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Toxicology Letters

M Teresa Donato, Mireia López-Riera, José V Castell, María J Gómez-Lechón, Ramiro Jover
Disruption of the vectorial bile acid transport in the liver is a key feature of cholestatic drugs, although many causal and mechanistic aspects are still unknown. The aim of the present study was to explore if cholestatic drugs can repress or induce the expression of hepatic transporters. To this end, sandwich-cultured rat hepatocytes were treated with cholestatic and non-cholestatic (steatotic, non-hepatotoxic, etc.) drugs and the mRNA expression of 10 uptake and efflux biliary transporters was measured. Results evidenced that all cholestatic drugs cause extensive alterations in the mRNA expression of most biliary transporters...
October 17, 2016: Toxicology Letters
M L V Azevedo, N B Bonan, G Dias, F Brehm, T M Steiner, W M Souza, A E M Stinghen, F C Barreto, Selene Elifio-Esposito, R Pecoits-Filho, A N Moreno-Amaral
Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×10(6) cells/mL) were incubated with pCS (10, 25, or 50μg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12...
October 16, 2016: Toxicology Letters
Martina Štěpánková, Kristýna Krasulová, Aneta Dořičáková, Ondřej Kurka, Pavel Anzenbacher, Zdeněk Dvořák
Dihydropyridine calcium channel blockers (CCBs) are used as anti-hypertensives and in the treatment of angina pectoris. Structurally, CCBs have at least one chiral center in the molecule, thereby existing in two or more different enantiomers. In the current paper we examined effects of benidipine, felodipine and isradipine enantiomers on the expression and enzyme activities of human xenobiotics-metabolizing cytochromes P450. All CCBs dose-dependently activated aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), as revealed by gene reporter assays...
October 9, 2016: Toxicology Letters
Jie Liu, Yuan-Fu Lu, Wen-Kai Li, Zheng-Ping Zhou, Ying-Ying Li, Xi Yang, Cen Li, Yu-Zhi Du, Li-Xin Wei
Mercury sulfides (α-HgS, β-HgS) are frequently included in traditional medicines. Mercury is known for nephrotoxicity, their safety is of concern. To address this question, mice were orally administrated with Zuotai (54% β-HgS, 30mg/kg), α-HgS (HgS, 30mg/kg), HgCl2 (33.6mg/kg), or MeHgCl (3.1mg/kg) for 7 days, and nephrotoxicity was examined. Animal body weights were decreased by HgCl2 and to a lesser extent by MeHg, but unaltered after Zuotai and HgS. HgCl2 and MeHg produced renal tubular vacuolation, interstitial inflammation and cell degeneration with protein cysts in the tubular lumen, while these pathological lesions were mild in Zuotai and HgS-treated mice...
October 6, 2016: Toxicology Letters
Ruijuan Guan, Xiaomei Zhao, Xia Wang, Nana Song, Yuhong Guo, Xianxia Yan, Liping Jiang, Wenjing Cheng, Linlin Shen
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the underlying mechanism remains largely unknown. This study aimed to further investigate the effects of emodin on the inflammation and fibrosis of BLM-induced pulmonary fibrosis and the mechanism involved in rats. Our results showed that emodin improved pulmonary function, reduced weight loss and prevented death in BLM-treated rats...
October 4, 2016: Toxicology Letters
Ryo Mitsugi, Tomoo Itoh, Ryoichi Fujiwara
Trovafloxacin develops severe hepatotoxicity; however, the underlying mechanism of the trovafloxacin-induced liver injury has not been cleared. It has been shown that microRNAs (miRNAs) can be involved in the development of drug-induced liver injuries. We performed a miRNA microarray analysis to identify hepatic miRNAs that were induced or reduced by trovafloxacin in mice. It was demonstrated that miR-877-5p was the most increased miRNA in the mouse liver 24hours after the trovafloxacin administration. To investigate the role of miR-877-5p in the liver, we established miR-877-5p-overexpressed HepG2 cells...
October 3, 2016: Toxicology Letters
Katy O Goyak, Ming H Kung, Min Chen, Keith K Aldous, James J Freeman
Residual aromatic extracts (RAE) are petroleum substances with variable composition predominantly containing aromatic hydrocarbons with carbon numbers greater than C25. Because of the high boiling nature of RAEs, the aromatics present are high molecular weight, with most above the range of carcinogenic polycyclic aromatic hydrocarbons (PAHs). However, refinery distillations are imperfect; some PAHs and their heteroatom-containing analogs (collectively referred to as polycyclic aromatic content or PAC) may remain in the parent stream and be extracted into the RAE, and overall PAC content is related to the carcinogenic potential of an RAE...
October 3, 2016: Toxicology Letters
Henriqueta Louro, Mariana Pinhão, Joana Santos, Ana Tavares, Nádia Vital, Maria João Silva
To contribute with scientific evidence to the grouping strategy for the safety assessment of multi-walled carbon nanotubes (MWCNTs), this work describes the investigation of the cytotoxic and genotoxic effects of four benchmark MWCNTs in relation to their physicochemical characteristics, using two types of human respiratory cells. The cytotoxic effects were analysed using the clonogenic assay and replication index determination. A 48h-exposure of cells revealed that NM-401 was the only cytotoxic MWCNT in both cell lines, but after 8-days exposure, the clonogenic assay in A549 cells showed cytotoxic effects for all the tested MWCNTs...
October 1, 2016: Toxicology Letters
Valentina Bušić, Maja Katalinić, Goran Šinko, Zrinka Kovarik, Dajana Gašo-Sokač
Organophosphorus (OP) nerve agents (sarin, tabun VX and soman) inhibit the enzyme acetylcholinesterase (AChE, EC by binding to its active site while preventing neurotransmission in the cholinergic synapses. The protection and treatment of this kind of poisoning are still a challenge as we are yet to discover an antidote that would be effective in all cases of poisoning. To aid the search for more efficient antidotes, we evaluated the ability of nine pyridoxal oxime derivatives, prepared by a novel synthetic pathway, to reactivate recombinant human AChE and the related purified human plasma butyrylcholinesterase (BChE, EC 3...
September 29, 2016: Toxicology Letters
Antonietta Stellavato, Monica Lamberti, Anna Virginia Adriana Pirozzi, Francesca de Novellis, Chiara Schiraldi
Myclobutanil is a conazole class fungicide widely used as an agrichemical. It is approved for use on fruit, vegetables and seed commodities in the EU and elsewhere to control fungi such as Ascomycetes, Fungi Imperfecti and, Basidiomycetes. Its widespread use has raised the issue of possible health risks for agrarian communities and the general population, which can be exposed to residues present in food and drinking water. The toxicities identified include adverse effects on liver and kidney and on the development of male reproductive organs...
September 28, 2016: Toxicology Letters
Yong Yang, Ting Bai, You-Li Yao, De-Quan Zhang, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
Thymoquinone (TQ) is a biologically active compound isolated from the seeds of Nigella sativa L. (Ranuculaceae). This study investigated the hepato-protective effect of TQ on liver injury through AMP-activated protein kinase (AMPK) signaling in hepatic stellate cells (HSCs). In vitro, TGF-β time-dependently attenuated liver kinase B-1 (LKB1) and AMPK phosphorylation, which were blocked by pretreatment with TQ and AICAR (an activator of AMPK). TQ significantly inhibited collagen-Ι, α-SMA, TIMP-1 and enhanced MMP-13 expression, contributing to prevent TGF-β-induced human HSCs activation...
September 26, 2016: Toxicology Letters
Yasukazu Takanezawa, Ryosuke Nakamura, Yuka Sone, Shimpei Uraguchi, Masako Kiyono
Methylmercury (MeHg) is a widespread environmental pollutant and causes a serious hazard to health worldwide. However, molecular mechanisms underlying MeHg toxicity remain elusive. We show that MeHg reduced mouse embryonic fibroblast (MEF) viability in a dose-dependent manner. Furthermore, MeHg treatment increased levels of autophagy markers LC3-II and p62, possibly by acting on the MAPKs signaling pathway in several cell types. MeHg exposure elevated the number of LC3 puncta in stable GFP-LC3 MEFs and the number of autophagic vacuoles...
September 22, 2016: Toxicology Letters
Juergen Pauluhn
To characterize the accumulated hazards associated with the inhalation of gases typical of combustion products, a time-integrated value known as the fractional effective dose (FED) is used. This FED is maintained by the International Organization for Standardization (ISO) and made publicly available as the Standard ISO 13571. The current FED calculation related to asphyxiant gases is based on non-human primate data to estimate the 50% probability of humans to be incapacitated or not being able to execute any escape paradigm from fires...
September 21, 2016: Toxicology Letters
Joost Smit, Mary-Lène de Zeeuw-Brouwer, Manon van Roest, Govardus de Jong, Jolanda van Bilsen
The current methodology to identify allergenic food proteins is effective in identifying those that are likely to cross-react with known allergens. However, most assays show false positive results for low/non-allergens. Therefore, an ex vivo/in vitro DC-T cell assay and an in vivo mouse model were used to distinguish known allergenic food proteins (Ara h 1, β-Lactoglobulin, Pan b 1, bovine serum albumin, whey protein isolate) from low/non allergenic food proteins (soy lipoxygenase, gelatin, beef tropomyosin, rubisco, Sola t 1)...
September 20, 2016: Toxicology Letters
Yasumitsu Takimoto, Takao Imai, Makoto Kondo, Yukiko Hanada, Atsuhiko Uno, Yusuke Ishida, Takefumi Kamakura, Tadashi Kitahara, Hidenori Inohara, Shoichi Shimada
Cisplatin is a chemotherapeutic agent commonly used for the treatment of solid tumors, and its side-effects include vestibulotoxicity. Previous studies have reported cisplatin-induced vestibulotoxicity in various animal models, but no study has investigated in vivo mouse vestibular dysfunction after cisplatin. The aim of this study was to investigate cisplatin-induced vestibulotoxicity in C57BL/6J mice. Vestibular function was assessed by recording the vestibulo-ocular reflex (VOR). This was done during sinusoidal rotations in the horizontal plane at three frequencies (0...
September 19, 2016: Toxicology Letters
Sean D Kodani, Haley B Overby, Christophe Morisseau, Jiangang Chen, Ling Zhao, Bruce D Hammock
Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics...
September 19, 2016: Toxicology Letters
Huan Xu, Shea McClain, Sebastian Medina, Fredine T Lauer, Christelle Douillet, Ke Jian Liu, Laurie G Hudson, Miroslav Stýblo, Scott W Burchiel
It is known in humans and mouse models, that drinking water exposures to arsenite (As(+3)) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As(+3), and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb As(+3)via drinking water for 30d...
September 19, 2016: Toxicology Letters
Qiu-Yue Yi, Hong-Bao Li, Jie Qi, Xiao-Jing Yu, Chan-Juan Huo, Xiang Li, Juan Bai, Hong-Li Gao, Bo Kou, Kai-Li Liu, Dong-Dong Zhang, Wen-Sheng Chen, Wei Cui, Guo-Qing Zhu, Xiao-Lian Shi, Yu-Ming Kang
Reactive oxygen species (ROS) in the brain are involved in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG), one of the active compounds in green tea, has anti-oxidant, anti-inflammatory and vascular protective properties. This study was designed to determine whether chronic infusion of EGCG into the hypothalamic paraventricular nucleus (PVN) attenuates ROS and sympathetic activity and delays the progression of hypertension by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and decreasing nuclear factor-kappa B (NF-κB) activity, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR)...
September 19, 2016: Toxicology Letters
Franz Worek, Thomas Seeger, Katharina Neumaier, Timo Wille, Horst Thiermann
The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals...
September 14, 2016: Toxicology Letters
Linling Que, Liu He, Chenshu Yu, Wencheng Yin, Liwen Ma, Baoshan Cao, Siwang Yu
Myelosuppression is the most common dose-limiting adverse effect of chemotherapies. In the present study, we investigated the involvement of nuclear erythroid 2-related factor 2 (Nrf2) in cyclophosphamide-induced myelosuppression in mice, and evaluated the potential of activating Nrf2 signaling as a preventive strategy. The whole blood from Nrf2(-/-) mice exhibited decreased antioxidant capacities, while the bone marrow cells, peripheral blood mononuclear cells and granulocytes from Nrf2(-/-) mice were more susceptible to acrolein-induced cytotoxicity than those from wild type mice...
September 12, 2016: Toxicology Letters
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