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Toxicology Letters

Samah R Khalil, Amany Tharwat Mohammed, Amir H Abd-Elfatah, Asmaa W Zaglool
The aim of this study was to explore the potential effects of quercetin (QUR) on doxorubicin (DOX)-induced nephrotoxicity. Fifty male rats were assigned to five groups (10 rats each): a control group, a DOX-treated group (total dose, 15 mg/kg bw, intraperitoneally), a QUR-treated group (50 mg/kg bw/day, orally), a prophylaxis co-treated group, and a therapeutic co-treated group. Biochemical parameters and renal function were measured. Moreover, kidney tissues were homogenized for inflammatory marker evaluation and real-time qPCR analysis to determine the changes in intermediate filament protein mRNA levels (desmin, vimentin, connexin 43 and nestin)...
February 20, 2018: Toxicology Letters
Angelika Langsch, Raymond M David, Steffen Schneider, Saskia Sperber, Volker Haake, Hennicke Kamp, Edgar Leibold, Bennard van Ravenzwaay, Rainer Otter
Hexamoll® DINCH is an important alternative to phthalate plasticizers. Although regulatory reviews have not identified any potential hazards even in sensitive populations, an in vitro study by Campioli et al. (2015) suggested Hexamoll® DINCH might alter fat storage in adipocytes resulting in obesity. To evaluate this hypothesis, data from studies with Hexamoll® DINCH were reviewed for evidence of deposition in fat, changes in body weight, or changes in serum chemistry reflecting altered metabolic status...
February 20, 2018: Toxicology Letters
Changwen Zhang, Penghao Li, Yingwu Wen, Guowei Feng, Yu Liu, Yangyi Zhang, Yong Xu, Zhihong Zhang
Antimony is a widely used heavier pnictogens in industry, and its toxicity has been a matter of concern. Although previous studies have suggested that antimony may have the function as either a tumor suppressor or an oncogene in several cancers, the molecular basis underlying antimony-mediated transformation is still unclear. In the current study, we attempt to elucidate the potential role of antimony in the development of prostate cancer. Our results showed that the concentration of antimony was much higher in serum of prostate cancer patients, and was closely associated with poor outcome of patients who underwent radical prostatectomy...
February 17, 2018: Toxicology Letters
Brice Oulion, James S Dobson, Christina N Zdenek, Kevin Arbuckle, Callum Lister, Francisco C P Coimbra, Bianca Op den Brouw, Jordan Debono, Aymeric Rogalski, Aude Violette, Rudy Fourmy, Nathaniel Frank, Bryan G Fry
Atractaspis snake species are enigmatic in their natural history, and venom effects are correspondingly poorly described. Bite reports are scarce but bites have been described as causing severe hypertension, profound local tissue damage leading to amputation, and deaths are on record. Clinical descriptions have largely concentrated upon tissue effects, and research efforts have focused upon the blood-pressure affecting sarafotoxins. However, coagulation disturbances suggestive of procoagulant functions have been reported in some clinical cases, yet this aspect has been uninvestigated...
February 17, 2018: Toxicology Letters
Dan Wang, Huali Yang, Zheng Zhou, Man Zhao, Runsheng Chen, Simon H Reed
Due to the specific antimicrobial activity of silver nanoparticles (AgNPs), they are widely used in wound dressings, coatings in medical devices and household products. In spite of the well-documented genotoxicity of AgNPs, the molecular mechanisms of relieving AgNP-induced DNA damage stress remain poorly understood. We report here that one of the DNA repair factors, XPF, plays a crucial role in resisting AgNP-induced DNA damage stress in human cells. Following culture with AgNP-containing media, severely decreased colony forming abilities have been observed in XPF mutant and knockdown cells compared with wild type or control cells respectively, demonstrating that XPF is required to resist the AgNP-induced stress...
February 17, 2018: Toxicology Letters
Hui-Ying Li, Lei Xing, Jia-Qi Wang, Nan Zheng
AIM: Furosine is one of the Maillard reaction products (MRPs) and is found in a variety of heat-processed food. Yet its toxicity is still unclear. The present study was designed to assess furosine toxicity in cell models and in CD-1 mice, respectively. METHODS: In vitro, the effects of furosine on the cell viability, cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and evaluated, sensitive cell lines and proper dosage of furosine for further animal experiment were determined, and the mechanisms of toxicity were explored...
February 16, 2018: Toxicology Letters
Xiao Xu Bai, Li Gu, Hui Min Yang, Shao Song Xi, Ning Xia, Song Zhang, Hong Zhang
Clinical epidemiological studies have shown that there is a link between Parkinson's disease (PD) and cancer, but how PD regulates cancer development remains unknown. In our study, the effect of metabotropic glutamate receptor 5 (mGlu5 ) on hepatoma was explored in a rotenone-induced PD model both in vitro and in vivo. We found that conditioned media derived from MN9D dopaminergic neuronal cells by rotenone-induced toxicity inhibited the growth, migration, invasion and promoted apoptosis of Hepa1-6 cells, which corresponded with decreased expression of mGlu5 ...
February 16, 2018: Toxicology Letters
Yoshinori Okamoto, Akira Aoki, Koji Ueda, Hideto Jinno
Estrogen is reported to be involved in mammary tumorigenesis. To unveil metabolic signatures for estrogen-induced mammary tumorigenesis, we carried out serum metabolomic analysis in an estrogen-induced mammary tumor model, female August Copenhagen-Irish/Segaloff (ACI/Seg) rats, using liquid chromatography-mass spectrometry. In contrast to the control group, all rats with an implanted 17β-estradiol (E2) pellet developed mammary tumors during this experiment. E2 treatment significantly suppressed body weight gain...
February 15, 2018: Toxicology Letters
Donna A Glinski, W Matthew Henderson, Robin J Van Meter, S Thomas Purucker
Understanding how pesticide exposure to non-target species influences toxicity is necessary to accurately assess the ecological risks these compounds pose. To assess the potential metabolic activation of broad use pesticides in amphibians, in vitro and in vivo metabolic rate constants were derived from toad (Anaxyrus terrestris) livers in experiments measuring the depletion of atrazine (ATZ), triadimefon (TDN), and fipronil (FIP) as well as formation of their metabolites. To determine the predictability of these in vitro derived rate constants, Fowler's toads (Anaxyrus fowleri) were exposed to soil contaminated with each of the pesticides at maximum application rate...
February 13, 2018: Toxicology Letters
Meiyuan Yang, Yaobin Li, Ying Wang, Nuo Cheng, Yi Zhang, Shimin Pang, Qiwei Shen, Lijuan Zhao, Guilin Li, Gaochun Zhu
Lead (Pb) is an environmental neurotoxic metal. Chronic exposure to Pb causes deficits of learning and memory in children and spatial learning deficits in developing rats. In this study we investigated the effects of Pb exposure on the expression of HMGB1 and HO-1 in rats and PC12 cells. The animals were randomly divided to three groups: control group; low lead exposure group; high lead exposure group; PC12 cells were divided into 3 groups: 0 μM (control group), 1 μM and 100 μM Pb acetate. The results showed that Pb levels in blood and brain of Pb exposed groups were significantly higher than that of the control group (p < 0...
February 12, 2018: Toxicology Letters
Xiaohong Hou, Dan Huang, Qinghe Meng, Qi Zhang, Lixia Jia, Siqi Wang, Zhiyuan Cheng, Shuang Wu, Lanqin Shang, Jianjun Jiang, Weidong Hao
Chlorocholine chloride (CCC) is widely used to regulate plant growth. Considerable attention has been focused on its reproductive and developmental toxicities. In order to investigate the effects of pubertal CCC exposure on testicular testosterone (T) synthesis, male SD rats were exposed to CCC by oral gavage at doses of 0, 75, 150 and 300 mg/kg bw/day from postnatal day 23 to 70. We observed that pubertal CCC exposure lowered the body weight and the mean Johnsen's score. The percentage of seminiferous tubules with deciduous spermatogenic cells was increased in the 75 and 150 mg/kg bw/day groups...
February 12, 2018: Toxicology Letters
Xiuhua Yu, Haolan Yu, Ningning Jiang, Xiuyun Zhang, Mengmeng Zhang, Hui Xu
Exposure to fluoride from environmental sources remains an overlooked, but serious public health risk. In this study, we looked into the role osteocytes play on the mechanism underlying fluoride induced osteopathology. We analyzed bone formation and resorption related genes generated by osteocytes that were exposed to varied doses of fluoride with and without PTH in vitro. Correspondingly, osteogenesis and osteoclastogenesis related genes were also investigated in rats exposed to fluoride for 8 weeks, and the PTH(1-34)was applied at the last 3 weeks to observe its role in regulating bone turnover upon fluoride treatment...
February 12, 2018: Toxicology Letters
Zehe Ge, Haipeng Diao, Xiaoli Ji, Qingping Liu, Xiaoyan Zhang, Qing Wu
Cadmium (Cd), a toxic heavy metal, is known to induce renal toxicity by primarily targeting at renal proximal tubule. Endoplasmic reticulum (ER) stress and gap junctional intercellular communication (GJIC) regulate many pathophysiological processes. Yet, how ER stress and GJIC regulate Cd-induced nephrotoxicity remain elusive. In this study, we treated human proximal tubule (HK-2) cells with 1 μM CdCl2every other day for 12 days and found that Cd significantly increased cell apoptosis at 10 and 12 days. This cytotoxicity correlated with activation of ER stress and apoptotic signaling evidenced by upregulation of inositol-requiring enzyme 1 (IRE1α), splice X-box binding protein-1 (XBP-1s), and apoptosis signal-regulating kinase 1 (ASK1) proteins...
February 11, 2018: Toxicology Letters
Shengwei Xiong, Chunhong Huang
Synergism is a significant phenomenon present in snake venoms that may be an evolving strategy to potentiate toxicities. Synergism exists between different toxins or toxin complexes in various snake venoms, with phospholipaseA 2 s (PLA 2 s) (toxins or subunits) the main enablers. The predominant toxins, snake venom PLA 2 s, metalloproteases (SVMPs), serine proteases (SVSPs) and three-finger toxins (3FTxs), play essential roles in synergistic processes. The hypothetical mechanisms of synergistic effect can be generalized under the effects of amplification and chaperoning...
February 8, 2018: Toxicology Letters
Xiaoqi Pan, Xu Wu, Dandan Yan, Cheng Peng, Chaolong Rao, Hong Yan
Acrylamide (ACR) is a classic neurotoxin in animals and humans. However, the mechanism underlying ACR neurotoxicity remains controversial, and effective prevention and treatment measures against this condition are scarce. This study focused on clarifying the crosstalk between the involved signaling pathways in ACR-induced oxidative stress and inflammatory response and investigating the protective effect of antioxidant N-acetylcysteine (NAC) against ACR in PC12 cells. Results revealed that ACR exposure led to oxidative stress characterized by significant increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels and glutathione (GSH) consumption...
February 6, 2018: Toxicology Letters
Schreier Cassandra, Rothmiller Simone, Scherer A Michael, Rummel Christoph, Steinritz Dirk, Thiermann Horst, Schmidt Annette
INTRODUCTION: The chemical warfare agent sulfur mustard (SM), also known as mustard gas, was first used in World War I. Although prohibited by the chemical warfare convention, significant amounts of SM still exist and have still to be regarded as a threat for military personnel and civilians. After SM exposure, the most prominent clinical symptom is the development of extensive non-healing skin wounds. This chronic wound healing dysfunction is persisting over long time. Mesenchymal stem cells (MSC) are known to play an important role in wound healing...
February 6, 2018: Toxicology Letters
Yao Xu, Yong Li, Limei Ma, Guang Xin, Zeliang Wei, Zhi Zeng, Zhihua Xing, Shiyi Li, Hai Niu, Wen Huang
Cataract is the leading cause of blindness with an estimated 16 million people affected worldwide. d-Galactose (d-gal) is a reducing sugar that widely distributed in foodstuffs, and studies show that d-gal could promote cataract formation by damaging nature lens epithelial cells (LECs). However, the underlying mechanism is unclear. In our present study, d-gal resulted in premature senescence of LECs, which was confirmed by determining the β-galactosidase activity, cell proliferative potential and cell cycle distribution, though apoptosis of LECs was not observed...
February 6, 2018: Toxicology Letters
Lu Wen, Qiu-Shuang Zhang, Yang Heng, Ying Chen, Shuo Wang, Yu-He Yuan, Nai-Hong Chen
Ample evidence shows that Parkinson's disease (PD) is more than simply a central nervous system (CNS) disorder: the immune system appears to participate in PD pathogenesis. Extracellular misfolded α-synuclein (α-syn) may trigger an inflammatory response in the brain. Abnormal immune responses are involved in the development of PD, but little is known about the relationship between the thymus malfunction and the pathogenesis of PD. The present study investigated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced impairment in thymus and explored possible mechanisms involved in PD pathogenesis...
February 5, 2018: Toxicology Letters
E Razzuoli, G Mignone, F Lazzara, W Vencia, M Ferraris, L Masiello, B Vivaldi, A Ferrari, E Bozzetta, M Amadori
We tested cadmium (Cd2+) effects on porcine IPEC-J2 cells, which represent an in vitro model of the interaction between intestinal cells and both infectious and non-infectious stressors. Accordingly, we investigated the effects of low (2 μM) to moderate (20 μM) concentrations of Cd2+, in terms of pro-inflammatory gene expression and protein release, as well as of infectivity in a Salmonella typhimurium penetration model. Our data showed a significant (P < .001) increase of intracellular Cd2+ after 3, 6 and 24 h of exposure with respect to levels at 1 h...
February 5, 2018: Toxicology Letters
Anika Engel, Thorsten Buhrke, Stefanie Kasper, Anne-Cathrin Behr, Albert Braeuning, Sönke Jessel, Albrecht Seidel, Wolfgang Völkel, Alfonso Lampen
DINCH® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH®, there are almost no toxicological data available regarding its primary and secondary metabolites...
February 5, 2018: Toxicology Letters
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