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Amal Tahri, Amina Lahyani, Rim Kallel, Fatma Ayadi, Tahia Boudawara, Zouheir Sahnoun
Imipenem/cilastatin is a broad-spectrum β-lactam antibiotic used to treat several bacterial infections. The present study was designed to validate the nephrotoxic effect of this drug in rats and to explore its potentional urolithiatic effect. Thirty two Wistar rats were randomly divided into four groups: three experimental groups treated with different imipenem/cilastatin dosages (30, 50 and 80 mg/kg/day) and a control group.The experimental groups were given intraperitoneal imipenem/cilastatin injections twice daily for 7 days, and the control group was given intraperitoneal vehicle NaCl 0...
May 17, 2018: Toxicology
Hiroyuki Oka, Koichi Masuno, Takeki Uehara, Toru Okamoto, Yoshiharu Matsuura, Toru Nakano, Shinpei Yamaguchi
The genotoxic potential of drugs is a serious problem, and its evaluation is one of the most critical processes of drug development. Although the comet assay of compound-exposed tissue is a frequently used genotoxicity test, its high false-positive rate is a major complication, and we consistently obtained false-positive results using the comet assay of mouse liver for nine hepatotoxic non-genotoxins (NGTXs). To identify novel genotoxin (GTX)-specific biomarkers, we screened the expression of 750 microRNAs (miRNAs) in the livers of mice treated with GTXs or NGTXs...
May 16, 2018: Toxicology
Marta Goschorska, Irena Baranowska-Bosiacka, Izabela Gutowska, Maciej Tarnowski, Katarzyna Piotrowska, Emilia Metryka, Krzysztof Safranow, Dariusz Chlubek
Inflammation is an important factor in the development of many diseases of the central nervous system, including Alzheimer's disease and other types of dementia. ‪Given that acetylcholinesterase inhibitors are also currently believed to have anti-inflammatory properties, the purpose of this study was to investigate the effect of acetylcholinesterase inhibitors (rivastigmine, donepezil) on cyclooxygenase activity and expression using the proinflammatory action of fluoride (F- ) on cultured macrophages obtained from THP-1 monocytes...
May 16, 2018: Toxicology
Maja Katalinić, Goran Šinko, Nikolina Maček Hrvat, Tamara Zorbaz, Anita Bosak, Zrinka Kovarik
The antidotal property of oximes is attributed to their ability to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP) such as pesticides and nerve warfare agents. Understanding their interactions within the active site of phosphylated AChE is of great significance for the search for more efficient reactivators, especially in the case of the most resistant OP to reactivation, tabun. Therefore, herein we studied the interactions and reactivation of tabun-inhibited AChE by site-directed mutagenesis and a series of bispyridinium oximes...
May 14, 2018: Toxicology
Ying Tang, Rui Cai, Ding Cao, Xue Kong, Yongbo Lu
This study identifies the phototoxic potential of commercial titanium dioxide nanoparticles (TiO2 NPs) used in sunscreens and consumer products by employing a tiered testing approach comprising physicochemical, in vitro and ex vivo tests. Our results revealed that all the test samples of TiO2 NPs, varied in surface coating, crystallinity and primary particle size, produced hydroxyl radicals upon UVA photoexcitation as determined by electron spin resonance (ESR) spectroscopy. Their phototoxic potentials were assessed first by combining the validated 3T3 neutral red uptake phototoxicity test and red blood cell phototoxicity test and subsequently in ex vivo models of chick chorioallantoic membrane (CAM) and reconstructed human 3D skin model (H3D)...
May 14, 2018: Toxicology
Jun Kang, Jiufei Duan, Jing Song, Chen Luo, Hong Liu, Baizhan Li, Xu Yang, Wei Yu, Mingqing Chen
Several epidemiological and experimental studies indicate a positive association between exposure to formaldehyde or phthalates and allergic asthma. However, nothing is yet known about the effects of exposure to formaldehyde and phthalates together, nor the role of each on allergic asthma. Here, we investigated the effects of a combined exposure to formaldehyde and diisononyl phthalate (DINP) on asthma-like pathology in mice, and determined the underlying mechanisms implicated in NF-κB and ROS. Mice were exposed to formaldehyde and/or DINP and sensitization with OVA...
May 11, 2018: Toxicology
Lawrence H Lash, Caroline A Lee, Clynn Wilker, Vishal Shah
The role of plasma membrane transporters in the nephrotoxicity of two antiretroviral drugs, cidofovir and tenofovir, was studied in primary cultures of human proximal tubular (hPT) cells. Cells were grown on Transwell filter inserts to maintain epithelial polarity and access to either the apical or basolateral plasma membrane. The function of relevant membrane transporters, organic anion transporter 1 and 3 (OAT1/3), P-glycoprotein (multidrug resistance protein-1; P-gp or MDR1), and organic cation transporter 2 (OCT2), was validated by measurements of apical-to-basolateral and basolateral-to-apical fluxes of furosemide, digoxin, and metformin, respectively...
May 5, 2018: Toxicology
Simona Strapáčová, Petra Brenerová, Pavel Krčmář, Patrik Andersson, Karin I van Ede, Majorie B M van Duursen, Martin van den Berg, Jan Vondráček, Miroslav Machala
Toxicity of dioxin-like compounds (DLCs), such as polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls, is largely mediated via aryl hydrocarbon receptor (AhR) activation. AhR-mediated gene expression can be tissue-specific; however, the inducibility of AhR in the lungs, a major target of DLCs, remains poorly characterized. In this study, we developed relative effective potencies (REPs) for a series of DLCs in both rodent (MLE-12, RLE-6TN) and human (A549, BEAS-2B) lung and bronchial epithelial cell models, using expression of both canonical (CYP1A1, CYP1B1) and less well characterized (TIPARP, AHRR, ALDH3A1) AhR target genes...
May 5, 2018: Toxicology
Tássia R Costa, Martin K Amstalden, Diego L Ribeiro, Danilo L Menaldo, Marco A Sartim, Alexandre F Aissa, Lusânia M G Antunes, Suely V Sampaio
Snake venom L-amino acid oxidases (SV-LAAOs) are enzymes of great interest in research due to their many biological effects with therapeutic potential. CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma snake venom, is a well described SV-LAAO with immunomodulatory, antiparasitic, microbicidal, and antitumor effects. In this study, we evaluated the genotoxic potential of this enzyme in human peripheral blood mononuclear cells (PBMC) and HepG2 tumor cells, as well as its interaction with these cells, its impact on the expression of DNA repair and antioxidant pathway genes, and reactive oxygen species (ROS)-induced intracellular production...
May 5, 2018: Toxicology
Michael G Borland, Ellen M Kehres, Christina Lee, Ashley L Wagner, Brooke E Shannon, Prajakta P Albrecht, Bokai Zhu, Frank J Gonzalez, Jeffrey M Peters
To examine the functional role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and PPARγ in skin cancer, stable cell lines were created in the A431 human squamous cell carcinoma cell line. Expression of PPAR target genes was greatly enhanced in response to ligand activation of PPARβ/δ or PPARγ in A431 cells expressing these receptors. PPARβ/δ expression blocked the cell cycle at the G2/M phase, and this effect was increased by ligand activation. Ligand activation of PPARβ/δ markedly inhibited clonogenicity as compared to vehicle-treated controls...
May 3, 2018: Toxicology
Sushma, Hridyesh Kumar, Iqbal Ahmad, Pradip Kumar Dutta
In recent years with the advancement of nanotoxicology, the scientific communities drastically increased the investigation of the potential toxicity of nanominerals which are present in all atmospheres as well as are used in a variety of applications. In this study, we reported how Quartz Nanoparticles (QNPs) depending on concentration induces different signature ER stress markers in A549 cells. QNPs induced concentration-dependent decrease in cell viability and this concentration dependent toxicity intensifies production of reactive oxygen species leading to oxidative stress and inflammation...
May 3, 2018: Toxicology
Xiaoyuan Zhang, Matthew C Williams, Otgonchimeg Rentsendorj, Felice D'Agnillo
Chemically modified hemoglobin (Hb)-based oxygen carriers are promising oxygen replacement therapeutics however their potential renal effects are not fully understood. Using a guinea pig exchange transfusion model, we examined the effects of glutaraldehyde-polymerized bovine hemoglobin (HbG) on the permeability and integrity of the glomerular filtration barrier (GFB), which is comprised of podocytes, fenestrated endothelium, and the glomerular basement membrane. HbG induced marked proteinuria characterized in part by the loss of high molecular weight proteins, including albumin, immunoglobulin, and transferrin, at 4 and 12 h post-infusion that resolved by 72 h...
April 22, 2018: Toxicology
Mina Suh, Deborah Proctor, Grace Chappell, Julia Rager, Chad Thompson, Susan Borghoff, Lavorgie Finch, Robert Ellis-Hutchings, Karin Wiench
Lower alkyl acrylate monomers include methyl-, ethyl-, n-butyl-, and 2-ethylhexyl acrylate. These acrylates are used in the manufacture of acrylic polymers and copolymers for plastics, food packaging, adhesives, and cosmetic formulations. Although there is limited potential for human environmental exposure, occupational exposure can occur via inhalation and dermal contact. Recently, new genotoxicity data have been generated, along with in silico and in vitro read-cross analyses, for these acrylates. The availability of high-throughput screening (HTS) data through the ToxCast™/Tox21 databases allows for consideration of computational toxicology and organization of these data according to the ten key characteristics of carcinogens...
April 21, 2018: Toxicology
Kun Sheng, Hua Zhang, Jianming Yue, Wei Gu, Chao Gu, Haibin Zhang, Wenda Wu
T-2 toxin, a potent type A trichothecene mycotoxin, is produced by various Fusarium species and can negatively impact animal and human health. Although anorexia induction is a common hallmark of T-2 toxin-induced toxicity, the underlying mechanisms for this adverse effect are not fully understood. The goal of this study was to determine the roles of two gut satiety hormones, glucose-dependent insulinotropic polypeptide (GIP) and Peptide YY3-36 (PYY3-36 ) in anorexia induction by T-2 toxin. Elevations of plasma GIP and PYY3-36 markedly corresponded to anorexia induction following oral exposure to T-2 toxin using a nocturnal mouse anorexia model...
April 21, 2018: Toxicology
Paula Moyano, María Teresa Frejo, María José Anadon, José Manuel García, María Jesús Díaz, Margarita Lobo, Emma Sola, Jimena García, Javier Del Pino
Chlorpyrifos (CPF) is an organophosphate insecticide described to induce cognitive disorders, both after acute and repeated administration. However, the mechanisms through which it induces these effects are unknown. CPF has been reported to produce basal forebrain cholinergic neuronal cell death, involved on learning and memory regulation, which could be the cause of such cognitive disorders. Neuronal cell death was partially mediated by oxidative stress generation, P75NTR and α7 -nAChRs gene expression alteration triggered through acetylcholinesterase (AChE) variants disruption, suggesting other mechanisms are involved...
April 14, 2018: Toxicology
Żaneta Broniowska, Joanna Ślusarczyk, Beata Starek-Świechowicz, Ewa Trojan, Bartosz Pomierny, Weronika Krzyżanowska, Agnieszka Basta-Kaim, Bogusława Budziszewska
Benzophenones used as UV filters, in addition to the effects on the skin, can be absorbed into the blood and affect the function of certain organs. So far, their effects on the sex hormone receptors and gonadal function have been studied, but not much is known about their potential action on other systems. The aim of the present study was to determine the effect of benzophenone-2 (BP-2) on immune system activity, hypothalamic-pituitary-thyroid (HPT) axis activity and hematological parameters. BP-2 was administered dermally, twice daily at a dose of 100 mg/kg for 4-weeks to male Wistar rats...
April 13, 2018: Toxicology
Martin Ezechiáš, Tomáš Cajthaml
Receptor ligands in mixtures may produce effects that are greater than the effect predicted from their individual dose-response curves. The historical basis for predicting the mixture effect is based on Loewés concept and its mathematical formulation. This concept considers compounds with constant relative potencies (parallel dose-response curves) and leads to linear additive isoboles. These lines serve as references for distinguishing additive from nonadditive interactions according to the positions of the experimental data on or outside of the lines...
April 13, 2018: Toxicology
Marie Stiborová, Helena Dračínská, Lucie Bořek-Dohalská, Zuzana Klusoňová, Jana Holecová, Markéta Martínková, Heinz H Schmeiser, Volker M Arlt
Endocrine disruptors (EDs) are compounds that interfere with the balance of the endocrine system by mimicking or antagonising the effects of endogenous hormones, by altering the synthesis and metabolism of natural hormones, or by modifying hormone receptor levels. The synthetic estrogen 17α-ethinylestradiol (EE2) and the environmental carcinogen benzo[a]pyrene (BaP) are exogenous EDs whereas the estrogenic hormone 17β-estradiol is a natural endogenous ED. Although the biological effects of these individual EDs have partially been studied previously, their toxicity when acting in combination has not yet been investigated...
April 9, 2018: Toxicology
Quaiser Saquib, Maqsood A Siddiqui, Javed Ahmad, Sabiha M Ansari, Hend A Al-Wathnani, Christopher Rensing
In this study, HepG2 cells were exposed to 6-hydroxy- 2,2',4,4'-tetrabromodiphenyl ether (6-OHBDE-47) for 3 and 6 days for monitoring cytotoxic effects and alterations in its transcriptomic profile. MTT assay showed that cells exposed to 6-OHBDE-47 (50 nM) exhibited 48.5% and 53.7% decline in cell survival after 3 and 6 days. Neutral red uptake (NRU) assay also demonstrated 47.1% and 56% reduction in cell survival at 50 nM, indicating lysosomal toxicity. The flow cytometric data confirmed an increase in intracellular reactive oxygen species (ROS) and mitochondrial dysfunction (ΔYm)...
March 27, 2018: Toxicology
Zainab Fatima, Pu Guo, Deyu Huang, Qirong Lu, Qinghua Wu, Menghong Dai, Guyue Cheng, Dapeng Peng, Yanfei Tao, Muhammad Ayub, Muhammad Tahir Ul Qamar, Muhammad Waqar Ali, Xu Wang, Zonghui Yuan
T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (△Ym) upon exposure to the T-2 toxin...
March 19, 2018: Toxicology
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