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Archives of Toxicology

Nuno Guerreiro Oliveira, Ricardo Jorge Dinis-Oliveira
Cocaine is one of the most widely consumed psychoactive substances and has been recognized as a major public health concern for many years. While several aspects of the toxicology of cocaine have been thoroughly described in the literature, namely its effects on different target organs, other toxicological features should not be disregarded. In this perspective, the in vitro and in vivo genotoxic effects of cocaine, along with the genotoxicity data from human exposure, especially in the context of "crack" smoking, were reviewed...
August 16, 2018: Archives of Toxicology
Fatemeh Yavari, Christoph van Thriel, Michael A Nitsche, Min-Fang Kuo
Toluene is a well-known neurotoxic organic solvent and a major component of many industrial and commercial products such as adhesives, paint thinners and gasoline. Many workers are regularly exposed to toluene in their working environment and occupational exposure limits (OELs) have been set to avoid adverse health effects. These OELs or short-term exposure limits vary from 14 to 300 ppm across countries partly due to heterogeneity of the findings from animal and human studies about its neurotoxic effects and the evaluation of the adversity of the underlying mechanisms...
August 10, 2018: Archives of Toxicology
Le Tao, Dongying Xue, Dongxiao Shen, Wenting Ma, Jie Zhang, Xuefei Wang, Wei Zhang, Liu Wu, Kai Pan, Yanqin Yang, Zeribe C Nwosu, Steven Dooley, Ekihiro Seki, Cheng Liu
MicroRNA (miRNA)-mediated gene regulation contributes to liver pathophysiology, including hepatic stellate cell (HSC) activation and fibrosis progression. Here, we investigated the role of miR-942 in human liver fibrosis. The expression of miR-942, HSC activation markers, transforming growth factor-beta pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI), as well as collagen deposition, were investigated in 100 liver specimens from patients with varying degree of hepatitis B virus (HBV)-related fibrosis...
August 10, 2018: Archives of Toxicology
Emanuela Corsini, Ayşe Başak Engin, Monica Neagu, Valentina Galbiati, Dragana Nikitovic, George Tzanakakis, Aristidis M Tsatsakis
Chemical allergens are small molecules able to form a sensitizing complex once they bound to proteins. One of the most frequent manifestations of chemical allergy is contact hypersensitivity, which can have serious impact on quality of life. Allergic contact dermatitis is a predominantly CD8 + T cell-mediated immune disease, resulting in erythema and eczema. Chemical allergy is of considerable importance to the toxicologist, who has the responsibility of identifying and characterizing the allergenic potential of chemicals, and estimating the risk they pose to human health...
August 10, 2018: Archives of Toxicology
Anne-Marie Saillenfait, Sophie Ndaw, Alain Robert, Jean-Philippe Sabaté
Organophosphate triesters (PEFRs) are used increasingly as flame retardants and plasticizers in a variety of applications, such as building materials, textiles, and electric and electronic equipment. They have been proposed as alternatives to brominated flame retardants. This updated review shows that biomonitoring has gained incrementally greater importance in evaluating human exposure to PEFRs, and it holds the advantage of taking into account the multiple potential sources and various intake pathways of PEFRs...
August 10, 2018: Archives of Toxicology
Anja Ekdahl, Lars Weidolf, Matthew Baginski, Yoshio Morikawa, Richard A Thompson, Ian D Wilson
The metabolic fate of the human hepatotoxin fenclozic acid ([2-(4-chlorophenyl)-1,3-thiazol-4-yl]acetic acid) (Myalex) was studied in normal and bile-cannulated chimeric mice with a humanized liver, following oral administration of 10 mg/kg. This in vivo animal model was investigated to assess its utility to study "human" metabolism of fenclozic acid, and in particular to explore the formation of electrophilic reactive metabolites (RMs), potentially unique to humans. Metabolism was extensive, particularly involving the carboxylic acid-containing side chain...
August 9, 2018: Archives of Toxicology
Heidi E Schwartz-Zimmermann, Christian Hametner, Veronika Nagl, Iris Fiby, Lukas Macheiner, Janine Winkler, Sven Dänicke, Erica Clark, James J Pestka, Franz Berthiller
The original article can be found online.
August 7, 2018: Archives of Toxicology
Lea Wagmann, Hans H Maurer, Markus R Meyer
Transporter-mediated drug-drug interactions (DDI) may induce adverse clinical events. As drugs of abuse (DOA) are marketed without preclinical safety studies, only very limited information about interplay with membrane transporters are available. Therefore, 13 DOA of various classes were tested for their in vitro affinity to the human breast cancer resistance protein (hBCRP), an important efflux transporter. As adenosine 5'-triphosphate (ATP) hydrolysis is crucial for hBCRP activity, adenosine 5'-diphosphate (ADP) formation was measured and used as in vitro marker for hBCRP ATPase activity...
August 6, 2018: Archives of Toxicology
Anamaria Brozovic
No abstract text is available yet for this article.
July 23, 2018: Archives of Toxicology
Selahaddin Sezgin, Reham Hassan, Sebastian Zühlke, Lars Kuepfer, Jan G Hengstler, Michael Spiteller, Ahmed Ghallab
Acetaminophen (APAP) is one of the most intensively studied compounds that causes hepatotoxicity in the pericentral region of the liver lobules. However, spatio-temporal information on the distribution of APAP, its metabolites and GSH adducts in the liver tissue is not yet available. Here, we addressed the question, whether APAP-GSH adducts and GSH depletion show a zonated pattern and whether the distribution of APAP and its glucuronide as well as sulfate conjugates in liver lobules are zonated. For this purpose, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) technique was established, where the MSI images were superimposed onto CYP2E1 immunostained tissue...
July 23, 2018: Archives of Toxicology
Stephanie Kim, Amy Li, Stefano Monti, Jennifer J Schlezinger
Tributyltin (TBT), a peroxisome proliferator-activated receptor γ (PPARγ)/retinoid X receptor (RXR) ligand and founding member of the environmental obesogen chemical class, induces adipocyte differentiation and suppresses bone formation. A growing number of environmental PPARγ ligands are being identified. However, the potential for environmental PPARγ ligands to induce adverse metabolic effects has been questioned because PPARγ is a therapeutic target in treatment of type II diabetes. We evaluated the molecular consequences of TBT exposure during bone marrow multipotent mesenchymal stromal cell (BM-MSC) differentiation in comparison to rosiglitazone, a therapeutic PPARγ ligand, and LG100268, a synthetic RXR ligand...
July 19, 2018: Archives of Toxicology
Christine Höllerer, Günther Becker, Thomas Göen, Elisabeth Eckert
Tri-(2-ethylhexyl) trimellitate (TEHTM) is a plasticizer for PVC material and is used for medical devices as an alternative to di-(2-ethylhexyl) phthalate. As plasticizers are known to migrate easily into contact liquids, exposure of patients to TEHTM is highly probable. In the present study, human metabolism pathways of TEHTM and its elimination kinetics were investigated. For that purpose, four healthy volunteers were orally exposed to a single dose of TEHTM. TEHTM and its postulated primary metabolites were investigated in blood samples (up to 48 h after exposure), and in urine samples (collected until 72 h after exposure) using liquid chromatography tandem mass spectrometry (LC-MS/MS)...
July 19, 2018: Archives of Toxicology
Yan Xin, Bin Wan, Yu Yang, Xue-Jing Cui, Yi-Chun Xie, Liang-Hong Guo
Wide application of perfluoroalkyl acids (PFAAs) has raised great concerns on their side-effects on human health. PFAAs have been shown to accumulate mainly in the liver and cause hepatotoxicity. However, PFAAs can also deposit in lung tissues through air-borne particles and cause serious pulmonary toxicity. But the underlying mechanisms are still largely unknown. Autophagy is a type of programmed cell death parallel to necrosis and apoptosis, and may be involved in the lung toxicity of PFAAs. In this study, lung cancer cells, A549, were employed as the model to investigate the effects of three PFAAs with different carbon chain lengths on cell autophagy...
July 18, 2018: Archives of Toxicology
Yaochen Zhang, Don-Kyu Kim, Yoon Seok Jung, Yong-Hoon Kim, Yong Soo Lee, Jina Kim, Won-Il Jeong, In-Kyu Lee, Sung Jin Cho, Steven Dooley, Chul-Ho Lee, Hueng-Sik Choi
Upon liver intoxication with malnutrition or high-fat diet feeding, fibrinogen is synthesized by hepatocytes and secreted into the blood in human and mouse. Its primary function is to occlude blood vessels upon damage and thereby stop excessive bleeding. High fibrinogen levels may contribute to the development of pathological thrombosis, which is one mechanism linking fatty liver disease with cardiovascular disease. Our previous results present ERRγ as key regulator of hepatocytic fibrinogen gene expression in human...
July 17, 2018: Archives of Toxicology
Shupeng Yang, Huiyan Zhang, Jinzhen Zhang, Yanshen Li, Yue Jin, Suxia Zhang, Sarah De Saeger, Yi Li, Jinhui Zhou, Feifei Sun, Marthe De Boevre
Zearalenone-14-glucoside (ZEN-14G), the modified mycotoxin of zearalenone (ZEN), has attracted considerable attention due to its high potential to be hydrolyzed into ZEN, which would exert toxicity. It has been confirmed that the microflora could metabolize ZEN-14G to ZEN. However, the metabolic profile of ZEN-14G and whether it could be deglucosidated in the liver are unknown. To thoroughly investigate the metabolism of ZEN-14G, in vitro metabolism including phase I and phase II metabolism was studied using liquid chromatography coupled to high-resolution mass spectrometry...
July 17, 2018: Archives of Toxicology
Masaki Takeuchi, Shingo Oda, Koichi Tsuneyama, Tsuyoshi Yokoi
Sinusoidal obstruction syndrome (SOS) is a liver injury caused by clinical chemotherapy, of which pathogenesis is associated with the damage in liver sinusoidal endothelial cells (LSEC). The unavailability of appropriate specific biomarkers for the early diagnosis of SOS may potentially overlook SOS patients. In this study, we sought to find serum microRNAs (miRNAs) as non-invasive biomarkers for investigating SOS in rats. Male Sprague-Dawley rats were orally administered monocrotaline, and then, their livers and sera were collected after 0...
July 17, 2018: Archives of Toxicology
Nobumitsu Hanioka, Susumu Ohkawara, Takashi Isobe, Sadayuki Ochi, Toshiko Tanaka-Kagawa, Hideto Jinno
Daidzein, one of the major soy isoflavones, has a number of beneficial bioactivities for human health. It is mainly metabolized into 7- and/or 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in mammals, including humans. The present study was conducted to examine the regioselective glucuronidation of daidzein at the 7- and 4'-hydroxyl groups in the liver and intestinal microsomes of humans, monkeys, rats, and mice. Daidzein glucuronidation activities at substrate concentrations of 1.0-200 µM were assessed, and Eadie-Hofstee plots were constructed...
July 16, 2018: Archives of Toxicology
Hee Young Kwon, Ju-Ha Kim, Bonglee Kim, Sanjay K Srivastava, Sung-Hoon Kim
This article contains an error.
July 16, 2018: Archives of Toxicology
Yi-Wen Li, Chung-Hsing Wang, Chao-Jung Chen, Charles C N Wang, Cheng-Li Lin, Wai-Kok Cheng, Hsin-Yi Shen, Yun-Ping Lim
To characterize the association between epilepsy, use of antiepileptic drugs (AEDs), and the risk of hyperlipidemia, we conducted a nationwide population-based cohort study with data obtained from the National Health Insurance Research Database of Taiwan. The effects of AEDs on lipogenic gene expression were also examined in vitro. We identified 3617 cases involving patients, whose epilepsy was newly diagnosed between 2000 and 2011, and selected a comparison cohort comprising 14,468 patients without epilepsy...
July 13, 2018: Archives of Toxicology
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