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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/28822104/comparison-of-the-toxic-effects-of-quinolinic-acid-and-3-nitropropionic-acid-in-c-elegans-involvement-of-the-skn-1-pathway
#1
Ilan Kotlar, Aline Colonnello, María Fernanda Aguilera-González, Daiana Silva Avila, María Eduarda de Lima, Rodolfo García-Contreras, Alma Ortíz-Plata, Félix Alexandre Antunes Soares, Michael Aschner, Abel Santamaría
The tryptophan metabolite, quinolinic acid (QUIN), and the mitochondrial toxin 3-nitropropionic acid (3-NP) are two important tools for toxicological research commonly used in neurotoxic models of excitotoxicity, oxidative stress, energy depletion, and neuronal cell death in mammals. However, their toxic properties have yet to be explored in the nematode Caenorhabditis elegans (C. elegans) for the establishment of novel, simpler, complementary, alternative, and predictive neurotoxic model of mammalian neurotoxicity...
August 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28821289/transcriptome-wide-analyses-indicate-mitochondrial-responses-to-particulate-air-pollution-exposure
#2
Ellen Winckelmans, Tim S Nawrot, Maria Tsamou, Elly Den Hond, Willy Baeyens, Jos Kleinjans, Wouter Lefebvre, Nicolas Van Larebeke, Martien Peusens, Michelle Plusquin, Hans Reynders, Greet Schoeters, Charlotte Vanpoucke, Theo M de Kok, Karen Vrijens
BACKGROUND: Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM10 exposure. METHODS: Whole genome gene expression was measured in peripheral blood of 98 adults (49% women). We performed linear regression analyses stratified by sex and adjusted for individual and temporal characteristics to investigate alterations in gene expression induced by short-term (week before blood sampling) and medium-term (month before blood sampling) PM10 exposure...
August 18, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28820078/effects-of-excitotoxic-lesion-with-inhaled-anesthetics-on-nervous-system-cells-of-rodents
#3
Maria Fernanda Quiroz Padilla, Gemma Guillazo-Blanch, Magdy Sanchez, Maria Andrea Dominguez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28819542/mulberry-fruit-extract-affords-protection-against-ethyl-carbamate-induced-cytotoxicity-and-oxidative-stress
#4
Wei Chen, Yuting Li, Tao Bao, Vemana Gowd
Ethyl carbamate (EC) is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE) on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28819410/characterization-of-the-role-of-the-malate-dehydrogenases-to-lung-tumor-cell-survival
#5
Boxi Zhang, Johan Tornmalm, Jerker Widengren, Helin Vakifahmetoglu-Norberg, Erik Norberg
Cellular compartmentalization of biochemical processes in eukaryotic cells is critical for many functions including shuttling of reducing equivalents across membranes. Although coordination of metabolic flux between different organelles is vital for cell physiology, its impact on tumor cell survival is not well understood. By using an integrative approach, we have dissected the role of the key metabolic enzymes Malate dehydrogenases (MDH1 and MDH2) to the survival of Non-small Cell Lung Carcinomas. Here, we report that while both the MDH1 (cytosolic) and the MDH2 (mitochondrial) enzymes display elevated levels in patients compared to normal counterparts, only high expression of MDH1 is associated with poor prognosis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819074/-molecular-pathogenesis-of-polyglutamine-diseases
#6
Yuji Takahashi
Polyglutamine diseases result from gain-of-function mutations. The expanded polyglutamine tracts lead to conformational changes in proteins, resulting in their aggregation. The intermediates including monomers or oligomers, are more toxic than the aggregates to neurons. At the molecular level, protein misfolding, transcriptional dysregulation, deranged calcium homeostasis, impaired cytoskeleton/axonal transport, mitochondrial dysfunction, and RNA toxicity contribute to disease progression. Understanding the underlying pathogenesis facilitates development of therapy for polyglutamine diseases...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28817209/huntington-s-disease-a-clinical-review
#7
Peter McColgan, Sarah J Tabrizi
Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6-13.7 individuals per 100,000. It is characterised by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein...
August 17, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28812436/the-mechanism-of-protective-effect-of-crocin-against-liver-mitochondrial-toxicity-caused-by-arsenic-iii
#8
Bahareh Sadat Yousefsani, Jalal Pourahmad, Hossein Hosseinzadeh
In this study, we want to understand whether crocin could prevent mitochondrial damage caused by As III. For this purpose, we determined different mitochondrial toxicity endpoints caused by As III. We evaluated mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial outer membrane integrity and cytochrome c release. Our results showed that pretreatment with crocin at a concentration of 25 µg/ml significantly (P < 0.001) reduced As III induced mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse and mitochondrial swelling...
August 16, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28811603/2-4-6-trinitrotoluene-induces-apoptosis-via-ros-regulated-mitochondrial-dysfunction-and-endoplasmic-reticulum-stress-in-hepg2-and-hep3b-cells
#9
Hung-Yu Liao, Chih-Ming Kao, Chao-Ling Yao, Po-Wei Chiu, Chun-Chen Yao, Ssu-Ching Chen
2,4,6-trinitrotoluene (TNT) has been reported to cause numerous adverse effects. However, the detailed molecular mechanisms underlying TNT-induced liver toxicity need to be elucidated. In this study, we used HepG2 (p53wt) and Hep3B (p53null) cell lines to investigate the cytotoxic effects of TNT. At first, we found that TNT significantly decreased cell viability and induced DNA damage. Thereafter, through transcriptomic analysis, we observed that the diverse biological functions affected included mitochondrial dysfunction and endoplasmic reticulum (ER) stress...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810231/cr-induced-cellular-injury-and-necrosis-in-glycine-max-l-biochemical-mechanism-of-oxidative-damage-in-chloroplast
#10
Kalimuthu Balasaraswathi, Sivalingam Jayaveni, Janardhanam Sridevi, Dhanasingh Sujatha, Kavati Phebe Aaron, Chellan Rose
Chromium-induced toxicity and mechanisms of cell death involved in plants are yet to be fully elucidated. To understand the events of these processes, the stress response of the soybean plant using trivalent and hexavalent chromium compounds, namely, basic chromium sulphate (BCS) and potassium dichromate (K2Cr2O7) was investigated. The leaf surface morphology for stomatal aperture, wax deposition and presence of trichomes for chromium accumulation was examined by SEM-EDAX and light microscopy. The leaf mesophyll cell integrity was identified by trypan blue staining; chlorophyll autofluorescence, ROS generation and mitochondrial function were studied by fluorescence microscopy using different dyes...
August 2, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28807098/protective-effect-of-ozone-against-hemiscorpius-lepturus-envenomation-in-mice
#11
Parvaneh Naserzadeh, Farshad Shahi, Delavar Shahbazzadeh, Mostafa Ghanei, Khadijeh Ashtari, Yoones Panahi, Mir-Jamal Hosseini, Morteza Izadi
OBJECTIVE: Scorpion (Hemiscorpius lepturus) stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock (which can sometimes even lead to death). The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus (H. lepturus) venom in mice...
August 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28806770/increasing-creatine-kinase-activity-protects-against-hypoxia-reoxygenation-injury-but-not-against-anthracycline-toxicity-in-vitro
#12
Sevasti Zervou, Hannah J Whittington, Philip J Ostrowski, Fang Cao, Jack Tyler, Hannah A Lake, Stefan Neubauer, Craig A Lygate
The creatine kinase (CK) phosphagen system is fundamental to cellular energy homeostasis. Cardiomyocytes express three CK isoforms, namely the mitochondrial sarcomeric CKMT2 and the cytoplasmic CKM and CKB. We hypothesized that augmenting CK in vitro would preserve cell viability and function and sought to determine efficacy of the various isoforms. The open reading frame of each isoform was cloned into pcDNA3.1, followed by transfection and stable selection in human embryonic kidney cells (HEK293). CKMT2- CKM- and CKB-HEK293 cells had increased protein and total CK activity compared to non-transfected cells...
2017: PloS One
https://www.readbyqxmd.com/read/28804553/sirt3-attenuates-doxorubicin-induced-cardiac-hypertrophy-and-mitochondrial-dysfunction-via-suppression-of-bnip3
#13
Qiong Du, Bin Zhu, Qing Zhai, Bo Yu
Doxorubicin (Dox) is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by development of cardiotoxicity. Sirtuin-3 (Sirt3) is the major deacetylase within the mitochondrial matrix that plays an important role in regulation of cardiac function. This study was performed to identify the regulatory role of Sirt3 on Dox-induced cardiac hypertrophy and mitochondrial dysfunction in rats in vivo and in vitro...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28800409/cytotoxic-effects-of-the-proton-pump-inhibitor-omeprazole-on-the-non-target-marine-microalga-tetraselmis-suecica
#14
Marta Seoane, Marta Esperanza, Ángeles Cid
Omeprazole (OMP) is one of the most commonly used drugs for the treatment of gastro-intestinal disorders. Although it is daily consumed in high quantities and commonly detected in waters worldwide, relatively little is known about its ecotoxicity. The aim of this study was to evaluate the potential acute toxicity of increasing concentrations of OMP on the marine microalga Tetraselmis suecica analysing several cytotoxicity biomarkers by flow cytometry after 24h of exposure. Results showed that OMP caused a decrease in growth and autofluorescence, an increase in cellular volume and intracellular complexity, hyperpolarization of cytoplasmic and mitochondrial membranes and intracellular acidification...
August 2, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28798664/interplay-of-energetics-and-er-stress-exacerbates-alzheimer-s-amyloid-%C3%AE-a%C3%AE-toxicity-in-yeast
#15
Xin Chen, Markus M M Bisschops, Nisha R Agarwal, Boyang Ji, Kumaravel P Shanmugavel, Dina Petranovic
Alzheimer's disease (AD) is a progressive neurodegeneration. Oligomers of amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more toxic and prone to form oligomers. Here, we took a systems biology approach to study two humanized yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected chronological lifespan and reduced variations during cell growth...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28792756/design-synthesis-and-biological-evaluation-of-novel-selenium-containing-isocombretastatins-and-phenstatins-as-antitumor-agents
#16
Yanqing Pang, Baijiao An, Lanlan Lou, Junsheng Zhang, Jun Yan, Ling Huang, Xingshu Li, Sheng Yin
Two series of structurally-related organoselenium compounds designed by fusing the anticancer agent methyl(phenyl)selane into the tubulin polymerization inhibitors isocombretastatins or phenstatins were synthesized and evaluated for antiproliferative activity. Most of these selenium containing hybrids exhibited potent cytotoxicity against a panel of cancel cell lines, with IC50 values in the submicromolar concentration range. Among them, 11a, the 3-methylseleno derivative of isocombretastatin A-4 (isoCA-4), represented the most active compound with IC50 values of 2-34 nM against twelve cancer cell lines, including two drug-resistant cell lines...
August 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28790395/knockdown-of-hif-1%C3%AE-by-sirna-expressing-plasmid-delivered-by-attenuated-salmonella-enhances-the-antitumor-effects-of-cisplatin-on-prostate-cancer
#17
Junlian Gu, Yang Li, Jun Zeng, Bo Wang, Kun Ji, Yufeng Tang, Qing Sun
Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789971/the-use-of-high-throughput-screening-techniques-to-evaluate-mitochondrial-toxicity
#18
Lauren P Wills
Toxicologists and chemical regulators depend on accurate and effective methods to evaluate and predict the toxicity of thousands of current and future compounds. Robust high-throughput screening (HTS) experiments have the potential to efficiently test large numbers of chemical compounds for effects on biological pathways. HTS assays can be utilized to examine chemical toxicity across multiple mechanisms of action, experimental models, concentrations, and lengths of exposure. Many agricultural, industrial, and pharmaceutical chemicals classified as harmful to human and environmental health exert their effects through the mechanism of mitochondrial toxicity...
August 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28789970/mitochondrial-fusion-fission-and-mitochondrial-toxicity
#19
Joel N Meyer, Tess C Leuthner, Anthony L Luz
Mitochondrial dynamics are regulated by two sets of opposed processes: mitochondrial fusion and fission, and mitochondrial biogenesis and degradation (including mitophagy), as well as processes such as intracellular transport. These processes maintain mitochondrial homeostasis, regulate mitochondrial form, volume and function, and are increasingly understood to be critical components of the cellular stress response. Mitochondrial dynamics vary based on developmental stage and age, cell type, environmental factors, and genetic background...
August 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28782414/protective-effect-of-neuropeptide-apelin-13-on-6-hydroxydopamine-induced-neurotoxicity-in-sh-sy5y-dopaminergic-cells-involvement-of-its-antioxidant-and-antiapoptotic-properties
#20
Elham Pooresmaeili-Babaki, Saeed Esmaeili-Mahani, Mehdi Abbasnejad, Hadi Ravan
Parkinson's disease (PD) is a severe neurodegenerative disorder characterized by the loss of brain dopaminergic neurons. Beside pharmacologic and symptomatic treatment of PD the neuroprotective therapy has recently attracted more attention. Apelin, a novel neuropeptide, and its receptors have numerous reported roles in regulating brain functions. In addition, this peptide has potent neuroprotective effects in some neurodegenerative situations. Here, the effects of apelin-13 were investigated in a cell model of PD...
August 7, 2017: Rejuvenation Research
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