Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

March 2009

Volume 29, Issue 2

Pages 91–182

  1. Reviews

    1. Top of page
    2. Reviews
    3. Research Articles
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      NF-κB in liver diseases: a target for drug therapy (pages 91–100)

      Pablo Muriel

      Article first published online: 20 OCT 2008 | DOI: 10.1002/jat.1393

      There are five nuclear factor-κB (NF-κB) transcription factors with important roles in innate immunity, liver inflammation, fibrosis, and apoptosis prevention. Several inhibitors of NF-κB have demonstrated antinecrotic, anticholestatic, antifibrotic and anticancer activities in the liver. However, activation of this factor during the resolution of inflammation is associated with the production of antiinflammatory molecules. Therefore, basic understanding on the function of the diverse NF-κB factors is urgently needed in different physiological and pathological conditions.

  2. Research Articles

    1. Top of page
    2. Reviews
    3. Research Articles
    1. Effects of choline-deprivation on paracetamol- or phenobarbital-induced rat liver metabolic response (pages 101–109)

      Maria Konstandi, Dimitrios Segos, Panagiota Galanopoulou, Stamatios Theocharis, Apostolos Zarros, Matti A. Lang, Marios Marselos and Charis Liapi

      Article first published online: 16 SEP 2008 | DOI: 10.1002/jat.1386

      Various pathophysiological states have been linked to choline deprivation (CD). The aim of the present study was to determine the effect of CD upon biochemical, histological and metabolic alterations induced by paracetamol (ACET) or phenobarbital (PB) (drugs that affect hepatic functional integrity and various drug metabolising systems via distinct mechanisms). For this purpose, male Wistar rats that were fed with standard rodent chow or underwent dietary CD, received ACET or PB. Our findings suggest that CD has a significant impact on the hepatic metabolic functions, and in particular on those related to drug metabolism. Thus, CD may modify drug effectiveness and toxicity, as well as drug-drug interactions, particularly those related to ACET and PB.

    2. Metabolic significance of bisphenol A-induced oxidative stress in rat urine measured by liquid chromatography–mass spectrometry (pages 110–117)

      Sung-Hee Cho, Man Ho Choi, Oh Seung Kwon, Won-Yong Lee and Bong Chul Chung

      Article first published online: 4 NOV 2008 | DOI: 10.1002/jat.1387

      The liquid chromatographic-mass spectrometric analysis of 14 nucleoside was investigated in rat urine to evaluate bisphenol A (BPA)-induced oxidative stress after intraperitoneally injection of BPA into rats. Increased levels of 5-hydroxymethyl-2'-deoxyuridine (P < 0.01 in 1st, P < 0.005 in 2nd, P < 0.001 in 3rd, and P < 0.01 in 4th day) and 8-hydroxy-2'-deoxyguanosine (P < 0.005 in 2nd, P < 0.001 in 3rd, and P < 0.001 in 4th day) could explain the metabolic changes for physiological responses.

    3. Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice (pages 118–125)

      Rebecca Jane Dearman, Catherine Jean Betts, Lorna Beresford, Laura Bailey, Helen Theresa Caddick and Ian Kimber

      Article first published online: 24 SEP 2008 | DOI: 10.1002/jat.1388

      Plasticizers such as butyl benzyl phthalate (BBP) have been implicated as adjuvants, potentially contributing to the rise in IgE-mediated allergies. The impact of BBP on responses induced in BALB/c mice by the allergen ovalbumin has been examined. Topical administration of BBP was without impact on IgE antibody, although same site treatment with high doses caused small increases in IgG1 antibody, an IgE surrogate, suggesting that environmental doses of phthalate are unlikely to be contributing to the increased incidence of allergy.

    4. Dietary fats altered nephrotoxicity profile of methylmercury in rats (pages 126–140)

      Xiaolei Jin, Eric Lok, Don Caldwell, Rudi Mueller, Kamla Kapal, Virginia Liston, Stan Kubow, Hing Man Chan and Rekha Mehta

      Article first published online: 29 SEP 2008 | DOI: 10.1002/jat.1389

      Effects of dietary soy oil, seal oil, docosahexaenoic acid, fish oil and lard on kidney nephrotoxicity of methylmercury were investigated in rats. Regardless of the diets used, MeHg induced numerous significant renal and systemic changes after two weeks of exposure, pointing to a nephrotic syndrome-like renal toxicity. None of the diets used completely eliminated MeHg-induced renal injury; however, they altered the nephrotoxicity profiles of MeHg, suggesting that multiple parameters should be examined to compare MeHg toxicity under different dietary backgrounds.

    5. Inter-laboratory comparisons of assessment of the allergenic potential of proteins in mice (pages 141–148)

      C. Herouet-Guicheney, H. Aldemir, R. Bars, D. de Barbeyrac, P. Kennel, D. Rouquié, B. U. Stahl, I. Kimber and R. J. Dearman

      Article first published online: 20 OCT 2008 | DOI: 10.1002/jat.1391

      BALB/c mice were exposed to a range of doses of peanut agglutinin or ovalbumin, allergenic proteins of peanut and hen's egg, respectively, in two independent laboratories. The findings demonstrate that, although technically demanding, the measurement of protein allergen-induced IgE antibody production in mice using PCA is relatively robust and is transferable and reproducible between laboratories. Once validated, this approach may provide a useful tool for the safety assessment of novel proteins.

    6. Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serum (pages 149–155)

      He Li, Ivan Ricordel, Larry Tong, Lawrence M. Schopfer, Frédéric Baud, Bruno Mégarbane, Eric Maury, Patrick Masson and Oksana Lockridge

      Article first published online: 20 OCT 2008 | DOI: 10.1002/jat.1392

      Blood from humans poisoned with carbofuran was analyzed for the presence of the methylcarbamyl-adduct on serine 198 of butyrylcholinesterase. Multiple reaction monitoring in the QTRAP mass spectrometer identified the modified tryptic peptide of butyrylcholinesterase, thus proving exposure to a carbamate anticholinesterase pesticide.

    7. Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats (pages 156–164)

      Cristina W. Nogueira, Lysandro Pinto Borges and Ana Cristina Guerra Souza

      Article first published online: 6 NOV 2008 | DOI: 10.1002/jat.1394

      Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats.

    8. The role of p44/42 activation in tributyltin-induced inhibition of human natural killer cells: effects of MEK inhibitors (pages 165–173)

      Abraham B. Abraha and Margaret M. Whalen

      Article first published online: 6 NOV 2008 | DOI: 10.1002/jat.1397

      These studies evaluated the role of mitogen activated protein kinase (p44/42) activation in the lytic function of resting human natural killer (NK) cells, as well as in the loss of lytic function that is seen when NK cells are exposed to the environmental contaminant Tributyltin (TBT). The MEK inhibitors, PD98059 and U0126 were used to block activation of P44/42. MEK inhibitors decreased but did not prevent NK lytic function and did not prevent the TBT-induced loss of lytic function.

    9. Effects of the mycotoxin fumonisin B1 on cell death in human kidney cells and human lung fibroblasts in primary culture (pages 174–182)

      G. Schwerdt, M. Königs, H. Holzinger, H. U. Humpf and M. Gekle

      Article first published online: 6 NOV 2008 | DOI: 10.1002/jat.1398

      Cell death and collagen and fibronectin secretion pattern was studied in human lung and kidney cells in primary culture after prolonged exposure to the mycotoxin fumonisin B1 (FB1). Apoptosis was slightly increased in lung cells and decreased in kidney cells. Necrosis was slightly decreased in both cell types after 14 days. Collagen I and III secretion were changed but collagen IV and fibronectin secretion were unchanged. The main risk of prolonged FB1 exposure seems to be altered collagen secretion pattern.

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