Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

July 2009

Volume 29, Issue 5

Pages 367–458

  1. Research Articles

    1. Top of page
    2. Research Articles
    3. Short Communications
    4. Toxicological Updates
    1. The role of ZIP8 down-regulation in cadmium-resistant metallothionein-null cells (pages 367–373)

      Hitomi Fujishiro, Satomi Okugaki, Keisuke Kubota, Tastuo Fujiyama, Hideki Miyataka and Seiichiro Himeno

      Version of Record online: 4 FEB 2009 | DOI: 10.1002/jat.1419

      To solve the mechanism of cellular cadmium uptake, we have established cadmium-resistant cells from metallothionein-null mouse cells, in which cadmium accumulation was suppressed. DNA microarray, real-time PCR, and western blot analyses revealed that the expression of ZIP (Zrt-, Irt-related protein) 8, a zinc transporter, was down-regulated in cadmium-resistant cells. Introduction of ZIP8 shRNA into parental cells markedly reduced cadmium accumulation. These data suggest that down-regulation of ZIP8 plays an important role in the reduced cadmium accumulation in our cadmium-resistant cells.

    2. Improved cell sensitivity and longevity in a rapid impedance-based toxicity sensor (pages 374–380)

      Theresa M. Curtis, Joel Tabb, Lori Romeo, Steven J. Schwager, Mark W. Widder and William H. van der Schalie

      Version of Record online: 6 MAR 2009 | DOI: 10.1002/jat.1421

      A number of toxicity sensors for testing field water using eukaryotic cells have been proposed, but it has been difficult to identify sensors with both appropriate sensitivity to toxicants and the potential for long-term viability. Assessment of bovine pulmonary artery endothelial cell monolayer electrical impedance showed promise in a previous systematic evaluation of toxicity sensor technologies. The goal of the study reported here was to improve toxicant responsiveness and field portability of this cell-based toxicity sensor.

    3. Effect of astragaloside IV on the embryo-fetal development of Sprague–Dawley rats and New Zealand White rabbits (pages 381–385)

      Zhu Jiangbo, Wan Xuying, Zhu Yuping, Ma Xili, Zheng Yiwen and Zhang Tianbao

      Version of Record online: 14 APR 2009 | DOI: 10.1002/jat.1422

      Astragaloside IV, a natural product purified from the Chinese medicinal herb Astragalus membranaceus (Fisch) Bge, is now being developed as a cardioprotective agent for treating cardiovascular diseases. In the present study developmental toxicity of astragaloside IV in Sprague-Dawley rats and New Zealand White rabbits was evaluated by intravenously administering astragaloside IV daily to rats at 0.25, 0.5 and 1.0 mg kg−1 on gestation day 6–15, and to rabbits at 0.5, 1.0, 2.0mg kg−1 daily on gestation day 6–18.

    4. Differential mRNA expression of acetylcholinesterase in the central nervous system of rats with acute and chronic exposure of sarin & physostigmine (pages 386–394)

      Iti Bansal, C. K. Waghmare, T. Anand, A. K. Gupta and B. K. Bhattacharya

      Version of Record online: 12 MAR 2009 | DOI: 10.1002/jat.1424

      A time-course study was carried out to measure the acetylcholinesterase (AChE) gene expression in the brain of female rats exposed to different doses of sarin and physostigmine. Short-term effects were studied with an acute single subcutaneous dose (s.c.) of 80 mg kg−1 (0.5 × LD50) sarin. Cortex and cerebellum showed a significant decline in AChE mRNA expression at 2.5, 24 and 72 h. Biochemical studies showed that plasma butrylcholinesterase (BChE) and brain AChE activities were significantly decreased at 2.5 h, which came back to near control values by 24 h in both cases.

    5. Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum (pages 395–402)

      Athina Zira, Emmanuel Mikros, Konstantina Giannioti, Panagiota Galanopoulou, Apostolos Papalois, Charis Liapi and Stamatios Theocharis

      Version of Record online: 6 MAR 2009 | DOI: 10.1002/jat.1425

      The metabonomic approach has been widely used in toxicology to investigate mechanisms of toxicity. In the present study alterations in the metabolic profiles, monitored by 1H-NMR spectroscopy, on serum samples in acetaminophen (APAP)-induced liver injury in rabbits were examined. Furthermore, the effect of the established antidote N-acetylcysteine (NAC) and the proposed antidotes silybinin (SIL), cimetidine (CIM) and SIL/CIM was also investigated. A single dose of APAP (2 g kg−1 b.w., i.g.) was administered to rabbits and APAP combined with the antidotes SIL, CIM and NAC.

    6. Antiapoptotic effects of dietary antioxidants towards N-nitrosopiperidine and N-nitrosodibutylamine-induced apoptosis in HL-60 and HepG2 cells (pages 403–413)

      Almudena García, Paloma Morales, Nuria Arranz, Ma Eugenia Delgado, Joseph Rafter and Ana I. Haza

      Version of Record online: 19 MAR 2009 | DOI: 10.1002/jat.1426

      The present study show that Vitamin C, Diallyl disulfide (DADS) and Dipropyl disulfide (DPDS) reduced the apoptosis induced by N-Nitrosopiperidine (NPIP) and N-Nitrosodibutylamine (NDBA) in HL-60 and HepG2 cells (around 70% of reduction). The data demonstrated that the decrease of NPIP and NDBA-induced apoptosis by vitamin C and DPDS could be related to the inhibition of ROS production. However, more than one mechanism could be implicated in the protective effect of dietary antioxidants towards N-Nitrosamines-induced apoptosis in both cell lines.

    7. Cyclopamine-induced synophthalmia in sheep: defining a critical window and toxicokinetic evaluation (pages 414–421)

      K. D. Welch, K. E. Panter, S. T. Lee, D. R. Gardner, B. L. Stegelmeier and D. Cook

      Version of Record online: 19 MAR 2009 | DOI: 10.1002/jat.1427

      Cyclopamine, a steroidal alkaloid, from the plant Veratrum californicum is teratogenic, causing a range of differentbirth defects. The critical window for cyclopamine-induced synophthalmia formation has been reported to be gestationalday (GD) 14. The objectives of this study were to better describe cyclopamine-induced craniofacial deformities, to betterdefine the window of susceptibility to synophthalmia formation, and to characterize cyclopamine toxicokinetics in sheep.

    8. Oestrogenic activity of benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) in MCF7 human breast cancer cells in vitro (pages 422–434)

      A. K. Charles and P. D. Darbre

      Version of Record online: 31 MAR 2009 | DOI: 10.1002/jat.1429

      Benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) are added to a wide range of bodycare cosmetics used around the human breast. We report here that they all possess partial oestrogen agonist activity in assays using the oestrogen-responsive MCF7 human breast cancer cell line in vitro. Further research is now needed to investigate whether oestrogenic responses are detectable using in vivo models and the extent to which these compounds might be absorbed through human skin and might enter human breast tissues.

    9. Effect of salicylic acid and diclofenac on the medium-chain and long-chain acyl-CoA formation in the liver and brain of mouse (pages 435–445)

      Fumiyo Kasuya, Maya Kazumi, Takao Tatsuki and Risa Suzuki

      Version of Record online: 23 APR 2009 | DOI: 10.1002/jat.1431

      Medium-chain and long-chain acyl-CoA esters are key metabolites in fatty acid metabolism. Effects of salicylic acid on the in vivo formation of acyl-CoAs in mouse liver and brain were investigated. Further, inhibition of the medium-chain and long-chain acyl-CoA synthetases by salicylic acid and diclofenac was determined in mouse liver and brain mitochondria. Acyl-CoA esters were analyzed by liquid chromatography–tandem mass spectrometry. Salicylic acid and diclofenac exhibited the different mechanisms of inhibition of fatty acid metabolism depending on the length of the acyl chain and tissues.

  2. Short Communications

    1. Top of page
    2. Research Articles
    3. Short Communications
    4. Toxicological Updates
    1. Increased expression of the testicular estrogen receptor alpha in adult mice exposed to low doses of methiocarb (pages 446–451)

      Jiyou Han, Mira Park, Jae-Hong Kim, Ahyoung Kim, Miae Won, Dong Ryul Lee, Jeong-Jae Ko, Ho Yoon, Se-Hoon Sim, Kangseok Lee and Jeehyeon Bae

      Version of Record online: 10 FEB 2009 | DOI: 10.1002/jat.1417

      Methiocarb is a widely used carbamate pesticide and a suspected endocrine disrupter. The objective of this study was to examine the in vivo effects of methiocarb at low doses on testicular expression of steroid receptors, spermatogenesis, and sperm quality in adult mice. Eighteen-week-old DBA/2 males were treated with daily intraperitoneal injection of methiocarb (0, 0.03, 0.3, 1.0, or 3.0 µg kg−1 of body weight) for 20 days.

  3. Toxicological Updates

    1. Top of page
    2. Research Articles
    3. Short Communications
    4. Toxicological Updates
    1. Influence of lead acetate on glutathione and its related enzymes in different regions of rat brain (pages 452–458)

      Kiran Kumar Bokara, Iesha Blaylock, Stacy Brown Denise, Rajanna Bettaiya, Sharada Rajanna and Prabhakara Rao Yallapragada

      Version of Record online: 4 MAR 2009 | DOI: 10.1002/jat.1423

      This study is intended to determine the effect of lead acetate on glutathione and its associated enzymes of rat brain. Wistar male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks and parallel controls were maintained. They were sacrificed at the first, fourth and eighth week to isolate whole brains, which were separated into cerebellum, hippocampus, frontal cortex and brain stem. The data indicate enhanced (P < 0.05) glutathione peroxidise (G-Px) activity at most of the intervals for cerebellum, frontal cortex and brain stem, suggesting conversion of GSH to GSSG, while the hippocampus showed decreased levels.

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