Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

September 2012

Volume 32, Issue 9

Pages 643–749

  1. Review Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. epigenetic targets of some toxicologically relevant metals: a review of the literature (pages 643–653)

      Tsu-Fan Cheng, Supratim Choudhuri and Kristi Muldoon-Jacobs

      Version of Record online: 15 FEB 2012 | DOI: 10.1002/jat.2717

      The current explosion of research on epigenetics, and the increasing reports documenting effects of various environmental factors on DNA methylation, chromatin modification, and expression of small non-coding RNAs have expanded the scope of research in molecular toxicology as well as the etiology of various diseases. The present review briefly discusses various molecular mechanisms of epigenetic regulation of gene expression, and expands the discussion with examples of heavy metal-induced epigenetic changes and concurrent alterations of gene expression.

  2. Research Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Effect of fluorescent whitening agent on the transcription of cell damage-related genes in zebrafish embryos (pages 654–661)

      Hyun Jung, Seung-Hyeok Seok, Ju-Hee Han, Tamer Said Abdelkader, Tae-Hyoun Kim, Seo-Na Chang, Ae-Sun Ko, Seung-Kyu Choi, Cho-Rong Lee, Ji-Eun Seo, Soo-Hyun Byun, Jung-A Kim and Jae-Hak Park

      Version of Record online: 2 MAY 2011 | DOI: 10.1002/jat.1665

      7-Diethylamino-4-methylcoumarin (DEMC) is one of fluorescent whitening agents (FWAs) and DEMC-using solutions flow in river and ocean. In this study, we used wild type zebrafish to research about toxicity of DEMC in aquatic environment. High concentration DEMC-treated groups showed several development toxic effects - low survival, hatching and heart rates and high malformations rates. Moreover, DEMC alteration effect of gene expression which related oxidative stress, mitochondrial metabolism and apoptosis in zebrafish embryos.

    2. Protective effects of enalapril in streptozotocin-induced diabetic rat: studies of DNA damage, apoptosis and expression of CCN2 in the heart, kidney and liver (pages 662–672)

      S. Kushwaha, A. Vikram and G. B. Jena

      Version of Record online: 18 MAR 2011 | DOI: 10.1002/jat.1670

      The hyperglycemic condition in diabetes leads to oxidative stress and tissue injury. Present study was aimed to investigate the possible protective effects of enalapril, a non-thiol angiotensin-converting enzyme inhibitor, in the development of diabetes associated fibrosis and DNA damage in rat. The endpoints of evaluation include the DNA damage, apoptosis and the expression of profibrotic marker CCN2. Results concluded that enalapril attenuates the DNA damage, apoptosis and the expression of CCN2 in the heart, kidney and liver of diabetic rat.

    3. Calibration and validation of a physiologically based model for soman intoxication in the rat, marmoset, guinea pig and pig (pages 673–686)

      Kaizhen Chen and Kok-Yong Seng

      Version of Record online: 24 MAR 2011 | DOI: 10.1002/jat.1671

      A physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed for soman intoxication in the rat, marmoset, guinea pig and pig. The model was first calibrated for the rat, then validated in the marmoset, guinea pig and pig. The model-predicted and experimentally-measured time profiles of soman concentration, and AChE inhibition and recovery matched adequately. The results suggest that the model can potentially be used for predicting soman pharmacokinetics and pharmacodynamics in other species including human.

    4. Toxicity of methyl tertiary-butyl ether (MTBE) following exposure of Wistar Rats for 13 weeks or one year via drinking water (pages 687–706)

      Edilberto Bermudez, Gabrielle Willson, Horace Parkinson and Darol Dodd

      Version of Record online: 24 MAR 2011 | DOI: 10.1002/jat.1674

      Exposure of Wistar rats to MTBE in the drinking water resulted in minimal exposure-related effects including limited renal changes in male rats suggestive of α2u-globulin nephropathy following 13 weeks of exposure and an exacerbation of CPN in males at the end of one year of exposure.

    5. The effect of methylmercury exposure on early central nervous system development in the zebrafish (Danio rerio) embryo (pages 707–713)

      S. A. Hassan, E. A. Moussa and L. C. Abbott

      Version of Record online: 21 MAR 2011 | DOI: 10.1002/jat.1675

      Zebrafish embryos (ZFEs) were exposed 24 hours to one of nine concentrations of methylmercury (0 to 1000 parts per billion (μg/L)) starting at 6 hours post-fertilization. No abnormalities were observed in ZFEs exposed to 5 μg/L methylmercury. Hatching was delayed in ZFEs exposed to methylmercury concentrations of 50 μg/L or higher. ZFEs exposed to more than 200 μg/L methylmercury exhibited 100% mortality. Neural tube cell proliferation was significantly decreased in embryos exposed to 10, 50, and 80 μg/L methylmercury.

    6. Protective effect of apocynin on antimycin A-induced cell damage in osteoblastic MC3T3-E1 cells (pages 714–721)

      Eun Mi Choi and Young Soon Lee

      Version of Record online: 2 MAY 2011 | DOI: 10.1002/jat.1689

      In the present study, we investigated the protective effects of apocynin on antimycin A (AMA)-induced toxicicy in osteoblastic MC3T3-E1 cells. Pretreatment with apocynin significantly reduced AMA-induced cell damage by preventing mitochondrial membrane potential dissipation, complex IV inactivation, ATP loss, [Ca2+]i elevation, and oxidative stress. Apocynin also induced the activation of PI3K, Akt, and CREB inhibited by AMA.

    7. Effects of usnic acid exposure on human hepatoblastoma HepG2 cells in culture (pages 722–730)

      Saura C. Sahu, Margaret Amankwa-Sakyi, Michael W. O'Donnell Jr and Robert L. Sprando

      Version of Record online: 23 SEP 2011 | DOI: 10.1002/jat.1721

      Usnic acid is a constituent of some dietary supplements used for weight loss. Its exposure resulted in increased P450 activity, cytotoxicity, oxidative stress and mitochondrial dysfunction in cultured human liver HepG2 cells. A pathway-focused gene expression analysis resulted in marked up-regulation of three genes CCL21, CCNC and UGT1A4 as well as the down-regulation of three genes CSF2, CYP7A1 and CYP2E1 in the usnic acid-treated cells compared with the vehicle controls. This study demonstrated the toxicity of usnic acid in human liver HepG2 cells suggesting an oxidative mechanism of action.

    8. Evaluation of glutathione s-transferase as toxicity indicator for roxarsone and arsanilic acid in Eisenia fetida (pages 731–738)

      Muhammad Rizwan-ul-Haq, Zeng Zhenling, Sun Yongxue and Xiong Wenguang

      Version of Record online: 9 MAR 2012 | DOI: 10.1002/jat.2726

      Glutathione-S-transferase has been evaluated as a potential biomarker during this study against the chemicals like roxarsone and arsanilic acid which pollute the environment by degrading into arsenic. During this study, full-length gene sequence of GST, having the size 984 bp was achieved from Eisenia fetida. The protein has a computed molecular mass of 23.56 kDa and a predicted isoelectric point of 9.92. Enzyme analysis and QRT-PCR revealed significant differences in activities in response to roxarsone and arsanilic acid treatments as compared to control treatment.

    9. Interactive toxicity of usnic acid and lipopolysaccharides in human liver HepG2 cells (pages 739–749)

      Saura C. Sahu, Michael W. O'Donnell Jr and Robert L. Sprando

      Version of Record online: 9 JUL 2012 | DOI: 10.1002/jat.2768

      Usnic acid (UA), a natural botanical product, is a constituent of some dietary supplements used for weight loss. Lipopolysaccharide (LPS) is a potential contaminant of food. In this study they showed no effect individually on the human hepatoblastoma HepG2 cells at low nontoxic concentrations. However, their simultaneous mixed exposure at the same low nontoxic concentrations resulted in increased cellular cytotoxicity, oxidative stress and mitochondrial injury. The pathway-focused gene expression analysis resulted in altered expression of several genes. Most altered gene expressions induced by the simultaneous mixed exposure were different from those induced by the individual constituents. The genes affected by the mixture were not modulated by either UA or LPS. The results of the present study suggests that the interactions of low nontoxic concentrations of UA and LPS produce toxicity in HepG2 cells.

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