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Chang Feng, Sisi Liu, Fankun Zhou, Yanyan Gao, Yanshu Li, Guihua Du, Ying Chen, Huan Jiao, Jiangao Feng, Yuanyuan Zhang, Dandan Bo, Zongguang Li, Guangqin Fan
A large number of studies have evidenced that developmental neurotoxicity induced by lead (Pb) is related to oxidative injury. Furthermore, recent studies have found that developmental Pb exposure can induce neurodegeneration in old age. Because of the common presence of Pb in the environment, humans are exposed to this metal throughout their lifetime. However, few studies have explored the changes in lifespan profiles of neurotoxicity, as well as oxidative stress following lifetime Pb exposure. In the present study, rats were exposed to lead acetate from their embryonic stage to old age...
November 13, 2018: Toxicology
Yuko Watanabe, Risako Tajiki-Nishino, Hitoshi Tajima, Tomoki Fukuyama
Recent studies have shown that the estrogen receptor α (ERα), but not ERβ, is involved in the proinflammatory and propruritic responses in cutaneous allergy. In addition, results from our recent study showed that while oral administration of the rather ERβ-selective agonist bisphenol A exacerbated the respiratory allergic inflammation, the potential inflammatory reaction in the skin was decreased after administration of bisphenol A. This study aimed to elucidate whether ERα and ERβ are involved in the progression of an allergic airway inflammation...
November 13, 2018: Toxicology
Ondřej Zapletal, Jiřina Procházková, Vít Dubec, Jiřina Hofmanová, Alois Kozubík, Jan Vondráček
Butyrate helps to maintain colon homeostasis and exhibits chemopreventive effects in colon epithelium. We examined the interactive effects of butyrate and benzo[a]pyrene (BaP), dietary carcinogen, in regulation of expression of a panel of phase I and II xenobiotic metabolizing enzymes (XMEs) in human colon cells. In human colon carcinoma HCT-116 and HT-29 cell lines, butyrate alone increased mRNA levels of some enzymes, such as N-acetyltransferases (in particular NAT2). In combination with BaP, butyrate potentiated induction of cytochrome P450 family 1 enzymes (CYP1A1), aldo-keto reductases (AKR1C1) or UDP-glucuronosyltransferases (UGT1A1)...
November 12, 2018: Toxicology
Hisham A Alhadlaq, Mohd Javed Akhtar, Maqusood Ahamed
Manganese (IV) oxide nanoparticles (MnO2 NPs) are increasingly used in numerous applications. Multiple applications of MnO2 NPs, however, increase the human exposure and thus potential risk related to their toxicity. There is little information regarding the toxicity mechanisms of MnO2 NPs in human cells. In this study, we explored the toxic potential of MnO2 NPs in human breast cancer epithelial (MCF-7) and human fibrosarcoma epithelial (HT1080) cells in order to examine whether epithelial cells of different origins showed similar responses...
November 3, 2018: Toxicology
Jiawei Huang, Yu Lu, Bin Zhang, Shaoping Yang, Qian Zhang, Haiyan Cui, Xianxian Lu, Yun Zhao, Xu Yang, Rui Li
The toxicity of formaldehyde (FA) has always been of great concern, particularly since its use is unavoidable. On the other hand, epigallocatechin-3-gallate (EGCG), an active substance in tea polyphenols, has been shown to demonstrate physiological protective functions by in both epidemiological and zoological studies, particularly in the nervous system. The study described here, aims to explore whether EGCG can alleviate the neurotoxic effects induced by formaldehyde. After 14 days of exposure to 3 mg/m3 formaldehyde, mice exhibited significant cognitive impairment...
November 2, 2018: Toxicology
Yao Lv, Yinghui Fang, Panpan Chen, Yue Duan, Tongliang Huang, Leikai Ma, Lubin Xie, Xianwu Chen, Xiaofang Chen, Jimin Gao, Ren-Shan Ge
Dicyclohexyl phthalate (DCHP) is a phthalate plasticizer with a ring structure in the alcohol moiety. The objective to the current study was to determine the effects of DCHP on Leydig cell regeneration in the adult rat-testis. Adult male Sprague Dawley rats received intraperitoneally an injection of ethane dimethane sulfone (EDS) to eliminate all Leydig cells in the testis and then were divided into 4 groups of 0 (control), 10, 100, and 1000 mg/kg/day DCHP. Rats were gavaged either vehicle (corn oil, control) or DCHP from post-EDS day 7 to day 21 and 28...
November 1, 2018: Toxicology
Donatella Degl'Innocenti, Matteo Ramazzotti, Erica Sarchielli, Daniela Monti, Marta Chevanne, Gabriella Barbara Vannelli, Emanuela Barletta
Exposure to herbicides can induce long-term chronic adverse effects such as respiratory diseases, malignancies and neurodegenerative diseases. Oxadiazon, a pre-emergence or early post-emergence herbicide, despite its low acute toxicity, may induce liver cancer and may exerts adverse effects on reproductive and on endocrine functions. Unlike other herbicides, there are no indications on neurotoxicity associated with long-term exposure to oxadiazon. Therefore, we have analyzed in primary neuronal precursor cells isolated from human striatal primordium (HSP) the effects of non-cytotoxic doses of oxadiazon on neuronal cell differentiation and migration, and on the expression and activity of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) and of the acylphosphatase (ACYP)...
October 31, 2018: Toxicology
Alessandro Attanzio, Anna Frazzitta, Sonya Vasto, Luisa Tesoriere, Anna Maria Pintaudi, Maria Antonia Livrea, Antonio Cilla, Mario Allegra
Cigarette smoking has been linked with oxidative stress and inflammation. In turn, eryptosis, the suicidal erythrocyte death similar to apoptosis that can be triggered by oxidative stress, has been associated with chronic inflammatory diseases including atherosclerosis. However, the link between smoking and eryptosis has not been explored so far. The aim of the present study was to determine the level of eryptotic erythrocytes in healthy male smokers (n = 21) compared to non-smokers (n = 21) and assess its relationship with systemic inflammation (CRP) as well as with antioxidant defense (GSH) and their resistance to ex-vivo induced hemolysis...
October 29, 2018: Toxicology
Samantha Cooper, Hardip Sandhu, Afthab Hussain, Christopher Mee, Helen Maddock
Anti-cancer drug Sunitinib is linked to adverse cardiovascular events, which have shown to involve mitogen activated kinase kinase 7 (MKK7) pathway. Sunitinib-induced cardiotoxicity in 3, 12 and 24 months old male Sprague-Dawley rats and MKK7 expression and activation was investigated using the Langendorff perfused heart model followed by Western blot analysis. Cardiac function and infarct size were measured during/after 125 min of Sunitinib treatment. Left ventricular cardiac samples were analysed by qRT-PCR for expression of MKK7 mRNA and cardiac injury associated microRNAs...
October 26, 2018: Toxicology
Cédric Touvrey, Charlotte Courageux, Virginia Guillon, Raphael Terreux, Florian Nachon, Xavier Brazzolotto
The efficiency of human butyrylcholinesterase (BChE) as a stoichiometric bioscavenger of nerve agents is well established. However, wide use is currently limited by production and purification costs. Aiming at identifying an alternative human protein bioscavenger, we looked for an original scaffold candidate by virtual screening of the Protein Data Bank for functional similarity using the "Surfing the Molecules" software ( and a search model based on the BChE active site topology...
October 22, 2018: Toxicology
Armin Salek-Maghsoudi, Shokoufeh Hassani, Saeideh Momtaz, Amir Shadboorestan, Mohammad Reza Ganjali, Mohammad Hossein Ghahremani, Rohollah Hosseini, Parviz Norouzi, Mohammad Abdollahi
Vaspin, as a newly discovered adipocytokine, can modulate obesity with insulin-sensitizing effects. This study mainly focused on the plasma level of vaspin in insulin resistant rats, which received high-fat diet (HFD) and diazinon (DZN) (70 mg/kg). Upon 30-day experiment, related oxidative stress and inflammatory markers of plasma, the toxic effects of DZN and HFD on the histological structure of the liver, as well as the expression levels of potential genes associated with insulin resistance, phosphatase and tensin homolog (PTEN) and Forkhead box protein O1 (FoxO1) were evaluated...
October 22, 2018: Toxicology
Efthimios Dardiotis, Athina-Maria Aloizou, Vasileios Siokas, Zisis Tsouris, Dimitrios Rikos, Chrysa Marogianni, Michael Aschner, Leda Kovatsi, Dimitrios P Bogdanos, Aristidis Tsatsakis
Organophosphates (OPs) are a class of chemicals commonly used in agriculture as pesticides, that can often lead to severe toxicity in humans. Paraoxonase-1 (PON1) belongs to a family of A-esterases and hydrolyses several OPs while also serving other biological roles. Two main genetic polymorphisms have been shown to affect enzymatic ability; an A > G transition in the 192nd position (192 Q/R, rs662), and an A > T at codon 55 (55 M/L, rs854560). In this review, we searched PubMed for relevant articles published from its inception till June 2018 and included publications from 1996 to 2018...
October 22, 2018: Toxicology
Rui Yang, Min-Jie Guan, Ning Zhao, Ming-Jun Li, Tao Zeng
Our previous study showed that both Kupffer cell eliminator (GdCl3 ) and tumor necrosis factor α (TNF-α) receptor antagonist (etanercept) could partially attenuate binge drinking-induced liver steatosis. Herein, we extended the study by directly investigating the roles of TNF-α on the hepatic fat levels in mice and in HepG2 cells, and explored the underlying mechanisms. SPF male ICR mice were exposed to TNF-α (0.166 mg/kg body weight) with or without phenylisopropyl adenosine (PIA, an anti-lipolytic drug) for 1...
October 22, 2018: Toxicology
Bin Li, Yanan Zhu, Haiyun Chen, Hui Gao, Hangyuan He, Na Zuo, Linguo Pei, Wen Xie, Liaobin Chen, Ying Ao, Hui Wang
This study aimed to demonstrate that prenatal dexamethasone exposure (PDE) can induce kidney dysplasia in utero and adult glomerulosclerosis in male offspring, and to explore the underlying intrauterine programming mechanisms. Pregnant rats were subcutaneously administered dexamethasone 0.2 mg/kg.d from gestational day (GD) 9 to GD20. The male fetus on GD20 and the adult offspring at age of postnatal week 28 were analyzed. The adult offspring kidneys in the PDE group displayed glomerulosclerosis, elevated levels of serum creatinine and urine protein, ultrastructural damage of podocytes, the reduced expression levels of podocyte marker genes, nephrin and podocin...
October 22, 2018: Toxicology
Maiara Bernardes Marques, Patricia Viera de Oliveira, Solange Binotto Fagan, Bruno Rodrigues Oliveira, Bruna Félix da Silva Nornberg, Daniela Volcan Almeida, Luis Fernando Marins, Michael González-Durruthy
In the present study, the molecular docking mechanism based on pharmacodynamic interactions between the ligands AZD1208 and recognized chemotherapy agents (Vincristine and Daunorubicin) with human ATP-binding cassette (ABC) transporters (ABCB1) was investigated. For the first time, were combined an in silico approaches like molecular docking and ab initio computational simulation based on Density Functional Theory (DFT) to explain the drug-drug interaction mechanism of aforementioned chemotherapy ligands with the transmembrane ligand extrusion binding domains (TMDs) of ABCB1...
October 17, 2018: Toxicology
Dai Kakiuchi, Yoshikazu Taketa, Etsuko Ohta, Yasuhiro Fujikawa, Kyoko Nakano-Ito, Shoji Asakura, Satoru Hosokawa
Circulating miR-96-5p, -124-3p, and 183-5p have been reported as safety biomarkers for retinal toxicity. In the present research, 5 serum microRNAs (miRNAs), which are highly specific to and abundant in the retina, including the 3 miRNAs previously mentioned, were assessed in 3 different models of retinal toxicity. Distinct types of retinal lesions were induced in rats by a single dose of N-methyl-N-nitrosourea (MNU: 10, 30, and 50 mg/kg, i.p.), N-methyl-d-aspartate (NMDA: 200 nmol/eye, intravitreal injection), or sodium iodate (NaIO3 : 30 mg/kg, i...
October 16, 2018: Toxicology
Maria Rosa Chitolina Schetinger, Tanara V Peres, Letícia P Arantes, Fabiano Carvalho, Valderi Dressler, Graciela Heidrich, Aaron B Bowman, Michael Aschner
Humans are exposed simultaneously to a variety of neurotoxic agents, including manganese (Mn) and methylmercury (MeHg). Therefore, the study of combined exposures to toxicants is timely. This work aimed to study changes in cholinergic system focusing on acetylcholinesterase (ace-2), monoaminergic system focusing on vesicular monoamine transporter (VMAT, cat-1) expression, to address changes in antioxidant enzymatic systems, namely, the expression of superoxide dismutase (sod-3 and sod-4) and catalase (ctl-3), as well as worm reproduction and locomotion...
October 15, 2018: Toxicology
Eliza Drwal, Agnieszka Rak, Ewa L Gregoraszczuk
Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants, which are released as products of incomplete combustion processes. Harmful effects of PAHs exposure on human health are observed in increased morbidity of respiratory, cardiovascular and immunological diseases. A particularly sensitive group to PAHs exposure are pregnant women and their developing offspring. PAHs can cross the placental barrier and a lot of published data indicated that prenatal or early postnatal exposure to PAHs can lead to developmental toxicity...
October 13, 2018: Toxicology
Jing Si, Rong Zhou, Baoquan Zhao, Yi Xie, Lu Gan, Jinhua Zhang, Yupei Wang, Xin Zhou, Xiaotang Ren, Hong Zhang
The health-related effects of ionizing radiation on embryonic development and their underlying mechanisms are still unclear. The aim of this study was to investigate the role of Wnt signaling in mediating the developmental toxicity induced by heavy ion and proton radiation using zebrafish embryos. Zebrafish embryos were radiated with carbon ions or protons. HLY78, an activator of the Wnt signaling pathway, was added immediately after radiation. Carbon ion radiation induced a significant increase of mortality, and activating Wnt signaling using HLY78 after radiation significantly alleviated this stress...
October 12, 2018: Toxicology
Qun Zeng, Huilan Yi, Liqun Huang, Quan An, Hong Wang
Inorganic arsenic (iAs), a ubiquitous element and a natural drinking water contaminant, has been found to impair male reproductive function. However, the effect of long-term exposure to arsenic on testis damage and its underlying mechanisms still require further evaluation. In the study, male C57BL/6 mice (4 weeks) were treated with sodium arsenite at the doses of 5 or 50 ppm arsenic via drinking water for 180 days. Sperm count, histology in testes, oxidative stress biomarkers, cell cycle progress and apoptosis were assessed...
September 29, 2018: Toxicology
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