Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

January 2013

Volume 33, Issue 1

Pages 1–77

  1. Review Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Dioxins: diagnostic and prognostic challenges arising from complex mechanisms (pages 1–8)

      Noel M. Rysavy, Kristina Maaetoft-Udsen and Helen Turner

      Version of Record online: 18 MAY 2012 | DOI: 10.1002/jat.2759

      Dioxins are ubiquitous environmental challenges to humans, with a pervasiveness that arises from 200 years of rapid industrialization. Despite their penetrance of the human biota, these compounds are poorly understood in terms of their true physiological potential for harm, and the mechanisms by which they impact cellular and organ level function are only recently becoming clear. Here, we summarize dioxin exposure paradigms and the resulting physiological effects that have been documented in animals and humans.

    2. A review of the most economically important poisonous plants to the livestock industry on temperate grasslands of China (pages 9–17)

      Mengli Zhao, Xinlei Gao, Jing Wang, Xiaolei He and Bing Han

      Version of Record online: 27 SEP 2012 | DOI: 10.1002/jat.2789

      A review of the Chinese literature was conducted to summarize the occurrence of poisonous plant species on temperate grasslands in China. We focus on locoweeds (Astragalus and Oxytropis spp.), drunken horse grass (Achnatherum inebrians [Hance] Keng ex Tzvelev), and langdu (Stellera chamaejasme L.) for information on their toxins, distribution and ecology, control methods and alternate uses. Of the almost 1300 poisonous species found on grasslands in China, these species are responsible for an estimated 80% of all livestock losses.

  2. Research Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Pharmacokinetic study of two acetylcholinesterase reactivators, trimedoxime and newly synthesized oxime K027, in rat plasma (pages 18–23)

      Jana Zdarova Karasova, Jaroslav Chladek, Milos Hroch, Fusek Josef, Daniela Hnidkova and Kamil Kuca

      Version of Record online: 30 JUN 2011 | DOI: 10.1002/jat.1699

      K027 is a promising new acetylcholinesterase reactivator with low acute toxicity and broad spectrum efficacy. The main aim was to compare the pharmacokinetics of K027 and trimedoxime (single i.m. application, equimolar doses). Near identical plasma profiles were obtained for both compounds. No differences were found in the Cmax mean ± SD values and AUC0-180min. However, the percent coefficient of variation of the first-order rate constant of absorption (ka) was 3-fold higher (p<0.01) providing evidence for more erratic absorption of trimedoxime.

    2. Endocrine and testicular changes induced by olanzapine in adult Wistar rats (pages 24–31)

      Simone de Siqueira Bringel, Adelmar Afonso de Amorim Júnior, Marleyne José Afonso Accioly Lins Amorim, Lorena Tavares Brito, Rosana Nogueira Morais, Sandra Maria de Torres, Bruno Mendes Tenorio and Valdemiro Amaro da Silva Junior

      Version of Record online: 21 JUL 2011 | DOI: 10.1002/jat.1702

      Olanzapine is an atypical antipsychotic drug that has been increasingly used in acute treatment and therapeutic support for schizophrenia. Olanzapine treatment induced a reduction in plasma testosterone levels, and testicular, epididymal and prostatic weights. Histopathologic and histomorphometric analysis of spermatogenesis indicated testicular degeneration. Olanzapine treatment in rats promoted endocrinological changes and lesions in the testis, leading to a disturbance in spermatogenesis.

    3. Exposure to the JNK inhibitor SP600125 (anthrapyrazolone) during early zebrafish development results in morphological defects (pages 32–40)

      Eric G. Valesio, Honghong Zhang and Chunbo Zhang

      Version of Record online: 13 JUL 2011 | DOI: 10.1002/jat.1708

      We examined the effects of SP600125 on zebrafish development. It was observed that SP600125 at concentrations equivalent to or lower than its effective dosage as a JNK inhibitor caused severe developmental defects during zebrafish organogenesis. The first noticeable deformities were swim bladder deflation and pericardium edema. Phenotypes of major developmental abnormalities resembled those caused by TCDD, a persistent and dangerous environmental toxin. Our study indicates that SP600125 is unsuitable for zebrafish developmental studies as a JNK inhibitor.

    4. Cloning, expression and functional characterization of carp, Cyprinus carpio, estrogen receptors and their differential activations by estrogens (pages 41–49)

      Yoshinao Katsu, Anke Lange, Shinichi Miyagawa, Hiroshi Urushitani, Norishisa Tatarazako, Yukio Kawashima, Charles R. Tyler and Taisen Iguchi

      Version of Record online: 1 JUL 2011 | DOI: 10.1002/jat.1707

      Environmental estrogens can influence the reproductive system and have been shown to disrupt gametogenesis in males. We cloned all three carp Cyprinus carpio, estrogen receptors [ER; ERa, ERb1 and ERb2] and applied a transient transfection ERE-luciferase reporter assay system using mammalian cells. cERb2 showed a higher sensitivity to the natural steroid oestrogen, 17b-estradiol, than cERa. This is a powerful assay for toxicology, and provides a tool for future studies examining the receptor-environmental chemical interactions and estrogen disrupting mechanisms in carp.

    5. Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD50 yields insight into the efficacy of prophylactics (pages 50–55)

      Mandy L. Marziaz, Kathryn Frazier, Paul B. Guidry, Robyn A. Ruiz, Ilona Petrikovics and Donovan C. Haines

      Version of Record online: 13 JUL 2011 | DOI: 10.1002/jat.1709

      Cytochrome c oxidase activity in brains excised from mice treated with cyanide and various prophylactic treatments suggests that a recently proposed sulfur donor, thiotaurine, is not as effective as thiosulfate. Further, thiotaurine appeared to inhibit cytochrome c oxidase activity slightly, independent of cyanide treatment. The EC75 for cytochrome c inhibition by cyanide in the different treatment regimens correlated very well with the LD50 determined from mortality data, supporting cytochrome c oxidase inhibition as a major mechanism for cyanide toxicity.

    6. An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations (pages 56–62)

      Domagoj Dinter, Goran Gajski and Vera Garaj-Vrhovac

      Version of Record online: 7 JUL 2011 | DOI: 10.1002/jat.1711

      The present study evaluated the cytogenotoxic potential of antimalarial drug atovaquone towards human lymphocytes. Two different clinically relevant concentrations of atovaquone obtained from the plasma concentrations used for prophylactic treatment and the treatment of malaria were used with and without S9 metabolic activation. Atovaquone was not cytogenotoxic in the given concentrations, regardless of metabolic activation. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity.

    7. Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (pages 63–70)

      Dojung Kim, Young-Joo Lee, Heui-Young Ryu, Jin-Hee Lee, Hyun-Kyung Kim, Eunhee Kim, Jae-Dong Moon, Dong Deuk Chang and Hae-Seong Yoon

      Version of Record online: 1 DEC 2011 | DOI: 10.1002/jat.1712

      Heterocyclic amines (HCAs) are naturally produced during cooking processes for meats and fish. Among HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as ‘reasonably anticipated to be a human carcinogen’. The present study investigated the correlation between human exposure levels of PhIP and the role of genetic polymorphisms of enzymes on PhIP metabolism. The SNPs of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P< 0.05). These results could improve understanding of populations subject to PhIP-derived health risk.

    8. Ethyl pyruvate protects rats from phosgene-induced pulmonary edema by inhibiting cyclooxygenase2 and inducible nitric oxide synthase expression (pages 71–77)

      Hong-li Chen, Hua Bai, Miao-miao Xi, Riu Liu, Xu-jun Qin, Xin Liang, Wei Zhang, Xiao-di Zhang, Wen-li Li and Chun-xu Hai

      Version of Record online: 5 AUG 2011 | DOI: 10.1002/jat.1713

      Phosgene can induce fatal pulmonary edema. Oxidative stress and inflammatory responses are believed to be involved in this process. In the present study, we aim to investigate the therapeutic effects of ethyl pyruvate (EP) on phosgene-induced pulmonary edema and the underlying mechanisms. We found that EP had a protective role against phosgene-induced pulmonary edema, which was mediated in part by inhibiting MAPK activation and subsequently down-regulating COX-2 and iNOS expression as well as decreasing the production of NO and PGE2.