper is peroxidation of lipids and essentially polyunsaturated fatty acids (PUFA). FA analysis was established for the amphipod Dikerogammarus villosus subjected to different degrees of copper exposure (4-40 {mu}g Cu L{sup -1}). A previous study in our team showed that this species regulates its body Cu concentration (106-135 mg Cu kg{sup -1} dry weight). Despite the high capacity of bioaccumulation, the absence of a correlation between copper concentration in D. villosus and water prevents its use as bioindicator of copper pollution. Both sexes from the most polluted site showed the lowest total FA content, but the highest PUFA percent, mainly of the long-chained variety (C20-C22). Mechanisms leading to the prevention of lipid peroxidation in this species were discussed (metallothioneins and intracellular granules) and proposed with support from literature data. - Under chronic copper exposure, Dikerogammarus villosus loses in total fatty acids content but increases its essential {omega}3 and {omega}6 PUFA percent.

  20. Impact of chronic cadmium exposure at environmental dose on escape behaviour in sea bass (Dicentrarchus labrax L.; Teleostei, Moronidae)

    International Nuclear Information System (INIS)

    The effect of chronic exposure to a low concentration (0.5 μg l-1) of cadmium ions was investigated on escape behaviour of sea bass, Dicentrarchus labrax, using video analysis. Observations were also performed on the microanatomy of lateral system neuromasts. When fish were exposed for 4 h per day over 8 days to the cadmium ions, most of both types of neuromasts observed remained intact. However, some of them presented damaged sensory maculae. Whereas before cadmium exposure, fish responded positively to nearly all the lateral system stimulations, after exposure they decreased by about 10% their positive responses to stimulations. From the 15th day after the beginning of cadmium exposure, neuromasts presented progressively less damage, cadmium accumulation in gills and scales decreased significantly and fish escape behaviour had recovered. This study presents a new concept in ecotoxicology: using behavioural change to reveal the effects of pollution levels, scarcely detectable by currently used techniques (physiological responses). - Cadmium exposure involved a significant bioaccumulation in fish scales, slight damage to the lateral line system and a significant decrease in fish escape behaviour

  1. Chronic pain relief after the exposure of nitrous oxide during dental treatment: longitudinal retrospective study

    Directory of Open Access Journals (Sweden)

    Francisco Moreira Mattos Júnior

    2015-07-01

    Full Text Available The objective was to investigate the effect of nitrous/oxygen in chronic pain. Seventy-seven chronic pain patients referred to dental treatment with conscious sedation with nitrous oxide/oxygen had their records included in this research. Data were collected regarding the location and intensity of pain by the visual analogue scale before and after the treatment. Statistical analysis was performed comparing pre- and post-treatment findings. It was observed a remarkable decrease in the prevalence of pain in this sample (only 18 patients still had chronic pain, p < 0.001 and in its intensity (p < 0.001. Patients that needed fewer sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may be a tool to be used in the treatment of chronic pain, and future prospective studies are necessary to understand the underlying mechanisms and the effect of nitrous oxide/oxygen in patients according to the pain diagnosis and other characteristics.

  2. Pulmonary sensitivity to ozone exposure in sedentary versus chronically trained, female rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Pulmonary effects to ozone with rats that have chronically exercised or have been continuously sedentary. Also includes body composition of both groups throughout...

  3. Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide

    Energy Technology Data Exchange (ETDEWEB)

    Nutter, Thomas J., E-mail: tnutter@dental.ufl.edu; Cooper, Brian Y., E-mail: bcooper@dental.ufl.edu

    2014-06-15

    Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were

  4. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    Energy Technology Data Exchange (ETDEWEB)

    Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

    2015-03-01

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  5. MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

    International Nuclear Information System (INIS)

    Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

  6. Chronic Exposure to Beta-Blockers Attenuates Inflammation and Mucin Content in a Murine Asthma Model

    OpenAIRE

    Nguyen, Long P.; Omoluabi, Ozozoma; Parra, Sergio; Frieske, Joanna M.; Clement, Cecilia; Ammar-Aouchiche, Zoulikha; Ho, Samuel B.; Ehre, Camille; Kesimer, Mehmet; Knoll, Brian J.; Tuvim, Michael J; Dickey, Burton F.; Bond, Richard A.

    2007-01-01

    Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers de...

  7. Chronic exposure of ecosystems and public to elements in trace contributions

    International Nuclear Information System (INIS)

    The needs in radiation protection come towards the question of chronic contaminations by trace elements or radioactive compounds. The chronicity induces to take into account a whole of redistribution mechanisms more important than the only ways of the most direct transfer. In the case of environment, that is going to become one of the way of public contamination is a target to protect, the important work is to link the contamination situation to eventual consequences on the ecosystems situation. (N.C.)

  8. Chronic exposure to perfluorinated compounds: Impact on airway hyperresponsiveness and inflammation

    OpenAIRE

    Ryu, Min H.; Jha, Aruni; Ojo, Oluwaseun O.; Mahood, Thomas H.; Basu, Sujata; Detillieux, Karen A.; Nikoobakht, Neda; Wong, Charles S.; Loewen, Mark; Allan B Becker; Halayko, Andrew J.

    2014-01-01

    Emerging epidemiological evidence reveals a link between lung disease and exposure to indoor pollutants such as perfluorinated compounds (PFCs). PFC exposure during critical developmental stages may increase asthma susceptibility. Thus, in a murine model, we tested the hypothesis that early life and continued exposure to two ubiquitous household PFCs, perfluorooctanoic acid (PFOA) and perflurooctanesulfonic acid (PFOS), can induce lung dysfunction that exacerbates allergen-induced airway hype...

  9. INDUCTION OF CHRONIC KIDNEY FAILURE IN A LONG-TERM PERITONEAL EXPOSURE MODEL IN THE RAT: EFFECTS ON FUNCTIONAL AND STRUCTURAL PERITONEAL ALTERATIONS

    NARCIS (Netherlands)

    F. Vrtovsnik; A. Coester; D. Lopes-Barreto; D.R. de Waart; A. van der Wal; D.G. Struijk; R. Krediet; M. Zweers

    2010-01-01

    Background: A long-term peritoneal exposure model has been developed in Wistar rats. Chronic daily exposure to 3.86% glucose based, lactate buffered, conventional dialysis solutions is possible for up to 20 weeks and induces morphological abnormalities similar to those in long-term peritoneal dialys

  10. Acute Ethanol Exposure Prevents PMA-mediated Augmentation of N-methyl-d-aspartate Receptor Function in Primary Cultured Cerebellar Granule Cells

    OpenAIRE

    Reneau, Jason; Reyland, Mary E.; Popp, R. Lisa

    2011-01-01

    Many intracellular proteins and signaling cascades contribute to the ethanol sensitivity of native N-methyl-d-aspartate receptors (NMDARs). One putative protein is the serine / threonine kinase, Protein kinase C (PKC). The purpose of this study was to assess if PKC modulates the ethanol sensitivity of native NMDARs expressed in primary cultured cerebellar granule cells (CGCs). With the whole-cell patch-clamp technique, we assessed if ethanol inhibition of NMDA-induced currents (INMDA) (100 μM...

  11. The implications of re-analysing radiation-induced leukaemia in atomic bomb survivors: risks for acute and chronic exposures are different

    International Nuclear Information System (INIS)

    Implications of risk estimates, as required for practical radiation protection purposes, were explored through a preliminary re-analysis of leukaemia in the Japanese atomic bomb survivors using a biologically based cancer model. The calculations for the risks posed for contracting leukaemia pointed to important differences between low-dose-rate ('chronic') and high-dose-rate ('acute') exposures. For example, the risks caused by long-term ('chronic') exposures are calculated to be substantially lower than those for 'acute' exposures. In view of these model predictions the results of epidemiological studies are discussed. (author)

  12. Impact of water-accommodated fractions of crude oil on Atlantic cod, Gadus morhua following chronic exposure

    International Nuclear Information System (INIS)

    This study examined the long-term effects of hydrocarbon exposure on the gonadal development of fish. Mature Atlantic cod (Gadus morhua) were exposed to low concentrations of water accommodated fractions (WAFs) of polycyclic aromatic hydrocarbons (PAHs) in an ambient flowthrough seawater system. Some PAH-exposed cod groups were depurated afterwards for 38 to 287 days. Mortality was rare, and external lesions occurred only in the PAH-exposed groups. The gonado-somatic index revealed that gonadal development was disrupted in both sexes and spawning and spermiation was delayed in the 33 depurated PAH-groups. The findings indicate that chronic exposure to WAFs in the water column may have an adverse effect on reproduction in Atlantic cod.

  13. Effects of chronic produced water exposure on the expression of some immune-related genes of juvenile Atlantic cod

    International Nuclear Information System (INIS)

    This study assessed the impacts of exposure to processed water produced by offshore oil operators on immune-related genes of juvenile Atlantic cod exposed to processed water for a period of 22 weeks. The study investigated the influence of processed water concentrations on growth parameters; food consumption; plasma cortisol; respiratory burst activity (RB); and mRNA expression. The study showed that the RB of circulating leukocytes was significantly elevated. Significant up-regulation of the mRNA expression of microglobulin, immunoglobulin light chain, and interleukins was observed in some fish. The down-regulation of the interferon stimulated gene was also observed. The study indicated that chronic exposure to significant amounts of processed water causes modulations of the immune system of juvenile Atlantic cod.

  14. Environmental benefits of ethanol

    International Nuclear Information System (INIS)

    The environmental benefits of ethanol blended fuels in helping to reduce harmful emissions into the atmosphere are discussed. The use of oxygenated fuels such as ethanol is one way of addressing air pollution concerns such as ozone formation. The state of California has legislated stringent automobile emissions standards in an effort to reduce emissions that contribute to the formation of ground-level ozone. Several Canadian cities also record similar hazardous exposures to carbon monoxide, particularly in fall and winter. Using oxygenated fuels such as ethanol, is one way of addressing the issue of air pollution. The net effect of ethanol use is an overall decrease in ozone formation. For example, use of a 10 per cent ethanol blend results in a 25-30 per cent reduction in carbon monoxide emissions by promoting a more complete combustion of the fuel. It also results in a 6-10 per cent reduction of carbon dioxide, and a seven per cent overall decrease in exhaust VOCs (volatile organic compounds). The environmental implications of feedstock production associated with the production of ethanol for fuel was also discussed. One of the Canadian government's initiatives to address the climate change challenge is its FleetWise initiative, in which it has agreed to a phased-in acquisition of alternative fuel vehicles by the year 2005. 9 refs

  15. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Science.gov (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Carr, Michael; Martens, Kris M; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

    2016-01-01

    Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI. PMID:26784694

  16. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury

    International Nuclear Information System (INIS)

    OBJECTIVES: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency

  17. Evaluation of the effect of chronic exposure to 137Cesium on sleep-wake cycle in rats

    International Nuclear Information System (INIS)

    Since the Chernobyl accident, the most significant problem for the population living in the contaminated areas is chronic exposure by ingestion of radionuclides, notably 137Cs, a radioactive isotope of cesium. It can be found in the whole body, including the central nervous system. The present study aimed to assess the effect of 137Cs on the central nervous system and notably on open-field activity and the electroencephalographic pattern. Rats were exposed up to 90 days to drinking water contaminated with 137Cs at a dosage of 400 Bq kg-1, which is similar to that ingested by the population living in contaminated territories. At this level of exposure, no significant effect was observed on open-field activity. On the other hand, at 30 days exposure, 137Cs decreased the number of episodes of wakefulness and slow wave sleep and increased the mean duration of these stages. At 90 days exposure, the power of 0.5-4 Hz band of 137Cs-exposed rats was increased in comparison with controls. These electrophysiological changes may be due to a regional 137Cs accumulation in the brain stem. In conclusion, the neurocognitive effects of 137Cs need further evaluation and central disorders of population living in contaminated territories must be considered

  18. Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

    International Nuclear Information System (INIS)

    Introduction: Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN). Methods: The present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period. Results: In nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05). Conclusions: This study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.

  19. Chronic exposure to perfluorooctane sulfonate induces behavior defects and neurotoxicity through oxidative damages, in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Na Chen

    Full Text Available Perfluorooctane sulfonate (PFOS is an emerging persistent pollutant which shows multiple adverse health effects. However, the neurotoxicity of PFOS and its mechanisms have not been fully elucidated. Using a combination of in vivo and in vitro methods, the present study provides a detailed description of PFOS-induced neurotoxicity. Results showed that the median lethal concentration of PFOS was 2.03 mM in Caenorhabditis elegans for 48 h exposure. 20 µM PFOS caused decrease of locomotor behaviors including forward movement, body bend and head thrash. Additionally, PFOS exposure reduced chemotaxis index of C. elegans, which indicates the decline of chemotaxis learning ability. Using green fluorescent protein (GFP labelled transgenic strains, we found that PFOS caused down-regulated expression of a chemoreceptor gene, gcy-5, in ASE chemosensory neurons, but did not affect cholinergic neurons and dopaminergic neurons. In SH-SY5Y cells, 48 h exposure to 25 µM and 50 µM PFOS induced cell damage, apoptosis and the reactive oxygen species (ROS generation. PFOS caused significant increases of lipid peroxidation and superoxide dismutase activity, but an actual decrease of glutathione peroxidase activity. Furthermore, antioxidant N-acetylcysteine rescued cells from PFOS-induced apoptosis via blocking ROS. Our results demonstrate that chronic exposure to PFOS can cause obvious neurotoxicity and behavior defects. Oxidative damage and anti-oxidative deficit are crucial mechanisms in neurotoxicity of PFOS.

  20. Aphrodisiac Activity and Curative Effects of Pedalium Murex (L) Against Ethanol Induced Infertility in Male Rats

    OpenAIRE

    BALAMURUGAN, Gunasekaran; P. Muralidharan; POLAPALA, Satyanarayana

    2010-01-01

    It has been suggested that chronic ethanol exposure may result in testicular damage and infertility in males. Petroleum ether extract of Pedalium murex, family Pedaliaceae (PEPM), is evaluated in this study for its ability to increase aphrodisiac activity and to cure ethanol induced germ cell damage and infertility in male rat models. Doses of 200 and 400 mg/kg of PEPM showed a significant increase (P < 0.01, P < 0.001) in mating and mounting behaviour. The effect on fertility factors s...

  1. Effect of chronic lead exposure on kidney function in male and female rats: determination of a lead exposure biomarker.

    Science.gov (United States)

    Ghorbe, F; Boujelbene, M; Makni-Ayadi, F; Guermazi, F; Kammoun, A; Murat, J; Croute, F; Soleilhavoup, J P; El-Feki, A

    2001-12-01

    Several cytotoxic chemical pollutants inducing peroxidative damages are liable to induce kidney failure. Among these pollutants we find heavy metals such as: lead, nickel, cadmium, vanadium and mercury. Lead is one of the most dangerous metals because it is widely spread in the environment, and because it may be a source of several nervous diseases. The aim of this study is to provide evidence concerning the effect of this metal on the renal function and to try to determine a storage corner in the organism which serves as an indicator of a lead intoxication. Lead acetate was administered by oral route in the drinking water to adult rats aged three months at the rate of 0.3% (P1) and 0.6% (P2). Reference rats received distilled water to drink under the same conditions. The treatment continued for 15, 30, 45, 60 and 90 days. The creatinemia, uremia, glycemia and creatinuria are determined by colorimetric techniques. Lead concentration in blood as well as the lead content of the tail are determined by atomic absorption after nitroperchloric mineralization at the liquid stage. The results showed an increase of creatinemia on the 30th day of the experiment for both sexes in (P1 and P2). The same happened for ureamia. The increase of these two parameters would indicate a renal deficiency which is confirmed by a decrease of creatinuria and urinary pH observed mainly on and after the 45th day of the experiment. An increase of the renal relative weight was noticed in P1 and P2 on the 30th day of the treatment. The determination of the concentration of lead in the blood shows that this factor increases among treated subjects in a constant way, independently of the dose and the duration of the treatment. Nevertheless, the rate increase of lead in the tail seems to be dose-dependent. In conclusion, lead administered by oral route causes a renal deficiency to the rat without distinction between males and females. In addition, the tail seems to be a reliable exposure biomarker

  2. Acute and chronic effects of pulse exposure of Daphnia magna to dimethoate and pirimicarb.

    Science.gov (United States)

    Andersen, Tobias Henrik; Tjørnhøj, Rikke; Wollenberger, Leah; Slothuus, Tina; Baun, Anders

    2006-05-01

    Short-term (Daphnia magna exposed to pulses of 0.5 to 8 h in duration. During a 21-d postexposure observation period, the following parameters were monitored: Mortality, mobility, day for first offspring, animal size, weight of offspring and adults, and number of offspring produced. In general, animals exposed to a single pulse of dimethoate or pirimicarb regained mobility after 24 to 48 h in clean media. Animals exposed to repeated pulses of dimethoate did not recover mobility during a 48-h postexposure observation period, and mortality was significantly increased. Animals exposed to two pulses of pirimicarb showed less recovery of mobility compared with those exposed to one pulse. Exposure of D. magna to 30 mg/L of dimethoate or 100 microg/L of pirimicarb for 2 to 6 h resulted in a significant reduction in the number of offspring and in the average weight of offspring. The average body length was reduced after pulse exposure to 30 mg/L of dimethoate for 3 h or 70 microg/L of pirimicarb for 4 h, and these exposure concentrations caused a delay in the day for first offspring at exposure durations of 2 to 6 h. The most important new findings in the present study are that short-term (<4 h) pulse exposure of neonates to acetylcholinesterase-inhibiting pesticides caused reproductive damage in D. magna and that repeated-pulse exposure significantly increased mortality in animals that apparently had recovered after a single-pulse exposure. PMID:16704047

  3. The Association between Chronic Arsenic Exposure and Hypertension: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Tanvir Abir

    2012-01-01

    Full Text Available Background. There is inconclusive evidence from cross-sectional and cohort studies that arsenic exposure is a risk factor involved in the development of hypertension. Methods. A database search, using several keywords, was conducted to identify relevant studies. Separate odds ratio estimates for arsenic exposure with concentration only and arsenic exposure with duration, including biomarker, were extracted from studies that met all inclusion criteria. The extracted odds ratios (OR comparing the highest exposure categories with the lowest in each study were pooled using the random effects methods of meta-analysis. Heterogeneity of odds ratios in the included studies were analyzed using I2 statistics. Results. Eight studies were analyzed. Using the exposure as arsenic concentration in the drinking water, the OR estimate was 1.9 (95% CI: 1.2–3.0, with the I2 = 92%, while using the exposure as concentration and duration, the OR estimate was 1.4 (95% CI: 0.95–2.0 with the I2 = 80%. Meta-regression was done and the quality of exposure measurement was found to be significantly associated with the effect measure. For a one unit increase in the score from exposure assessment, the odds ratio decreased by 6%. No publication bias was evident. The only major weaknesses of this study were heterogeneity across studies and small sample size. Conclusions. The study findings provide limited evidence for a relationship between arsenic and hypertension. In summary, the relationship between arsenic exposure and hypertension is still inconclusive and needs further validation through prospective cohort studies.

  4. Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat.

    Science.gov (United States)

    Srivastava, Vinod K; Hiney, Jill K; Dees, W Les

    2011-03-01

    Glial-derived transforming growth factor alpha (TGFα) activates the erbB1/erbB2 receptor complex on adjacent glial cells in the medial basal hypothalamus (MBH). This receptor activation stimulates the synthesis and release of prostaglandin-E(2) (PGE(2)) from the glial cells, which then induces the release of prepubertal luteinizing hormone-releasing hormone (LHRH) secretion from nearby nerve terminals; thus, showing the importance of glial-neuronal communications at the time of puberty. Ethanol (EtOH) is known to cause depressed prepubertal LHRH secretion and delayed pubertal development. In this study, we assessed whether short-term EtOH exposure could alter the hypothalamic glial to glial signaling components involved in prepubertal PGE(2) secretion. Immature female rats began receiving control or EtOH diets beginning when 27 days old. The animals were killed by decapitation after 4 and 6 days of treatment and confirmed to be in the late juvenile stage of development. Blood and brain tissues were collected for gene, protein, and hormonal assessments. Real-time polymerase chain reaction (PCR) analysis demonstrated that EtOH did not affect basal levels of erbB1 gene expression in the MBH. Expression of total erbB1 protein was also unaffected; however, the EtOH caused suppressed phosphorylation of erbB1 protein in the MBH at both 4 and 6 days (P<.01) as revealed by Western blotting. Phosphorylation and total protein levels of erbB2 receptor were not affected by EtOH exposure. Because this receptor is critical for PGE(2) synthesis/release, which mediates the secretion of LHRH, we assessed whether in vivo EtOH exposure could affect the release of PGE(2). EtOH exposure for 6 days suppressed (P<.01) basal levels of PGE(2) released into the medium. The effects of 4- and 6-day EtOH exposure on gene and protein expressions of TGFα, an upstream component in the activation of erbB1/erbB2, were also studied. The levels of TGFα mRNA were increased markedly at 4 days (P<.001

  5. Spatial variations in estimated chronic exposure to traffic-related air pollution in working populations: A simulation

    Directory of Open Access Journals (Sweden)

    Cloutier-Fisher Denise

    2008-07-01

    Full Text Available Abstract Background Chronic exposure to traffic-related air pollution is associated with a variety of health impacts in adults and recent studies show that exposure varies spatially, with some residents in a community more exposed than others. A spatial exposure simulation model (SESM which incorporates six microenvironments (home indoor, work indoor, other indoor, outdoor, in-vehicle to work and in-vehicle other is described and used to explore spatial variability in estimates of exposure to traffic-related nitrogen dioxide (not including indoor sources for working people. The study models spatial variability in estimated exposure aggregated at the census tracts level for 382 census tracts in the Greater Vancouver Regional District of British Columbia, Canada. Summary statistics relating to the distributions of the estimated exposures are compared visually through mapping. Observed variations are explored through analyses of model inputs. Results Two sources of spatial variability in exposure to traffic-related nitrogen dioxide were identified. Median estimates of total exposure ranged from 8 μg/m3 to 35 μg/m3 of annual average hourly NO2 for workers in different census tracts in the study area. Exposure estimates are highest where ambient pollution levels are highest. This reflects the regional gradient of pollution in the study area and the relatively high percentage of time spent at home locations. However, for workers within the same census tract, variations were observed in the partial exposure estimates associated with time spent outside the residential census tract. Simulation modeling shows that some workers may have exposures 1.3 times higher than other workers residing in the same census tract because of time spent away from the residential census tract, and that time spent in work census tracts contributes most to the differences in exposure. Exposure estimates associated with the activity of commuting by vehicle to work were

  6. Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease

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    Weeks Jennifer

    2008-06-01

    Full Text Available Abstract Background The emergence and continuing spread of Chronic Wasting Disease (CWD in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally. In 2005, CWD spread for the first time from the Midwest to more densely populated regions of the East Coast. As a result, a large cohort of individuals attending a wild game feast in upstate New York were exposed to a deer that was subsequently confirmed positive for CWD. Methods Eighty-one participants who ingested or otherwise were exposed to a deer with chronic wasting disease at a local New York State sportsman's feast were recruited for this study. Participants were administered an exposure questionnaire and agreed to follow-up health evaluations longitudinally over the next six years. Results Our results indicate two types of risks for those who attended the feast, a Feast Risk and a General Risk. The larger the number of risk factors, the greater the risk to human health if CWD is transmissible to humans. Long-term surveillanc