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Chemical Research in Toxicology

Francesca Cavaliere, Pietro Cozzini
Ever growing numbers of chemicals in food and drinking water make it impossible to address safety by classical approaches in toxicology. In silico chemical methods could be a first-line for hazard characterization, requiring food toxicology to expand the use of approaches currently well applied in medicinal chemistry.
September 19, 2018: Chemical Research in Toxicology
Yan Lou, Qian Wang, Jin Qi Zheng, Xi Wang, Wei Qin Jiang, Yi Zheng, Qing Wei Zhao, Yun Qing Qiu, Su Zeng
Hand-foot syndrome (HFS), the most common side effect of capecitabine, is a dose-limiting cutaneous toxicity with only rare therapeutic options. The causative mechanisms of HFS are still unclear. Many studies suggested that capecitabine or its metabolites caused the toxicity. This study is attempting to determine if there are any new metabolites that may be present and be linked to toxicity. For this purpose, 25 patients who ingested capecitabine orally were enrolled and divided into HFS positive and negative groups...
September 19, 2018: Chemical Research in Toxicology
Rosana Schafer, Ted J Ognibene, Michael A Malfatti, Kenneth W Turteltaub, John B Barnett
We have documented that the herbicide propanil, is immunotoxic in mice and our in vitro tissue culture experiments largely recapitulate the in vivo studies. Laboratory studies on environmental contaminants are the most meaningful when these studies are conducted using concentrations that approximate levels in the environment. Many techniques to measure the distribution and pharmacokinetics (PK) on compounds rely on techniques, such as liquid scintillation counting (LSC) of radio-labeled starting compound require concentrations higher than environmental levels...
September 19, 2018: Chemical Research in Toxicology
Nitika Singh, Abhishek Kumar, Vivek Kumar Gupta, Bechan Sharma
The effects of lead exposure on mammals are reported to be devastating. Lead is present in all the abiotic environmental components such as brass, dust, plumbing fixtures, soil, water, and lead mixed imported products. Its continuous use for several industrial and domestic purposes has caused a rise in its levels, thereby posing serious threats to human health. The mechanisms involved in lead-induced toxicity primarily include free-radical-mediated generation of oxidative stress which directly imbalances the prooxidants and the antioxidants in body...
September 17, 2018: Chemical Research in Toxicology
Gunnar Boysen
Wang and Giese point out an important mistake in the labeling of a figure 3 of our paper regarding cisplatin 1,2 intrastrand guanine-guanine adduct.1 They correctly noticed that the m/z 513.1 ion is in fact the CP-d(GpG) adduct minus the ribose phosphate back bone (d(RpR)) and minus one amino group [M-d(RpR)-NH2] and that the m/z 497.1 ion is the adduct minus the d(RpR) and minus two amino groups [M-d(RpR)-2(NH¬2)]. In addition, Wang and Giese suggest adding ions with m/z 530 and m/z 724 to the figure and description...
September 14, 2018: Chemical Research in Toxicology
Dongping Liao, Qiqi Wang, Jiali He, David B Alexander, Mohamed Abdelgied, Ahmed M El-Gazzar, Mitsuru Futakuchi, Masumi Suzui, Jun Kanno, Akihiko Hirose, Jiegou Xu, Hiroyuki Tsuda
Translocation of multiwalled carbon nanotubes (MWCNTs) from the lung to the pleural cavity, deposition of the fibers in the pleural tissue, induction of pleural fibrosis, and mesothelial proliferation have been found in rodents administered MWCNTs by different pulmonary exposure methods. However, whether the translocation and deposition and the subsequent pleural inflammation are associated with the pleural lesions is unclear. In the present study, male F344 rats were given 250 μg of two types of MWCNTs, with crocidolite as a positive control, 2 times/week for 4 weeks by intratracheal spraying...
September 13, 2018: Chemical Research in Toxicology
Toru Usui, Arun Tailor, Lee Faulkner, Xiaoli Meng, John Farrell, Ann K Daly, Gordon J Dear, B Kevin Park, Dean J Naisbitt
The HLA class I allele HLA-A*33:03 is a risk factor for ticlopidine-induced liver injury. Herein, we show HLA class I-restricted ticlopidine-specific CD8+ T-cell activation in healthy donors expressing HLA-A*33:03. Cloned CD8+ T-cells proliferated and secreted IFN-γ in the presence of ticlopidine and autologous antigen presenting cells. A reduction of the T-cell response after blocking with HLA-class I and HLA-A*33 antibodies indicates that the interaction between drugs and the HLA allele detected in genetic association studies may be important for T-cell activation...
September 13, 2018: Chemical Research in Toxicology
Yasuhiro Uno, Norie Murayama, Masami Kato, Saki Tanaka, Tomoko Ohkoshi, Hiroshi Yamazaki
Glutathione S-transferase (GST) is a family of important drug-metabolizing enzymes, conjugating endogenous and exogenous compounds. Genetic polymorphisms result in the inter-individual variability of GST activity in humans. Especially, human GSTT1 and GSTT2 null alleles are associated with toxicity and various cancers derived from chemicals. Cynomolgus macaque, a nonhuman primate species widely used in drug metabolism studies, has molecular and enzymatic similarities of GSTs to the human orthologs; however, genetic polymorphisms have not been investigated in this species...
September 13, 2018: Chemical Research in Toxicology
Astrid Barkleit, Christoph Hennig, Atsushi Ikeda-Ohno
Due to its chemo- and radiotoxicity, the incorporation of uranium into human body via ingestion potentially poses a serious health risk. When ingested, the gastrointestinal fluids are the primary media to interact with uranium, eventually influencing and even determining its biochemical behavior in the gastrointestinal tract and thereafter. The chemical interactions between uranium and the components of gastrointestinal fluids are, however, poorly understood to date. In this study, the complexation of uranium(VI) (as the uranyl ion, UO2 2+ ) with the protein α-amylase, one of the major enzymes in saliva and pancreatic juices, was investigated over a wide range of pH or uranium/ α-amylase concentrations covering physiological conditions...
September 12, 2018: Chemical Research in Toxicology
Naihao Lu, Yinhua Sui, Rong Tian, Yiyuan Peng
Proteins in the bloodstream bind to carbon nanotubes (CNTs) through noncovalent interactions to form a protein corona, thereby effectively influencing the biological properties and blood biocompatibility of the CNTs. Here, we investigated the binding of common plasma proteins (i.e. human immunoglobulin G (IgG), human serum albumin (HSA) and fibrinogen (FG)) to carboxylated single-walled CNTs (SWCNTs), and evaluated the effects of these different protein coronas on cytotoxicity to endothelial cells and immune response to neutrophils in the bloodstream...
September 12, 2018: Chemical Research in Toxicology
Emanuela Felley-Bosco, Marion MacFarlane
Asbestos fibers are naturally occurring silicates that have been extensively used in the past, including house construction, but because of their toxicity, their use has been banned in 63 countries. Despite this, more than one million metric tons of asbestos are still consumed annually in countries where asbestos use has not been banned. Asbestos-related disease incidence is still increasing in several countries, including those countries that banned the use of asbestos more than 30 years ago. We highlight here recent knowledge obtained in experimental models about the mechanisms leading to tumor development following asbestos exposure, including genetic and epigenetic changes...
September 12, 2018: Chemical Research in Toxicology
Li-Long Jiang, Yan Jiang, Dong-Sheng Zhao, Ya-Xi Fan, Qiong Yu, Ping Li, Hui-Jun Li
Emodin, a widely existing natural product in herbal medicines, has been reported to be hepatotoxic, but the exact underlying mechanism is still not fully understood. The objective of the present study was to evaluate the role of CYP3A and glutathione (GSH) in emodin-induced liver injury. Primary human hepatocytes were exposed to emodin with and without addition of CYP3A inducer/inhibitor and GSH synthesis inhibitor. It was found that emodin-mediated cytotoxicity increased when CYP3A was activated and GSH was depleted...
September 11, 2018: Chemical Research in Toxicology
Tiffany M Scharadin, Michael A Malfatti, Kurt Haack, Kenneth W Turteltaub, Chong-Xian Pan, Paul T Henderson, Brian A Jonas
Acute myeloid leukemia (AML) is a rare yet deadly cancer of the blood and bone marrow. Presently, induction chemotherapy with the DNA damaging drugs cytarabine (ARA-C) and idarubicin (IDA), known as 7 + 3, is the standard of care for most AML patients. However, 7 + 3 is a relatively ineffective therapy, particularly in older patients, and has serious therapy-related toxicities. Therefore, a diagnostic test to predict which patients will respond to 7 + 3 is a critical unmet medical need. We hypothesize that a threshold level of therapy-induced 7 + 3 drug-DNA adducts determines cytotoxicity and clinical response...
September 10, 2018: Chemical Research in Toxicology
Hamid Reza Kalhor, Alireza Nazari Khodadadi
Conformational diseases, constituting a large number of diseases, have been connected with protein misfolding, leading to aggregation known as amyloid fibrils. Mainly due to the lack of detailed molecular mechanisms, there has not been an effective drug to combat amyloid-associated diseases. Recently, a small organic pyridazine-based molecule (RS-0406) has shown significant reductions in amyloid fibrils in both in vitro and in vivo animal studies. However, no information on molecular details of inhibition for the small molecule has been reported...
September 10, 2018: Chemical Research in Toxicology
Silvia Balbo, Irina Stepanov
The popularity of e-cigarettes is growing exponentially. Yet, the health risks associated with their use remain unclear, mainly due to the fact that they are not "one product", but a combination of ever-evolving designs, flavors, brands, and modes of use. Research needs to better understand how these variables affect toxicity.
September 6, 2018: Chemical Research in Toxicology
Rebekah E Wharton, Geovannie Ojeda-Torres, Brady Cunningham, Melanie C Feyereisen, Kasey L Hill, Nicole L Abbott, Craig Seymour, Donna Hill, Johnsie Lang, Elizabeth I Hamelin, Rudolph C Johnson
Microcystins are toxins produced by many cyanobacteria species, which are often released into waterways during blue-green algal blooms in freshwater and marine habitats. The consumption of microcystin-contaminated water is a public health concern as these toxins are recognized tumor promoters and are hepatotoxic to humans and animals. A method to confirm human exposures to microcystins is needed; therefore, our laboratory has developed an immunocapture liquid chromatography tandem mass spectrometry (LC-MS/MS) method targeting the conserved adda portion of microcystins for the quantitation of a prevalent and highly toxic congener of microcystin, microcystin-LR (MC-LR)...
September 5, 2018: Chemical Research in Toxicology
Chunyan Wang, Cheng Wang, Fang Liu, Shuo Rainosek, Tucker A Patterson, William Slikker, Xianlin Han
Numerous studies have demonstrated that treatment with high dose anesthetics for a prolonged duration induces brain injury in infants. However, whether anesthetic treatment leading to neurotoxicity is associated with alterations in lipid metabolism and homeostasis is still unclear. This review first outlines the lipidomics tools for analysis of lipid molecular species that can inform alterations in lipid species after anesthetic exposure. Then the available data indicating anesthetics cause changes in lipid profiles in the brain and serum of infant monkeys in preclinical studies are summarized, and the potential mechanisms leading to the altered lipid metabolism and their association with anesthetic-induced brain injury are also discussed...
September 4, 2018: Chemical Research in Toxicology
Arnold S Groehler, Dominic Najjar, Suresh S Pujari, Dewakar Sangaraju, Natalia Y Tretyakova
1,3-Butadiene (BD) is an environmental and occupational toxicant classified as a human carcinogen. BD is metabolically activated by cytochrome P450 monooxygenases to 3,4-epoxy-1-butene (EB), which alkylates DNA to form a range of nucleobase adducts. Among these, the most abundant are the hydrolytically labile N7-guanine adducts such as N7-(2-hydroxy-3-buten-1-yl)-guanine (N7-EB-dG). We now report that N7-EB-dG can be converted to the corresponding ring open N6 -(2-deoxy-d- erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5- N-(2-hydroxy-3-buten-1-yl)-formamidopyrimidine (EB-Fapy-dG) adducts...
September 4, 2018: Chemical Research in Toxicology
Stephanie N Bamberger, Chanchal K Malik, Markus W Voehler, Summer K Brown, Hope Pan, Tracy L Johnson-Salyard, Carmelo J Rizzo, Michael P Stone
The most common lesion in DNA occurring due to clinical treatment with Temozolomide or cellular exposures to other methylating agents is 7-methylguanine (N7-Me-dG). It can undergo a secondary reaction to form N6 -(2-deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5- N-methylformamidopyrimidine (MeFapy-dG). MeFapy-dG undergoes epimerization in DNA to produce either α or β deoxyribose anomers. Additionally, conformational rotation around the formyl bond, C5- N5 bond, and glycosidic bond may occur...
August 31, 2018: Chemical Research in Toxicology
Natalia Tretyakova, Yinsheng Wang
No abstract text is available yet for this article.
August 30, 2018: Chemical Research in Toxicology
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