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  • The protective effect of thymoquinone on tert-butylhydroquinone induced cytotoxicity in human umbilical vein endothelial cells†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-29
    Zahra Karimi, Maryam Ghaffari, Jafar Ezzati Nazhad Dolatabadi, Parvin Dehghan
    更新日期:2019-12-09
  • 更新日期:2019-12-09
  • Benzoquinone alters the lipid homeostasis in Saccharomyces cerevisiae†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-20
    Abhishek Raj, Vasanthi Nachiappan
    更新日期:2019-12-09
  • Phytochemicals protect L02 cells against hepatotoxicity induced by emodin via the Nrf2 signaling pathway†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-20
    Yan Yan, Kang Wang, Xu Tang, Jun-feng Gao, Bin-yu Wen
    更新日期:2019-12-09
  • Application of the direct peptide reactivity assay (DPRA) to inorganic compounds: a case study of platinum species†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-20
    Jocelyn D. C. Hemming, Mark Hosford, Martin M. Shafer
    更新日期:2019-12-09
  • Nanoparticle induced barrier function assessment at liquid–liquid and air–liquid interface in novel human lung epithelia cell lines†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-19
    Lars Leibrock, Sandra Wagener, Ajay Vikram Singh, Peter Laux, Andreas Luch
    更新日期:2019-12-09
  • Astaxanthin reduces perfluorooctanoic acid cytotoxicity in Saccharomyces cerevisiae
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-18
    S. J. Sudharshan, Raghavendra Tirupathi, Madhu Dyavaiah
    更新日期:2019-12-09
  • Astilbin attenuates cerebral ischemia/reperfusion injury by inhibiting the TLR4/MyD88/NF-κB pathway
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-18
    Jing Li, Zhaowei Gu, Yue Liu, Yu Wang, Min Zhao
    更新日期:2019-12-09
  • Methanol extract of Iphiona aucheri ameliorates CCl4 induced hepatic injuries by regulation of genes in rats†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-11-14
    Jawaid Ahmed Zai, Muhammad Rashid Khan, Zaib un Nisa Mughal, Riffat Batool, Irum Naz, Sonia Maryam, Zartash Zahra
    更新日期:2019-12-09
  • 更新日期:2019-12-09
  • 更新日期:2019-12-09
  • Cigarette smoke inhalation aggravates diabetic kidney injury in rats†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-29
    Songling Jiang, Do Van Quan, Jae Hyuck Sung, Moo-Yeol Lee, Hunjoo Ha
    更新日期:2019-12-09
  • Novel evaluation of sevoflurane anesthetic exposure on the testicular germ cells of neonatal male mice
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-24
    Ali Raza Ebrahim Soltani, Abdolmohammad Kajbafzadeh, Maryam Ezzati, Zahra Ebrahim Soltani, Navid Hosseinifar, Anahid Maleki, Maryam Nezhad Sistani
    更新日期:2019-12-09
  • Innovative models for in vitro detection of seizure
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-24
    Kimberly L. Rockley, Ruth A. Roberts, Michael J. Morton
    更新日期:2019-12-09
  • 更新日期:2019-12-09
  • Cadmium telluride quantum dot-exposed human bronchial epithelial cells: a further study of the cellular response by proteomics†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-22
    Yan-Ming Xu, Heng Wee Tan, Wei Zheng, Zhan-Ling Liang, Fei-Yuan Yu, Dan-Dan Wu, Yue Yao, Qiu-Hua Zhong, Rui Yan, Andy T. Y. Lau
    更新日期:2019-12-09
  • Biogenic Aspergillus tubingensis silver nanoparticles’ in vitro effects on human umbilical vein endothelial cells, normal human fibroblasts, HEPG2, and Galleria mellonella
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-10
    Cristiane Angélica Ottoni, Durvanei Augusto Maria, Priscila Jane Romano de Oliveira Gonçalves, Welington Luiz de Araújo, Ana Olívia de Souza
    更新日期:2019-12-09
  • Reply to the ‘Comment on “Acetylcysteine in paracetamol poisoning: a perspective of 45 years of use”’ by M. E. Mullins, M. C. Yarema, M. L. A. Sivilotti, M. Thompson, D. A. Algren, M. C. Beuhler and C. P. Holstege, Toxicol. Res., 2019, 8, DOI: 10.1039/C9TX00158A
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-03
    D. Nicholas Bateman, James W. Dear

    Mullins et al. made a comment on our article (DOI: 10.1039/C9TX00002J) stating they noticed the omission of the one-bag, standard concentration protocol which is shared by several centers in North America when we discussed IV acetylcysteine protocols. In this reply we clarify that we did not include this methodology as it is a technical adaption of the way in which a 2-bag NAC regimen in administered and there is insufficient comparative data with other regimens.

    更新日期:2019-12-09
  • Environmental distribution of the neurotoxin l-BMAA in Paenibacillus species
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-03
    Peter B. Nunn, Geoffrey A. Codd
    更新日期:2019-12-09
  • Thyroid endocrine status and biochemical stress responses in adult male Wistar rats chronically exposed to pristine polystyrene nanoplastics†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-10-02
    Fatemeh Amereh, Akbar Eslami, Simin Fazelipour, Mohammad Rafiee, Mohammad Ismail Zibaii, Mohammad Babaei
    更新日期:2019-12-09
  • Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress
    Toxicol. Res. (IF 1.593) Pub Date : 2019-09-27
    Li Pang, Ping Deng, Yi-dan Liang, Jing-yu Qian, Li-Chuan Wu, Ling-ling Yang, Zheng-ping Yu, Zhou Zhou
    更新日期:2019-12-09
  • 更新日期:2019-12-09
  • Ex vivo toxicological evaluation of experimental anticancer gold(i) complexes with lansoprazole-type ligands†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-09-20
    Natalia Estrada-Ortiz, Elena Lopez-Gonzales, Ben Woods, Stefan Stürup, Inge A. M. de Graaf, Geny M. M. Groothuis, Angela Casini
    更新日期:2019-12-09
  • Characteristic synergistic cytotoxic effects toward cells in graphene oxide dressing with cadmium and copper ions
    Toxicol. Res. (IF 1.593) Pub Date : 2019-09-16
    Yiyang Dong, Yulin Chang, Haidi Gao, Victoria Arantza León Anchustegui, Qiang Yu, Haifang Wang, Jia-Hui Liu, Shihui Wang
    更新日期:2019-12-09
  • Comment on “Acetylcysteine in paracetamol poisoning: a perspective of 45 years of use” by D. N. Bateman and J. W. Dear, Toxicol. Res., 2019, 8, 489
    Toxicol. Res. (IF 1.593) Pub Date : 2019-09-11
    Michael E. Mullins, Mark C. Yarema, Marco L. A. Sivilotti, Margaret Thompson, D. Adam Algren, Michael C. Beuhler, Christopher P. Holstege

    We point out an acetylcysteine protocol that a previous article (D. N. Bateman and J. W. Dear, Toxicol. Res., 2019, 8, 489–498) overlooked. The standard concentration protocol uses a uniform concentration of 30 mg mL−1 for all patients to reduce errors in preparation and administration. Usually a single 1 L bag is sufficient for most patients. Various centers in the US and Canada use this approach.

    更新日期:2019-12-09
  • Kaempferol derivatives isolated from Lens culinaris Medik. reduce DNA damage induced by etoposide in peripheral blood mononuclear cells
    Toxicol. Res. (IF 1.593) Pub Date : 2019-09-10
    Magdalena Kluska, Michał Juszczak, Daniel Wysokiński, Jerzy Żuchowski, Anna Stochmal, Katarzyna Woźniak
    更新日期:2019-12-09
  • miR-140-5p mediates bevacizumab-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway
    Toxicol. Res. (IF 1.593) Pub Date : 2019-09-05
    Xuan-Ying Chen, Wei-Lin Huang, Xiao-Ping Peng, Yan-Ni Lv, Jun-He Li, Jian-Ping Xiong
    更新日期:2019-12-09
  • Tin thiocarbonohydrazone complexes: synthesis, crystal structures and biological evaluation†
    Toxicol. Res. (IF 1.593) Pub Date : 2019-08-30
    Jin Wang, Yu-Ting Wang, Yan Fang, Yan-Li Lu, Ming-Xue Li
    更新日期:2019-12-09
  • Eco-friendly synthesis of glutathione-capped CdTe/CdSe/ZnSe core/double shell quantum dots: their cytotoxicity and genotoxicity effects on Chinese hamster ovary cells
    Toxicol. Res. (IF 1.593) Pub Date : 2019-08-26
    Neo Mervyn Monaheng, Sundararajan Parani, Mary Gulumian, Oluwatobi Samuel Oluwafemi
    更新日期:2019-12-09
  • Integrated network pharmacology and targeted metabolomics to reveal the mechanism of nephrotoxicity of triptolide
    Toxicol. Res. (IF 1.593) Pub Date : 2019-08-07
    Wei Huang, Chuanxin Liu, Lijuan Xie, Yuming Wang, Yanyan Xu, Yubo Li
    更新日期:2019-12-09
  • Prometryn induces apoptotic cell death through cell cycle arrest and oxidative DNA damage
    Toxicol. Res. (IF 1.593) Pub Date : 2019-07-26
    Qiaoyun Liu, Longsheng Wang, Hanwen Chen, Bo Huang, Jiawei Xu, Ying Li, Paul Héroux, Xinqiang Zhu, Yihua Wu, Dajing Xia
    更新日期:2019-12-09
  • Serum miRNAs are differentially altered by ethanol and caffeine consumption in rats
    Toxicol. Res. (IF 1.593) Pub Date : 2019-07-17
    M. Martinez, I. M. U. Rossetto, R. M. S. Arantes, F. S. N. Lizarte, L. F. Tirapelli, D. P. C. Tirapelli, L. G. A. Chuffa, F. E. Martinez
    更新日期:2019-12-09
  • MicroRNA-338-5p modulates pulmonary hypertension-like injuries caused by SO2, NO2 and PM2.5 co-exposure through targeting the HIF-1α/Fhl-1 pathway.
    Toxicol. Res. (IF 1.593) Pub Date : 2016-09-09
    Xiaotong Ji,Yingying Zhang,Tingting Ku,Yang Yun,Guangke Li,Nan Sang

    The role of ambient air pollution is considered to be important in the development of chronic obstructive pulmonary disease (COPD), and pulmonary hypertension (PH) is a common clinical manifestation of COPD. However, many studies have mainly focused on the adverse health effects of a single air pollutant, ignoring the combined toxicity of multiple pollutants. In the present study, we co-exposed mice to coal-burning air pollutants (SO2, NO2 and PM2.5), and confirmed PH-like injury occurrence by airflow limitation, marked abnormal endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) expression, and histopathological and ultrastructural alteration. Global microRNA (miRNA) arrays identified three significantly changed miRNAs homologous with humans (miR-338-5p, miR-450b-3p and miR-142-5p), and we targeted miR-338-5p based on real-time reverse transcription-PCR (RT-PCR) validation. Furthermore, bioinformatic and dual-luciferase reporter gene analyses indicated that miR-338-5p bound to 3'-UTR of hypoxia-inducible factor 1α (HIF-1α) mRNA and down-regulation of miR-338-5p led to the increased expression of HIF-1α and its related gene four-and-a-half LIM (Lin-11, Isl-1 and Mec-3) domain 1 (Fhl-1) and contributed to PH. This study provides evidence for the role of miRNAs in PH through targeting HIF-1α/Fhl-1 pathway after air pollutants co-exposure and implies new insights into the molecular markers for COPD caused by air pollution.

    更新日期:2019-11-01
  • Correction: In vitro toxicity evaluation of silica-coated iron oxide nanoparticles in human SHSY5Y neuronal cells.
    Toxicol. Res. (IF 1.593) Pub Date : 2016-05-05
    Gözde Kiliç,Carla Costa,Natalia Fernández-Bertólez,Eduardo Pásaro,João Paulo Teixeira,Blanca Laffon,Vanessa Valdiglesias

    [This corrects the article DOI: 10.1039/c5tx00206k.].

    更新日期:2019-11-01
  • Correction: A possible new mechanism and drug intervention for kidney damage due to arsenic poisoning in rats.
    Toxicol. Res. (IF 1.593) Pub Date : 2016-02-24
    Yu-Yan Xu,Qi-Bing Zeng,Mao-Lin Yao,Chun Yu,Jun Li,Ai-Hua Zhang

    [This corrects the article DOI: 10.1039/C5TX00165J.].

    更新日期:2019-11-01
  • A comparative study of hydrophilic phosphine hexanuclear rhenium cluster complexes' toxicity.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-05-17
    Anna A Krasilnikova,Anastasiya O Solovieva,Anton A Ivanov,Konstantin A Brylev,Tatiana N Pozmogova,Marina A Gulyaeva,Olga G Kurskaya,Alexander Y Alekseev,Alexander M Shestopalov,Lidiya V Shestopalova,Alexander F Poveshchenko,Olga A Efremova,Yuri V Mironov,Michael A Shestopalov

    The octahedral rhenium cluster compound Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] has recently emerged as a very promising X-ray contrast agent for biomedical applications. However, the synthesis of this compound is rather challenging due to the difficulty in controlling the hydrolysis of the initial P(C2H4CN)3 ligand during the reaction process. Therefore, in this report we compare the in vitro and in vivo toxicity of Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] with those of related compounds featuring the fully hydrolysed form of the phosphine ligand, namely Na2H14[{Re6Q8}(P(C2H4COO)3)6] (Q = S or Se). Our results demonstrate that the cytotoxicity and acute in vivo toxicity of the complex Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] solutions were considerably lower than those of compounds with the fully hydrolysed ligand P(C2H4COOH)3. Such behavior can be explained by the higher osmolality of Na2H14[{Re6Q8}(P(C2H4COO)3)6] versus Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6].

    更新日期:2019-11-01
  • A comparison of toxicity and toxicokinetics in rats and dogs following twenty-eight-day, repeat-dose oral administration of nifurtimox.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-05-17
    Ye Li,Tian-Tian Liu,Hong-Tao Jin,Piao-Piao Zhang,Dan Qin,Qian-Qian Zhang,Wen-Tao Wu,Cui-Ping Yang,Ai-Ping Wang

    Nifurtimox has been an important treatment for trypanosomiasis for many years, but new research indicates that the drug may also be an effective therapy for malignant neuroblastoma. However, there have been few published reports evaluating the toxicity of nifurtimox in different species. Therefore, to further understand its toxicity and toxicokinetic profiles, Sprague Dawley rats and beagle dogs were orally administered nifurtimox at 0, 25, 75 and 150 mg kg-1 day-1, and 0, 30, 60 and 120 mg kg-1 day-1, respectively, for 28 days, which was followed by a 28-day recovery period. Significant decreases in the body weight and food consumption were observed in rats given 75 and 150 mg kg-1 day-1, but no significant difference was observed in either body weight or food consumption in dogs. No notable gender difference was observed in the rats in our study. The mean Cmax and AUC0-t increased with the exposure time in rats, and systemic exposure on day 28 was notably higher than that on day 1 for each dosing group. In contrast, in dogs the mean Cmax and AUC0-t increased significantly in the 120 mg kg-1 day-1 group only. Other findings in rats included a dose-dependent increase in total bilirubin and urea, a significant increase in the kidney organ coefficient, a decrease in heart and thymus weights, and a decrease in the weight of testes and epididymides tissue in males administered 75 and 150 mg kg-1 day-1, with dead sperms observed in the epididymides and a loss of necrotic cells. Furthermore, the brains of rats administered 150 mg kg-1 day-1 nifurtimox revealed cerebral tissue softening. In dogs there were no treatment-related changes in organ weights during the dosing period. However, deciduous spermatoblasts were observed in the seminiferous tubules and there was a lack of long sperms in the epididymides. The findings from this study demonstrate inter-species differences in nifurtimox toxicity and toxicokinetics. These results are relevant to the evaluation of the wider clinical applications of this drug.

    更新日期:2019-11-01
  • Toxicological effects of graphene oxide on Saccharomyces cerevisiae.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-05-26
    Song Zhu,Fei Luo,Bin Zhu,Gao-Xue Wang

    Using Saccharomyces cerevisiae as an experimental model, the potential toxicity of graphene oxide (GO) was evaluated following exposure to 0-600 mg L-1 for 24 h. The results showed that cell proliferation was observably inhibited and the IC50 value was 352.704 mg L-1. Mortality showed a concentration-dependent increase, and was 19.3% at 600 mg L-1. A small number of cells were deformed and shrunken after exposure. The percentage of late apoptosis/necrosis showed a significant increase (p < 0.01) at 600 mg L-1 (19.16%) compared with the control (1.14%). The mitochondrial transmembrane potential was significantly decreased (p < 0.01) at 50-600 mg L-1, indicating that the apoptosis was related to mitochondrial impairment. Moreover, ROS was observably increased (p < 0.01) at 200, 400 and 600 mg L-1. The expressions of apoptosis-related genes (SOD, Yca1, Nma111 and Nuc1) were significantly changed. The results presented so far indicate that GO has the potential to cause adverse effects on organisms when released into the environment.

    更新日期:2019-11-01
  • Eugenia uniflora leaf essential oil promotes mitochondrial dysfunction in Drosophila melanogaster through the inhibition of oxidative phosphorylation.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-05-05
    Nélson R de Carvalho,Nathane R Rodrigues,Giulianna E Macedo,Ivi J Bristot,Aline A Boligon,Marli M de Campos,Francisco A B Cunha,Henrique D Coutinho,Fabio Klamt,Thomas J S Merritt,Thaís Posser,Jeferson L Franco

    Eugenia uniflora L. (Myrtaceae family) has demonstrated several properties of human interest, including insecticide potential, due to its pro-oxidant properties. These properties likely result from the effects on its mitochondria, but the mechanism of this action is unclear. The aim of this work was to evaluate the mitochondrial bioenergetics function in Drosophila melanogaster exposed to E. uniflora leaf essential oil. For this, we used a high-resolution respirometry (HRR) protocol. We found that E. uniflora promoted a collapse of the mitochondrial transmembrane potential (ΔΨm). In addition the essential oil was able to promote the disruption of respiration coupled to oxidative phosphorylation (OXPHOS) and inhibit the respiratory electron transfer system (ETS) established with an uncoupler. In addition, exposure led to decreases of respiratory control ratio (RCR), bioenergetics capacity and OXPHOS coupling efficiency, and induced changes in the substrate control ratio. Altogether, our results suggested that E. uniflora impairs the mitochondrial function/viability and promotes the uncoupling of OXPHOS, which appears to play an important role in the cellular bioenergetics failure induced by essential oil in D. melanogaster.

    更新日期:2019-11-01
  • Potential effects of low molecular weight phthalate esters (C16H22O4 and C12H14O4) on the freshwater fish Cyprinus carpio.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-26
    R K Poopal,M Ramesh,V Maruthappan,R Babu Rajendran

    The aim of the present study is to assess the toxic effect of dibutyl phthalate (DBP) and diethyl phthalate (DEP) on the freshwater fish Cyprinus carpio. The median lethal concentrations of DBP and DEP for 96 h are found to be 35 and 53 mg L-1, respectively. Fish were exposed to 3.5 mg L-1 (Treatment I) and 1.75 mg L-1 (Treatment II) of DBP and 5.3 mg L-1 (Treatment I) and 2.65 mg L-1 (Treatment II) of DEP for a period of 35 days. The DBP and DEP exposed fish show a concentration based toxic effect on the selected parameters of this study. The hematological parameters, such as hemoglobin (Hb), hematocrit (Hct) and erythrocyte (RBC), were found to decrease in the DBP and DEP treated fish, whereas their leucocyte (WBC) count increased compared to that of the control groups. A biphasic response is noted in the erythrocyte indices, such as mean cellular volume (MCV), mean cellular hemoglobin (MCH) and mean cellular hemoglobin concentration (MCHC), throughout the study period. Exposure to DBP and DEP caused a significant (p < 0.05) decrease in sodium (Na+), potassium (K+), and chloride (Cl-) levels in the gill and brain of the fish throughout the study period when compared to that of their respective controls. The plasma protein level decreased in all the treatments, whereas the plasma glucose level significantly increased in the DBP and DEP exposed fish. Maximum inhibition of Na+/K+-ATPase activity was noticed in the gill and brain of the fish exposed to DBP and DEP. The cholinesterase (ChE) activity in the brain of the fish significantly decreased throughout the study period. A significant (p < 0.05) increase in glutamate oxaloacetate transaminase (GOT) and glutamic pyruvate transaminase (GPT) activity was noted in the fish exposed to both toxicants. The antioxidant enzymatic parameters such as superoxide dismutase (SOD) and catalase (CAT) activities were found to decrease in the gill and liver of the DBP and DEP treated fish, whereas a significant (p < 0.05) increase in lipid peroxidation (LPO) was observed. The above mentioned parameters could be used as potential biomarkers in clinical trials for the assessment of plasticizers. This study provides indispensable information towards future research on the effect of plasticizers on non-target organisms including humans.

    更新日期:2019-11-01
  • Protective effects of coenzyme Q10 and resveratrol on oxidative stress induced by various dioxins on transheterozigot larvae of Drosophila melanogaster.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-05-08
    Deniz Altun Çolak,Handan Uysal

    Dioxin and dioxin-like compounds are known as a class of highly toxic and persistent environmental contaminants threatening human and animal health. In the present study, the protective effects of Coenzyme Q10 (CoQ10) and Resveratrol (RSV) against 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,7,8,9-HxCDD, and 1,2,3,4,6,7,8,9-OCDD induced acute toxicity and measurement of oxidative stress were studied. Lethal doses of these chemicals were determined. Transheterozigot larvae of Drosophila melanogaster were treated using either dioxins (10 × 10-7 μg mL-1) or dioxins + CoQ10 (10 × 10-7 μg mL-1 + 150 μg mL-1) and dioxins + RSV (10 × 10-7 μg mL-1 + 100 μM). After dioxin treatment, antioxidant combination therapy with dioxins and CoQ10 or dioxins and RSV resulted in indicators of acute toxicity including a decrease in total oxidant status as compared to dioxins alone (p < 0.05). The combination treatment also produced a significant increase in total antioxidant status as compared to dioxins only (p < 0.05). Results indicate a potential role of dioxins for oxidative stress with acute toxicity and the protective performance of CoQ10 and RSV in the overall toxicity of dioxins including measuring oxidative stress.

    更新日期:2019-11-01
  • Zinc is a determinant of the cytotoxicity of Ziram, a dithiocarbamate fungicide, in rat thymic lymphocytes: possible environmental risks.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-18
    Yumiko Kanemoto-Kataoka,Tomohiro M Oyama,Hitoshi Ishibashi,Yasuo Oyama

    Ziram, one of the dithiocarbamate fungicides, is widely applied to agriculture because this agent protects various crops from fungal infections. Risks of dithiocarbamate biocide use are of concern. It was previously reported that Ziram increased the intracellular concentration of Zn2+. Therefore, we cytometrically studied the mechanism of Zn2+-dependent lethal actions of Ziram on rat lymphocytes at environmentally relevant Zn2+ levels. Membrane and cellular parameters of rat lymphocytes were estimated by flow-cytometric techniques with appropriate fluorescent probes. The Ziram-induced increase in cell lethality was completely attenuated by Zn2+ chelators. A significant increase of cell lethality was found on the simultaneous application of Ziram at a sublethal concentration and ZnCl2. The combination of Ziram and ZnCl2 increased the cellular superoxide anion content and decreased the cellular GSH content, which possibly caused the increase in cell lethality. The zinc concentrations under the present experimental conditions were comparable to the environmentally relevant concentrations found in rivers. Therefore, the environmental level of zinc may be critical in estimating the toxicity of Ziram to wild animals.

    更新日期:2019-11-01
  • Biosafety study and mechanism comparison on two types of silica with different nanostructures.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-24
    Yang Zhang,Xianhui Chen,Bo Zhao,Hounan Wu,Lan Yuan,Hua Zhang,Wenbing Dai,Bing He,Gengmei Xing,Qiang Zhang,Xueqing Wang

    Silica is frequently used in oral drug delivery; however, its biosafety, particularly concerned with its nanostructure, has not been comprehensively studied yet. Here, the in vitro and in vivo biosafety of two types of silica (A200, nano-sized or micron-sized agglomerates; S350, micro-sized particles with nanopores) were compared and the possible reasons for the differences were explored. The results indicated that both A200 and S350 could inhibit the growth of Caco-2 cells by inducing apoptosis and changing the cell cycle progression. A200 showed a stronger influence than S350 in most of the in vitro experiments. In the in vivo study in KM mice, both A200 and S350 could change the blood constituents under the tested conditions; A200 also increased the levels of inflammatory factors in plasma and the numbers of CD4+ lymphocyte subsets. No obvious organic damage was observed in either the A200-treated or S350-treated groups. The transport study showed that neither A200 nor S350 were readily transported across the intestinal epithelial barrier in vitro and in vivo, but A200 could transport across the lymphatic-associated epithelium and accumulate in the Peyer's Patches, which might explain the A200-induced immune response. The increased transport of A200 might relate to its particle size, dispersion state and specific surface area. In conclusion, these results demonstrated that A200 and S350 exhibited diverse biosafety aspects, which correlated with their different nanostructures. We believe this study will provide some scientific information about the biosafety of A200 and S350 for their applications in oral drug delivery systems.

    更新日期:2019-11-01
  • Differential gene responses in the embryo of the green mussel Perna viridis exposed to dichlorodiphenyltrichloroethane (DDT).
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-18
    Xiu Jiang,Tianle Tang,Hongwei Zhao,Qinqin Song,Hailong Zhou,Qian Han,Xiaoping Diao

    The green-lipped mussel, Perna viridis, is considered to be an ideal indicator for marine environmental pollution. Dichlorodiphenyltrichloroethane (DDT), a typical persistent organic pollutant, is extensively distributed in marine environments. However, little is known about the toxic effects of DDT on the embryo of marine animals, particularly in marine bivalves. Using next-generation sequencing technology, we studied P. viridis embryo after DDT stress at the transcriptome level. A total of 99 202 unigenes were obtained based on the 2383 bp of unigene N50. These differentially expressed genes (DEGs) participated in the various molecular pathways of biological effects, including oxidative stress, detoxification, innate immunity and neurobehavioral disease. Quantitative real-time PCR was performed to verify the mRNA expression of several genes identified by differential gene expression (DGE) analysis. The results indicated that DDT was in induced a dose-dependent manner in the embryo of P. viridis, and most genes involved in oxidative stress and detoxification were up-regulated by DDT exposure; however, the immunity-related genes were down-regulated, except the genes involved in phagocytosis. Gene expression changes in embryo from P. viridis provide a preliminary basis to better understand the molecular toxic response mechanisms of embryo to DDT.

    更新日期:2019-11-01
  • ATF2 partly mediated the expressions of proliferative factors and inhibited pro-inflammatory factors' secretion in arsenite-treated human uroepithelial cells.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-03-29
    Shengnan Liu,Fei Wang,Jieyu Liu,Peiyu Jin,Xiaoyan Wang,Li Yang,Shuhua Xi

    Inorganic arsenic (iAs) could induce the expression of activating transcription factor-2 (ATF2) in the human urinary bladder epithelial cell line (SV-HUC-1 cells). ATF2, as a member of the bZIP transcription factor family, has been implicated in a transcriptional response leading to cell growth, migration and malignant tumor progression. However, little is known about the effects of ATF2 on proliferative factors in iAs treated human urothelial cells. In this study, ATF2 siRNA was employed to investigate the relationship between ATF2 activation and the expressions of proliferative factors, such as BCL2, cyclin D1, COX-2, MMP1 and PCNA, and pro-inflammatory factors (TNFα, TGFα and IL-8) in SV-HUC-1 cells. The results showed that low concentration arsenite increased the expressions of proliferative factors BCL2, cyclin D1, COX-2, MMP1 and PCNA in SV-HUC-1 cells, and ATF2 siRNA partly decreased the expressions of BCL2, cyclin D1, and COX-2. A neutralizing antibody of IL-8 was used for attenuating the levels of IL-8 and neutralizing antibody of IL-8 did not relieve the expressions of ATF2 and proliferative factors induced by arsenite in SV-HUC-1 cells. In addition, ATF2 knockdown did not decrease the expressions of pro-inflammatory cytokines induced by arsenite in SV-HUC-1 cells, but dramatically increased mRNA expressions of TNFα, TGFα and IL-8 under arsenite and non-arsenite conditions. In conclusion, our present study indicated that ATF2, but not IL-8, played a partial role in the expressions of proliferative factors induced by arsenite in human uroepithelial cells.

    更新日期:2019-11-01
  • A developmental toxicity assay of Carpesii Fructus on zebrafish embryos/larvae.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-03-29
    Qing Xia,Jun Luo,Xue Mei,Yutong Wang,Wanzhen Huang,Jinfeng Wang,Ranran Yang,Zhiqiang Ma,Ruichao Lin

    Carpesii Fructus, the dried fruit of Carpesium abrotanoides L., has been used as a traditional Chinese medicine for centuries to kill intestinal parasites in children. It has been recorded as a mildly toxic medicine in the Chinese pharmacopoeia. However, little proof of its toxicology has been reported in modern pharmacology. This study investigated for the first time its developmental toxicity on zebrafish embryos/larvae from 6 to 96 h post-fertilization (hpf). In addition, the enzymes and genes associated with oxidative stress and apoptosis were tested to investigate the potential toxicologic mechanism preliminarily. The observation of toxicologic endpoints showed the developmental toxicity of Carpesii Fructus. Pericardial edema, yolk sac edema, bleeding tendency, and enlarged yolk were the most commonly occurring morphological changes observed in our study. According to the results of acridine orange staining and morphological observation, the developing heart was speculated to be the target organ of toxicity. Furthermore, Carpesii Fructus exposure changed the activities of defense enzymes, increased malondialdehyde (MDA) content, decreased caspase-3 activity, and altered mRNA levels of related genes (ogg1, p53, Cu/Zn-Sod, Mn-Sod, and Cat↓; Gpx↑) in zebrafish larvae, indicating that oxidative stress and additional apoptosis should have roles in the developmental toxicity of Carpesii Fructus. This is the first study that provides proof of modern pharmacology on the teratogenicity and possible toxicologic mechanism of Carpesii Fructus.

    更新日期:2019-11-01
  • Regulating temperature and relative humidity in air-liquid interface in vitro systems eliminates cytotoxicity resulting from control air exposures.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-05-23
    Jose Zavala,Rebecca Greenan,Q Todd Krantz,David M DeMarini,Mark Higuchi,M Ian Gilmour,Paul A White

    VITROCELL® systems permit cell exposures at the air-liquid interface (ALI); however, there are inconsistent methodologies in the literature for their operation. Some studies find that exposure to air (vehicle control) induced cytotoxicity relative to incubator controls; others do not mention if any cytotoxicity was encountered. We sought to test whether temperature and relative humidity (temp/RH) influence cytotoxicity with an unmodified (conditions A & B) and modified (condition C) VITROCELL® 6 CF with temp/RH controls to permit conditioning of the sampled air-flow. We exposed BEAS-2B cells for 1 h to air and measured viability (WST-1 cell proliferation assay) and lactate dehydrogenase (LDH) release 6 h post-exposure. Relative to controls, cells exposed to air at (A) 22 °C and 18% RH had a 47.9% ± 3.2% (p < 0.0001) reduction in cell viability and 10.7% ± 2.0% (p < 0.0001) increase in LDH release (B) 22 °C and 55% RH had a 40.3% ± 5.8% (p < 0.0001) reduction in cell viability and 2.6% ± 2.0% (p = 0.2056) increase in LDH release, or (C) 37 °C and >75% RH showed no changes in cell viability and no increase in LDH release. Furthermore, cells exposed to air at 37 °C and >75% RH 24 h post-exposure showed no changes in viability or LDH release relative to incubator controls. Thus, reductions in cell viability were induced under conditions used typically in the literature (conditions A & B). However, our modifications (condition C) overcome this shortcoming by preventing cell desiccation; regulating temp/RH is essential for conducting adequate ALI exposures.

    更新日期:2019-11-01
  • Mucor circinelloides: efficiency of bioremediation response to heavy metal pollution.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-05-09
    Xu Zhang,Huanhuan Yang,Zhaojie Cui

    Mucor circinelloides, selected from mine tailings for heavy metal bioremediation, was characterized at the genetic level by internal transcribed spacer (ITS) analysis. M. circinelloides was first applied for the absorption of heavy metals {Fe(iii), Mn(ii), Cu(ii), Zn(ii), and Pb(ii)}. The minimal inhibitory concentration test showed that M. circinelloides could tolerate relatively high concentrations of heavy metals. M. circinelloides could uptake 79.5%, 44.1%, 62.5%, 56.5%, and 85.5% of Fe(iii), Mn(ii), Cu(ii), Zn(ii), and Pb(ii), respectively, from the initial concentration of 20 mg L-1 under optimum conditions (pH 8; 30 °C). Monitoring the change in ATPase activity at certain intervals indicated that the mechanism of bioremediation was directly related to the energy consumption. M. circinelloides will be widely used for in-situ remediation in special environment because of strong vitality and excellent bioremediation efficiency.

    更新日期:2019-11-01
  • The muscarinic effect of anhydroecgonine methyl ester, a crack cocaine pyrolysis product, impairs melatonin synthesis in the rat pineal gland.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-03-29
    Lívia Silva Medeiros de Mesquita,Raphael Caio Tamborelli Garcia,Fernanda Gaspar Amaral,Rafael Peres,Simone Miller Wood,RodrigoVincenzo de Luca Lucena,Eduardo Osório Frare,Mariana Vieira Abrahão,Tania Marcourakis,José Cipolla-Neto,Solange Castro Afeche

    Anhydroecgonine methyl ester (AEME), also called methylecgonidine, is a pyrolysis product of crack cocaine that is neurotoxic and potentiates cocaine-induced sensitization. The sensitization induced by drugs of abuse can be influenced by melatonin, a neuroprotective pineal hormone. In the same way, drugs of abuse like alcohol and methamphetamine can modify melatonin synthesis. The aim of the present work was to investigate the AEME effects on melatonin synthesis in the rat pineal gland. Neurotransmitter systems involved in its effects, antioxidant enzyme activities and the melatonin protective role in AEME-induced toxicity were also evaluated. The animals were injected with AEME i.p. (1.12 mg per kg of body weight per day) or vehicle for 10 consecutive days and the nocturnal pineal melatonin synthesis profile and SOD, GPx and GR activities in the cerebral cortex and hippocampus were assessed. Cultured pineal glands were incubated with AEME for 30 min or 48 h before norepinephrine stimulation and melatonin synthesis, arylalkylamine N-acetyltransferase activity, cAMP and [Ca2+]i were determined. The involvement of cholinergic and glutamatergic systems was analyzed using different antagonists. The protective role of melatonin in AEME toxicity on hippocampal neurons was evaluated by a viability assay. AEME impaired melatonin synthesis both in vivo and in vitro and this effect seems to be mediated by muscarinic receptors and [Ca2+]i elevation. AEME reduced neuronal viability and melatonin was able to protected hippocampal neurons against AEME toxicity. The melatonin synthesis impairment observed could lead to the worsening of the direct AEME neurotoxicity and to the exacerbation of the crack cocaine addiction and sensitization.

    更新日期:2019-11-01
  • Coal combustion related fine particulate matter (PM2.5) induces toxicity in Caenorhabditis elegans by dysregulating microRNA expression.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-24
    Qiuli Wu,Xiaoxiao Han,Di Wang,Fang Zhao,Dayong Wang

    We employed an in vivo assay system of Caenorhabditis elegans to determine if and which microRNAs (miRNAs) were dysregulated upon exposure to coal combustion related fine particulate matter (PM2.5) by profiling the miRNAs using SOLiD sequencing. From this, expression of 25 miRNAs was discovered to become dysregulated by exposure to PM2.5. Using the corresponding C. elegans deletion mutants, 5 miRNAs (mir-231, mir-232, mir-230, mir-251 and mir-35) were found to be involved in the control of PM2.5 toxicity. Furthermore, mutation of mir-231 or mir-232 induced a resistance to PM2.5 toxicity, whereas mutation of mir-230, mir-251, or mir-35 induced a susceptibility to PM2.5 toxicity. SMK-1, an ortholog of the mammalian SMEK protein, was identified as a molecular target for mir-231 in the regulation of PM2.5 toxicity. In addition, the genes of sod-3, sod-4 and ctl-3, which are necessary for protection against oxidative stress, were determined to be important downstream targets of smk-1 in the regulation of PM2.5 toxicity. The triggering of this mir-231-SMK-1-SOD-3/SOD-4/CTL-3 signaling pathway may be a critical molecular basis for the role of oxidative stress in the induction of coal combustion related PM2.5 toxicity.

    更新日期:2019-11-01
  • Mitochondria and MAPK cascades modulate endosulfan-induced germline apoptosis in Caenorhabditis elegans.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-17
    Jingjing Wang,Hua Du,Yaguang Nie,Yun Wang,Hui Dai,Mudi Wang,Dayan Wang,An Xu

    Endosulfan as a new member of persistent organic pollutants has been shown to induce apoptosis in various animal models. However, the mechanism underlying endosulfan-induced apoptosis has not been well elucidated thus far. Caenorhabditis elegans N2 wild type and mutant strains were used in the present study to clarify the roles of the mitochondria, the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway, and mitogen-activated protein kinase (MAPK) cascades in α-endosulfan-induced apoptosis. Our results demonstrated a dose- and time-dependent increase of apoptosis in the meiotic zone of the gonad of C. elegans exposed to graded concentrations of endosulfan. The expression levels of sod-3, localized in the mitochondrial matrix, increased greatly after endosulfan exposure. A significant increase in germ cell apoptosis was observed in abnormal methyl viologen sensitivity-1 (mev-1(kn-1)) mutants (with abnormal mitochondrial respiratory chain complex II and higher ROS levels) compared to that in N2 at equal endosulfan concentrations. We found that the insulin/IGF-1 signaling pathway and its downstream Ras/ERK/MAPK did not participate in the endosulfan-induced apoptosis. However, the apoptosis in the loss-of-function strains of JNK and p38 MAPK signaling pathways was completely or mildly suppressed under endosulfan stress. The apoptotic effects of endosulfan were blocked in the mutants of jnk-1/JNK-MAPK, sek-1/MAP2K, and pmk-1/p38-MAPK, suggesting that these downstream genes play an essential role in endosulfan-induced germ cell apoptosis. In contrast, the mkk-4/MAP2K and nsy-1/MAP3K were only partially involved in the apoptosis induction. Our data provide evidence that endosulfan increases germ cell apoptosis, which is regulated by mitochondrial function, JNK and p38 MAPK cascades. These findings contribute to the understanding of the signal transduction pathways involved in endosulfan-induced apoptosis.

    更新日期:2019-11-01
  • Circulating levels of miR-122 increase post-mortem, particularly following lethal dosing with pentobarbital sodium: implications for pre-clinical liver injury studies.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-11
    Joanna I Clarke,Shiva Seyed Forootan,Jonathan D Lea,Lawrence S Howell,Josep Monne Rodriguez,Anja Kipar,Christopher E Goldring,B Kevin Park,Ian M Copple,Daniel J Antoine

    microRNA-122 (miR-122) is increasingly being measured in pre-clinical and clinical settings due to greater sensitivity and hepatic specificity compared to the gold standard liver injury biomarker alanine aminotransferase (ALT). In pre-clinical studies, various culling methods can be employed prior to collection of blood samples, including lethal injection with pentobarbital sodium (Pentoject). However, little is known about whether such an approach could alter the circulating levels of miR-122 and compromise the interpretation of data. We therefore exposed C57BL/6J mice to saline or the model hepatotoxin paracetamol and collected blood samples pre-cull (via tail bleed) and post-cull (via cardiac puncture following exposure to a rising concentration of CO2 or intraperitoneal injection of Pentoject). Compared to pre-cull levels there was a significant increase in serum miR-122 level in mice culled with CO2 and, to a much greater extent, in mice culled with Pentoject. As a result, whilst the serum level of miR-122 increased in Pentoject-culled animals exposed to paracetamol, the higher level in saline-treated mice rendered this difference statistically non-significant, in contrast to findings in animals culled with CO2. ALT levels were unaffected by sacrifice method. Consistent with the in vivo findings, exposure of primary mouse hepatocytes to Pentoject provoked a rapid and concentration-dependent release of miR-122 into the culture media. Thus, for optimal design and interpretation of data from pre-clinical liver injury studies in which miR-122 is to be used as a biomarker, we recommend that blood samples are collected pre-cull whenever possible, and that lethal injection with Pentoject is avoided.

    更新日期:2019-11-01
  • Toxic mechanisms of microcystins in mammals.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-24
    Nicole L McLellan,Richard A Manderville

    Microcystins, such as microcystin-leucine arginine (MC-LR), are some of the most toxic and prevalent cyanotoxins produced by cyanobacteria in freshwater and saltwater algal blooms worldwide. Acute and chronic exposures to microcystins are primarily known to cause hepatotoxicity; cellular damage and genotoxicity within mammalian livers. However, in vivo studies indicate that similar damage may occur in other mammalian organs and tissues, such as the kidney, heart, reproductive systems, and lungs - particularly following chronic low-dose exposures. Mechanisms of toxicity of mycrocystins are reviewed herein; including cellular uptake, interaction with protein phosphatases PP1 and PP2A, cytoskeletal effects, formation of oxidative stress and induction of apoptosis. In general, the mode of action of toxicity by MCs in mammalian organs are similar to those that have been observed in liver tissues. A comprehensive understanding of the toxic mechanisms of microcystins in mammalian tissues and organs will assist in the development of risk assessment approaches to public health protection strategies and the development of robust drinking water policies.

    更新日期:2019-11-01
  • Assessment of cadmium-induced nephrotoxicity using a kidney-on-a-chip device.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-04-25
    Zhongyu Li,Lei Jiang,Tingting Tao,Wentao Su,Yaqiong Guo,Hao Yu,Jianhua Qin

    Cadmium (Cd) is a common environmental pollutant. Its effects on human health have attracted great attention. The kidney is the organ that is the most affected by Cd exposure. Thus, it is highly desirable to develop a reliable model to evaluate Cd-induced nephrotoxicity in vitro. We present a kidney-on-a-chip with three compartmentalized culture chambers to examine Cd-induced nephrotoxicity. The culture and collection channels represent the capillary and the glomerular capsule sides of the glomerular filtration barrier, respectively. Isolated primary rat glomerular endothelial cells (GECs) were cultured on the side surface of the middle gel channel. The integrated GEC layer demonstrated the selective permeability of the renal barrier. Therefore, it was further utilized to study the nephrotoxicity induced by Cd exposure at different concentrations. Cd induced significant cytotoxicity and disrupted the expression of tight junction protein ZO-1 in a dose-dependent manner. Moreover, Cd exposure increased the permeability of the endothelial layer to large molecules, immunoglobulin G and albumin. These results facilitate the understanding of the underlying mechanism of kidney dysfunction and glomerular disease. This is the first study on Cd-induced nephrotoxicity using primary GECs in a microfluidic device. The kidney-on-a-chip device enables direct visualization and quantitative analysis of GEC responses to Cd in real time. It may provide a micro-scale platform based on the human system for nephrotoxicity testing under varying environmental exposure.

    更新日期:2019-11-01
  • LncRNA-MALAT1 as a novel biomarker of cadmium toxicity regulates cell proliferation and apoptosis.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-03-17
    Qinhai Huang,Qian Lu,Baoxin Chen,Huanyu Shen,Qun Liu,Zhiheng Zhou,Yixiong Lei

    Cadmium (Cd) and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not well understood. This study aimed to investigate whether lncRNA-MALAT1 could serve as a novel biomarker of Cd toxicity in cells, animals and Cd-exposed workers, and regulate cell proliferation, apoptosis, migration and invasion. MALAT1 expression increased gradually in CdCl2 transformed 16HBE cells. The cell apoptosis, migration and invasion were significantly inhibited, and the mRNA and protein expression of FOXC2, STAT, BAX, EGFR, and TGF-β1 reduced, but BCL-2 increased (P < 0.05) after silencing MALAT1 by siRNA in CdCl2 treated 16HBE cells of 15th and 35th passages. Cadmium increased MALAT1 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood MALAT1 expression and urinary/blood Cd concentrations, and there were significant correlations of MALAT1 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. This study suggests that the expression of MALAT1 is upregulated and regulates the cell cycle progression, proliferation, apoptosis, migration and invasion in Cd toxicity. MALAT1 may serve as a novel valuable biomarker of cadmium exposure and cadmium toxicity.

    更新日期:2019-11-01
  • Nonylphenol induces pancreatic damage in rats through mitochondrial dysfunction and oxidative stress.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-03-17
    Xueji Li,Liting Zhou,Yiping Ni,Aiqing Wang,Mingjiang Hu,Yao Lin,Chengjiao Hong,Jianmei Wan,Bin Chen,Lijun Fang,Jian Tong,Xing Tong,Shasha Tao,Hailin Tian

    The organic alkylphenol 4-nonylphenol (NP) is regarded to be an endocrine disrupting chemical (EDC), one of the widely diffused and stable environmental contaminants. Due to its hydrophobicity and long half-life, NP can easily accumulate in living organisms, including humans, where it displays a series of toxic effects. It has been widely reported that NP affects male reproduction. In addition, there is increasing evidence suggesting that NP is detrimental to various organs, including the pancreas. This study investigated the adverse effects of NP exposure on the pancreas. Sprague-Dawley rats were treated with different doses of NP for 90 consecutive days. The data suggested that the body weights of the rats treated with NP decreased, and the highest dose of NP treatment (180 mg kg-1) dramatically increased water consumption by rats. Meanwhile, H&E staining and immunohistochemistry indicated that islets in the pancreases shrunk when the rats were treated with the indicated doses of NP. TUNEL staining demonstrated that NP exposure up-regulated the level of apoptosis in the pancreases in a dose-dependent manner. Besides this, NP exposure inhibited the secretion of insulin and disrupted glucose tolerance. The levels of reactive oxygen species (ROS) and intracellular calcium ([Ca2+]i) in the islets were up-regulated in the groups of rats treated with NP, but the levels of Mitochondrial Membrane Potential (MMP) were down-regulated. These results suggest that NP-induced pancreatic damage in rats occurs through mitochondrial dysfunction and oxidative stress, which causes disruption of glucose tolerance and decrease in insulin secretion.

    更新日期:2019-11-01
  • Zinc oxide nanoparticle induced age dependent immunotoxicity in BALB/c mice.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-03-15
    Violet Aileen Senapati,Govind Sharan Gupta,Alok Kumar Pandey,Rishi Shanker,Alok Dhawan,Ashutosh Kumar

    Zinc oxide (ZnO) nanoparticles (NPs) have potential applications in cosmetics, food packaging and biomedicine but concerns regarding their safety need to be addressed. In the present study, the immunotoxic potential of ZnO NPs was evaluated in different ages of BALB/c mice after sub-acute exposure. The cytokine release, immunophenotyping, distribution of ZnO NPs and ultrastructural changes were assessed. A significant (p < 0.05) change in the CD4- and CD8-cells, levels of IL-6, IFN-γ and TNF-α and reactive oxygen species were observed in aged mice. In juvenile mice, increase in reactive oxygen species and IL-6 and TNF-α levels was observed with no significant changes in adult mice. A significant (p < 0.05) increase in the expression levels of mitogen activated protein kinase (MAPK) cascade proteins such as phospho-ERK1/2, phospho-JNK and phospho-p38 were also induced in aged mice. Collectively, our results indicate that the aged mice are more susceptible to ZnO NP induced immunotoxicity.

    更新日期:2019-11-01
  • DNA damage in the elderly is associated with 5-MTHF levels: a pro-oxidant activity.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-03-13
    Marília Baierle,Gabriela Göethel,Sabrina N Nascimento,Mariele F Charão,Angela M Moro,Natália Brucker,Elisa Sauer,Bruna Gauer,Caroline Souto,Juliano Durgante,Marcelo Dutra Arbo,Solange Cristina Garcia

    The aging phenomenon is associated with oxidative stress damage in biomolecules, especially DNA. 5-Methyltetrahydrofolate (5-MTHF), the active folate form, plays a pivotal role in maintaining genomic integrity. However, recently it was associated with cancer development. In Brazil, there are folic acid enriched foods, such as flour, making the general population chronically exposed to folates. Therefore, the aim of this study was to investigate whether erythrocytes 5-MTHF levels were associated with age-related DNA damage in two groups (elderly and young subjects). Additionally, a study in Caenorhabditis elegans, an in vivo alternative model, was performed to verify if 5-MTHF presents a pro-oxidant effect. A total of 50 elderly and 25 young subjects participated in this study, which analyzed whole blood DNA damage, plasma carbonyl proteins (PCO), and erythrocytes 5-MTHF levels. In addition, ROS and RNS production, survival rate, and lifespan were performed in C. elegans exposed to 5-MTHF. Blood 5-MTHF levels and DNA damage were increased in the elderly compared to the young group. A positive association was found between 5-MTHF levels and DNA damage, and between DNA damage and PCO levels, suggesting an oxidative cause of damage associated with the active folate form. In an experimental study it was observed that 5-MTHF increased ROS production in C. elegans, in a dose dependent manner, while survival rate and life span were not affected at the test doses. These findings suggest that 5-MTHF, the active folate form, may be involved in DNA damage in the elderly. This damage could be a result of oxidative stress, as observed in the in vivo alternative model; however, more studies are necessary to prove our present results.

    更新日期:2019-11-01
  • Chromium contributes to human bronchial epithelial cell carcinogenesis by activating Gli2 and inhibiting autophagy.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-02-15
    Junpeng Huang,Gang Wu,Rong Zeng,Jinting Wang,Rui Cai,James Chung-Man Ho,Jiren Zhang,Yanfang Zheng

    Occupational and environmental inhalation exposure to hexavalent chromium [Cr(vi)] compounds has been confirmed to cause respiratory system injury and cancer. The molecular mechanisms of chromium carcinogenesis still require further study. We established Cr(vi)-transformed cells (BEAS-2B-Cr) after chronic exposure of immortalized normal human bronchial epithelial BEAS-2B cells to low doses of Cr(vi), which obtained the ability of anchorage-independent growth. BEAS-2B-Cr cells not only exhibited stronger proliferation, migration, invasion and tumorigenesis capabilities but also acquired an altered and distinct Gli2 gene expression pattern compared with untreated parental BEAS-2B cells (P-NC) and the control BEAS-2B cells (NC). Interestingly, we found that activation of Gli2 by Cr(vi) treatment prevented the induction of autophagy. Using a gene silencing approach, we showed that Gli2 plays an important role in the malignant properties of BEAS-2B-Cr cells. Downregulation of Gli2 induced autophagy and inhibited cell proliferation and colony forming abilities, which are both upregulated in BEAS-2B-Cr cells compared to NC cells. In addition, inhibition of autophagy by 3-methyladenine (3-MA) partially suppressed the cytotoxicity induced by GANT61-induced inhibition of Gli2. These results demonstrate that hexavalent chromium Cr(vi) activates Gli2 to promote the proliferation of BEAS-2B-Cr cells by inhibition of autophagy, which contributes to human bronchial epithelial cell carcinogenesis. Gli2 may not only play an important role in lung cancer pathogenesis, but also be a promising early indicator in monitoring exposure to chromium.

    更新日期:2019-11-01
  • Downregulation of catalase by CuO nanoparticles via hypermethylation of CpG island II on the catalase promoter.
    Toxicol. Res. (IF 1.593) Pub Date : 2017-02-09
    Sandesh Chibber,Amee Sangeet,Shakeel Ahmed Ansari

    The advent of nanotechnology has led to new applications of copper as antibiotic treatment alternatives, nanocomposite coatings, catalysts, and lubricants among others. However, few studies address the impact of nano-size copper on the molecular mechanism of eukaryotic cells. Therefore, in the present study, the human hepatic cell line (WRL-68) was used to evaluate the molecular mechanism involved in the adverse effect of CuO NPs. CuO NPs were characterized by scanning electron microscopy and dynamic light scattering to confirm their 100 nm size and their purity was determined by Fourier transform infra-red spectroscopy. The side scattered intensity in WRL-68 cells at a CuO NP concentration of 250, 500, 750 and 1000 μM was found to be 108.83%, 126.86%, 189.03% and 250.88% respectively. The reactive oxygen species (ROS) generation at a CuO NP concentration of 1000 μM in WRL-68 cells was 417.75%. Moreover, the ROS induced methylation of CpG island II on the catalase promoter and downregulated catalase expression at the transcriptional level in WRL-68 cells. Furthermore, the activity of the catalase enzyme was found to decrease with an increase in concentration of CuO NPs. Subsequently, the proliferation of the WRL-68 cells was increased on exposure to the CuO NPs as demonstrated by the mitochondrial activity in the MTT assay. Conclusively, it is demonstrated that exposure of CuO NPs at 1000 μM for 24 h in the WRL-68 cell induced methylation of CpG island II via ROS on the catalase promoter and downregulated catalase expression at the transcriptional level. The obtained molecular mechanistic insights described adverse effects related to the CuO NPs.

    更新日期:2019-11-01
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