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Franziska Paech, Vanessa F Abegg, Urs Duthaler, Luigi Terracciano, Jamal Bouitbir, Stephan Krähenbühl
Reports concerning hepatic mitochondrial toxicity of sunitinib are conflicting. We therefore decided to conduct a toxicological study in mice. After having determined the highest dose that did not affect nutrient ingestion and body weight, we treated mice orally with sunitinib (7.5 mg/kg/day) for 2 weeks. At the end of treatment, peak sunitinib plasma concentrations were comparable to those achieved in humans and liver concentrations were approximately 25-fold higher than in plasma. Sunitinib did not affect body weight, but increased plasma ALT activity 6-fold...
July 18, 2018: Toxicology
Mónica Elizabeth Mosquera Ortega, Delfina Mercedes Romero, Alejandro Martín Pato, Carla Solange Sosa-Holt, Adriana Ridolfi, Edda Villaamil Lepori, Marcelo Javier Wolansky
Pyrethroids (PYRs) are synthetic insecticides increasingly used in agricultural and household pest control. Little is known on how the toxicity of highly effective bolus doses of single compounds compares to more realistic scenarios of low-level exposure to PYR mixtures. In this study, we examined a quaternary mixture of two noncyano (tefluthrin, TEF; bifenthrin, BIF) and two cyano (α-cypermethrin, α-CPM; deltamethrin, DTM) PYRs in young adult rats. These compounds are mostly composed of PYR isomers ranking top ten in acute lethality in rats...
July 12, 2018: Toxicology
Jiri Kassa, Christopher M Timperley, Mike Bird, Rebecca L William, A Christopher Green, John E H Tattersall
The effect of three newly developed bispyridinium non-oxime compounds (MB408, MB442, and MB444) on the therapeutic efficacy of a standard antidotal treatment (atropine in combination with the oxime HI-6 or obidoxime) of acute poisoning by two nerve agents (sarin and cyclosarin) in mice was studied. The therapeutic efficacy of atropine in combination with an oxime with or without one of the bispyridinium non-oximes was evaluated by determination of the 24 h LD50 values of the nerve agents studied and by measurement of the survival time after supralethal poisoning...
July 10, 2018: Toxicology
Ana Priscila Gomes Silva, Marcella da Silva Araujo Santiago, Luciane Alves Maranho, Rodolpho Pereira de Oliveira, Dulce Helena Jardim Constantino, Camilo Dias Seabra Pereira, Regina Cláudia Barbosa da Silva, Juliana Elaine Perobelli
Manganese (Mn) is one of the most common chemical elements on Earth and an essential micronutrient in animal organism. However, in supraphysiological levels and long-term exposures, it is a potential toxicant. Although nervous system is the most studied in relation to Mn toxicity, other tissues can have their function impaired by Mn in high doses. The present study investigated the possible adverse effects of subchronic exposure to supraphysiologic level of Mn (5 mg/Kg or 15 mg/Kg, intraperitoneally) on reproductive, neurobehavioral, renal and hepatic parameters of male rats...
July 7, 2018: Toxicology
Guihua Wang, Bo He, Wen Hu, Kexin Liu, Xiaohan Gong, Hao Kou, Yu Guo, Hui Wang
Anti-thyroid drugs (ATDs) therapy is necessary for pregnant women with hyperthyroidism. However, there is a lack of studies on developmental toxicity of ATDs. In this study, we observed the developmental toxicity of fetal liver induced by prenatal methimazole exposure (PME) in mice, and explored the potential mechanism. Pregnant Kunming mice were administered intragastrically with 4.5 or 18 mg/kg·d methimazole from gestational day (GD) 9~18. After PME, the birth weights of the offspring mice were decreased, and the liver morphology, development indexes and metabolic function were all altered in different degree in the PME fetuses...
July 7, 2018: Toxicology
Hui Ye, Samantha Z Dudley, Ian C Shaw
How does estrogen receptor-α bind its natural ligands - estrogens? How can other molecules mimic estrogens and elicit different estrogenic responses? The answers lie in a complex and intimate chemical biology between ligands and receptor. This delicate interaction at the ligand binding cleft signals, via conformational change, exposure of a specific new charge topography at a second site (Activation Function-2). This, in turn, attracts a regulatory protein which modulates gene expression and controls biological activity...
July 6, 2018: Toxicology
Qiaozhu Tan, Zhitao Liu, Hong Li, Yongjun Liu, Zhenghua Xia, Yuancan Xiao, Muhammad Usman, Yuzhi Du, Hongtao Bi, Lixin Wei
Mercury chloride (HgCl2 ), a neurotoxicant that cannot penetrate the blood-brain barrier (BBB). Although when the BBB are got damaged by neurodegenerative disorders, the absorbed HgCl2 , mainly in form of Hg (II)-serum albumin adduct (Hg-HSA) in human plasma, can penetrate BBB and affect central nervous system (CNS) cells. Current study planned to evaluate the effect of Hg-HSA on the physiological function of N9 microglial cells. At low dosage (15 ng/mL) of Hg-HAS, the observed outcomes was: promoted cell propagation, Nitric Oxide (NO) and intracellular Ca2+ levels enhancement, suppressed the release of TNF-α and IL-1β and inhibited cell proliferation...
July 5, 2018: Toxicology
Huaisha Xu, Xiaodong Chen, Jun Wang, Tingyu Yang, Na Liu, Jie Cheng, Rong Gao, Jingli Liu, Hang Xiao
Methamphetamine (METH), an amphetamine-like drug, is one of the most commonly used central nervous system psychostimulants worldwide. METH abuse frequently leads to cognitive decline and dementia-like changes, but the mechanisms remain poorly understood. In the present study, the mechanisms of METH-induced changes in Alzheimer's disease-like pathological protein in Neuro2 A cells were explored. Our results indicated that METH exposure significantly increased the expression of the pathological protein hyperphosphorylated tau (p-tau)...
July 4, 2018: Toxicology
Tamalika Sanyal, Pritha Bhattacharjee, Sandip Bhattacharjee, Pritha Bhattacharjee
Groundwater arsenic contamination has become a serious global concern due to its adverse effects on human health. Arsenic-induced reactive oxygen species trigger oxidative stress inside mitochondria, which initiate a cascade of events including altered mitochondrial (mt) membrane potential, uncoupling of electron transport chain, and mtDNA damage. A case-control study was conducted to examine the association between arsenic exposure and differences in mtDNA methylation and to assess the downstream consequences...
June 22, 2018: Toxicology
Chia-Yen Wu, Yi-Lin Tsai, Chung-Pin Hsieh, Tsui Chin Wang, Ming-Huan Chan, Hwei-Hsien Chen
Toluene, a commonly used organic solvent, produces a variety of behavioral disturbances in both humans and animals comparable to noncompetitive N-methyl-D-aspartate receptor (NMDARs) antagonists, such as phencyclidine (PCP). N-acetylcysteine (NAC) is capable of reversing the psychotomimetic effects of PCP via activation of cystine-glutamate antiporters (xCT). The present study examined whether NAC is capable of attenuating the toluene-induced brain stimulation reward enhancement and behavioral manifestations...
June 21, 2018: Toxicology
Cintia Scucuglia Heluany, Leonard de Vinci Kanda Kupa, Mariana Nascimento Viana, Cristina Maria Fernandes, Eduardo Lani Volpe Silveira, Sandra Helena Poliselli Farsky
Robust correlation between the severity of rheumatoid arthritis (RA) and cigarette smoking has been clinically demonstrated. Nevertheless, cigarette compounds responsible for this toxic effect and their mechanisms have not been described. Considering that hydroquinone (HQ) is an abundant, pro-oxidative compound of the matter particle phase of cigarette smoke, we investigated whether HQ exposure during the initial phase of collagen-induced arthritis (CIA) could aggravate the disease. For this purpose, male Wistar rats were exposed to aerosolized HQ (25 ppm), saline or 5% ethanol solution (HQ vehicle) for 1 h per day during 14 days...
June 21, 2018: Toxicology
Beata Dąbrowska-Bouta, Grzegorz Sulkowski, Małgorzata Frontczak-Baniewicz, Joanna Skalska, Mikołaj Sałek, Jolanta Orzelska-Górka, Lidia Strużyńska
The widespread use of silver nanoparticles (AgNPs) in medicine and in multiple commercial products has motivated researchers to investigate their potentially hazardous effects in organisms. Since AgNPs may easily enter the brain through the blood-brain barrier (BBB), characterization of their interactions with cellular components of the neurovascular unit (NVU) is of particular importance. Therefore, in an animal model of prolonged low-dose exposure, we investigate the extent and mechanisms of influence of AgNPs on cerebral microvessels...
June 20, 2018: Toxicology
Theodore A Slotkin, Ashley Ko, Frederic J Seidler
Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth...
June 20, 2018: Toxicology
Guillemette Crépeaux, Romain K Gherardi
No abstract text is available yet for this article.
June 14, 2018: Toxicology
Zhijun Wu, Juan Cheng, Xuejun Guo, Chunguang Ding, Xin Jin, Qidong Ren, Min Zheng, Lei Wang, Wenjin Zhao
Toxicity of antimony (Sb) to humans may occur through environmental, occupational, and therapeutic exposures. The underlying mechanism of its accumulation in red blood cells (RBCs) is not clear. Here, the processes and mechanism of RBCs sequestering Sb were explored through a series of in vitro and in vivo studies. These include binding affinity of Sb compounds with rat hemoglobin (Hb) and RBCs, acute exposure of antimony potassium tartrate (APTIII ), and subchronic oral exposure of APTIII , potassium pyroantimonate (PPV ) and antimony trioxide (ATIII )...
June 13, 2018: Toxicology
Min Liu, Biao Chen, Linguo Pei, Qi Zhang, Yunfei Zou, Hao Xiao, Jin Zhou, Liaobin Chen, Hui Wang
Prenatal dexamethasone exposure (PDE) could induce testicular developmental toxicity in adults. The present study aims to confirm its intrauterine origination, and to explore its potential intrauterine programming mechanism. The pregnant rats were respectively injected subcutaneously with 0.2 and 0.8 mg/kg d dexamethasone during gestational days (GD) 9 to 20. The testes and serum of offspring rats were collected on GD20 and postnatal week (PW) 12. In vivo, PDE significantly induced the abnormal testicular morphology in offspring from GD20 to PW12...
June 11, 2018: Toxicology
Sean X Naughton, Caterina M Hernandez, Wayne D Beck, Indrani Poddar, Nathan Yanasak, Ping-Chang Lin, Alvin V Terry
Organophosphates (OPs) are found in hundreds of valuable agricultural, industrial, and commercial compounds; however, they have also been associated with a variety of harmful effects in humans. The acute toxicity of OPs is attributed to the inhibition of the enzyme acetylcholinesterase (AChE); however, this mechanism may not account for all of the deleterious neurologic effects of OPs, especially at doses that produce no overt signs of acute toxicity. In this study, the effects of two weeks of daily subcutaneous exposure to the OP-nerve agent diisopropylfluorophosphate (DFP) in doses ranging from 0...
June 9, 2018: Toxicology
Natalia Fernández-Bertólez, Carla Costa, Fátima Brandão, Gözde Kiliç, Joao Paulo Teixeira, Eduardo Pásaro, Blanca Laffon, Vanessa Valdiglesias
Iron oxide nanoparticles (ION) awaken a particular interest for biomedical applications due to their unique physicochemical properties, especially superparamagnetism, and ability to cross the blood-brain barrier. ION surface can be coated to improve their properties and facilitate functionalization. Still, coating may affect toxicity. The aim of this work was to evaluate the possible effects of oleic acid-coated ION (O-ION) on human neuronal cells (SH-SY5Y). A set of assays was conducted in complete and serum-free culture media for 3 and 24 h to assess O-ION cytotoxic effects - cell membrane disruption, cell cycle alteration and cell death induction -, and genotoxic effects - primary DNA damage, H2AX phosphorylation and micronuclei induction -, considering also DNA repair competence and iron ion release...
June 6, 2018: Toxicology
Wei Liu, Chao Xu, Di Ran, Yi Wang, Hongyan Zhao, Jianhong Gu, Xuezhong Liu, Jianchun Bian, Yan Yuan, Zongping Liu
Ca2+ is an important ion in various intracellular metabolic pathways. Endoplasmic reticulum (ER) is a major intracellular calcium store and ER calcium homeostasis plays a key part in the regulation of apoptosis. We have previously shown that Cadmium (Cd) induces apoptosis in osteoblasts (OBs), accompany by increased cytoplasmic calcium. As the role of calcium in OBs apoptosis induced by Cd has not been clarified we investigated the effects of Cd exposure in rat OBs on intracellular Ca2+ , CaMKII phosphorylation, and the pathways implicated in inducing apoptosis...
June 5, 2018: Toxicology
Guoren Huang, Jinli Xue, Xiangjun Sun, Jing Wang, Liangli Lucy Yu
Fatty acid esters of 3-chloro-1, 2-propanediol (3-MCPD) are a group of processing-induced food contaminants with nephrotoxicity. This study investigated whether and how necroptosis played a role in the nephrotoxic effect of 3-MCPD-dipalmitate (2.5 g/kg BW) in C57 BL/6 mice. The results showed that the principal components in necroptosis pathway including receptor-interacting protein 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) were up-regulated in 3-MCPD-dipalmitate-induced acute kidney injury (AKI)...
May 31, 2018: Toxicology
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