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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/28545969/polyphenols-protect-mitochondrial-membrane-against-permeabilization-induced-by-hewl-oligomers-possible-mechanism-of-action
#1
Shaqayeq Roqanian, Ali Akbar Meratan, Shahin Ahmadian, Mahshid Shafizadeh, Atiyeh Ghasemi, Leila Karami
Increasing body of evidence suggests that polyphenols frequently interacting with amyloid aggregates and/or interfering with aggregate species to bind biomembranes may serve as a therapeutic approach for the treatment of amyloid-related diseases. Hence, in the present study, the possible effects of three naturally occurring polyphenols including Curcumin, Quercetin, and Resveratrol on mitochondrial membrane permeabilization induced by Hen Egg White Lysozyme (HEWL) oligomers were investigated. Our results indicated that pre-incubation of mitochondrial homogenate with polyphenols considerably inhibit membrane permeabilization in a concentration dependent manner...
May 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28545724/the-role-of-ca-2-in-cell-death-caused-by-oxidative-glutamate-toxicity-and-ferroptosis
#2
REVIEW
Pamela Maher, Klaus van Leyen, Partha Narayan Dey, Birgit Honrath, Amalia Dolga, Axel Methner
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this...
May 12, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28545672/enhancement-of-apoptotic-activities-on-brain-cancer-cells-via-the-combination-of-%C3%AE-tocotrienol-and-jerantinine-a
#3
Ibrahim Babangida Abubakar, Kuan-Hon Lim, Toh-Seok Kam, Hwei-San Loh
BACKGROUND: γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28541776/enantioselective-apoptosis-and-oxidative-damage-induced-by-individual-isomers-of-profenofos-in-primary-hippocampal-neurons
#4
Xian T Lu, Yun Ma, Hang J Zhang, Mei Q Jin, Jun H Tang
The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L(-1). The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L(-1) (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L(-1) (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23...
May 25, 2017: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
https://www.readbyqxmd.com/read/28537927/wx-132-18b-a-novel-microtubule-inhibitor-exhibits-promising-anti-tumor-effects
#5
Fang Guan, Rui Ding, Qi Zhang, Wei Chen, Feifei Li, Long Long, Wei Li, Linna Li, Dexuan Yang, Lan Xie, Shoujun Yuan, Lili Wang
Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs) with higher bioactivity and lower toxicity than currently marketed drugs. WX-132-18B, a novel structural compound synthesized at our institute, specifically bound to the colchicine-binding site on tubulin rather than the vinblastine site, and concentration-dependently reduced microtubule content via depolymerization. It exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine, vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase, triggering tumor cell apoptosis, promoting nuclear membrane permeability, reducing mitochondrial membrane potential, and disrupting the redox system balance...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536862/mechanisms-of-hepatotoxicity-associated-with-the-monocyclic-%C3%AE-lactam-antibiotic-bal30072
#6
Franziska Paech, Simon Messner, Jochen Spickermann, Mathias Wind, Anne-Hortense Schmitt-Hoffmann, Anne Therese Witschi, Brett A Howell, Rachel J Church, Jeff Woodhead, Marc Engelhardt, Stephan Krähenbühl, Martina Maurer
BAL30072 is a new monocyclic β-lactam antibiotic under development which provides a therapeutic option for the treatment of severe infections caused by multi-drug-resistant Gram-negative bacteria. Despite the absence of liver toxicity in preclinical studies in rats and marmosets and in single dose clinical studies in humans, increased transaminase activities were observed in healthy subjects in multiple-dose clinical studies. We, therefore, initiated a comprehensive program to find out the mechanisms leading to hepatocellular injury using HepG2 cells (human hepatocellular carcinoma cell line), HepaRG cells (inducible hepatocytes derived from a human hepatic progenitor cell line), and human liver microtissue preparations...
May 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28536473/athyrium-multidentatum-doll-ching-extract-induce-apoptosis-via-mitochondrial-dysfunction-and-oxidative-stress-in-hepg2-cells
#7
Guoyuan Qi, Zhigang Liu, Rong Fan, Ziru Yin, Yashi Mi, Bo Ren, Xuebo Liu
Athyrium multidentatum (Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and molecular mechanism of AMC toxicity to HepG2 cells have not yet been elucidated. Hence, this study aimed to investigate the chemical compositions and the underlying mechanisms of the antiproliferative and apoptotic effects of AMC on HepG2...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28535465/altered-glycometabolism-in-zebrafish-exposed-to-thifluzamide
#8
Yang Yang, Wenxian Liu, Dongzhi Li, Le Qian, Bin Fu, Chengju Wang
Thifluzamide exerts toxic effects to zebrafish and causes liver mitochondrial damage. To better understand the further mechanism, adult zebrafish were exposed to a range of thifluzamide concentrations (0, 0.019, 0.19, and 1.90 mg/L) for 28 days. In response to 1.90 mg/L exposure, liver glycogen significantly increased and blood glucose decreased. The expression of genes related to glycometabolism showed corresponding changes. Genes related to mtDNA replication and transcription and genes participating in mitochondrial complexes showed altered expression, which might lead to the inhibition of the tricarboxylic acid cycle (TCA)...
May 10, 2017: Chemosphere
https://www.readbyqxmd.com/read/28534083/synthetic-alpha-synuclein-fibrils-cause-mitochondrial-impairment-and-selective-dopamine-neurodegeneration-in-part-via-inos-mediated-nitric-oxide-production
#9
Victor Tapias, Xiaoping Hu, Kelvin C Luk, Laurie H Sanders, Virginia M Lee, J Timothy Greenamyre
Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson's disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28532681/resveratrol-protects-neuronal-like-cells-expressing-mutant-huntingtin-from-dopamine-toxicity-by-rescuing-atg4-mediated-autophagosome-formation
#10
Chiara Vidoni, Eleonora Secomandi, Andrea Castiglioni, Mariarosa A B Melone, Ciro Isidoro
Parkinsonian-like motor deficits in Huntington's Disease (HD) patients are associated with abnormal dopamine neurotransmission in the striatum. Dopamine metabolism leads to the formation of oxidized dopamine quinones that exacerbates mitochondrial dysfunction with production of reactive oxygen species (ROS) that eventually lead to neuronal cell death. We have previously shown that dopamine-induced oxidative stress triggers apoptotic cell death in dopaminergic neuroblastoma SH-SY5Y cells hyper-expressing the mutant polyQ Huntingtin (polyQ-Htt) protein...
May 19, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28532211/rotenone-induces-nephrotoxicity-in-rats-oxidative-damage-and-apoptosis
#11
Xiao-Wen Jiang, Lu Qiao, Xin-Xin Feng, Lin Liu, Qing-Wei Wei, Xue-Wei Wang, Wen-Hui Yu
Previous studies have examined rotenone toxicity on the human central nervous system, especially in the pathogenesis of Parkinson's disease, but few have investigated the effects of rotenone on the kidney. Here, rotenone-induced nephrotoxicity was evaluated by determining morphological, biochemical, oxidative stress-related, and apoptotic factor alterations in rat renal tissue. Morphological and biochemical analyses showed that rotenone administration to rats damaged renal tissue. Western blot results revealed that rotenone induced oxidative damage, causing overproduction of glutathione, malonaldehyde, and reactive oxygen species (ROS), and inhibiting superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity...
May 22, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28532006/mitochondrial-targeted-fluorescent-probe-with-aie-characteristics-for-bioimaging
#12
Xiaodan Lu, Meirong Hou, Qi Xia, Chenggong Yan, Yikai Xu, Ruiyuan Liu
In this work, a new benzothiazole based mitochondrial tracker, Bth-Mito, is synthesized by with 2-benzothiazoleacetonitrile and 4-(diethylamino)-benzaldehyde. Bth-Mito is weakly fluorescent when dissolved in the good solvent but becomes highly emissive in poor solvents, showing a phenomenon of aggregation-induced emission. Bth-Mito shows the greatest potentials for bioimaging applications in view of low cytotoxicity and high photostability. Bth-Mito could penetrate cells to give stable green fluorescence, even after continuous irradiation, making it suitable candidate for time-lapse and long-term bioimaging application...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28531802/anti-inflammatory-and-antioxidant-effect-of-cerium-dioxide-nanoparticles-immobilized-on-the-surface-of-silica-nanoparticles-in-rat-experimental-pneumonia
#13
Z Serebrovska, R J Swanson, V Portnichenko, A Shysh, S Pavlovich, L Tumanovska, A Dorovskych, V Lysenko, V Tertykh, Y Bolbukh, V Dosenko
A massage with the potent counter-inflammatory material, cerium dioxide nanoparticles, is promising and the antioxidant properties of CeO2 are considered the main, if not the only, mechanism of this action. Nevertheless, the elimination of ceria nano-particles from the organism is very slow and there is a strong concern for toxic effect of ceria due to its accumulation. To overcome this problem, we engineered a combined material in which cerium nanoparticles were immobilized on the surface of silica nanoparticles (CeO2 NP), which is shown to be easily removed from an organism and could be used as carriers for nano-ceria...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28530558/high-content-analysis-technology-for-evaluating-the-joint-toxicity-of-sunset-yellow-and-sodium-sulfite-in-vitro
#14
Daofeng Qu, Yanpei Gu, Lifang Feng, Jianzhong Han
Foods contain various additives that affect our daily lives. At present, food additive safety evaluation standards are based on the toxicity of single additives, but food additives are often used in combination and may have additive, synergistic or antagonistic actions. The current study investigated the toxicity of food additives and mechanisms of damage in HepG2 cells using High Content Analysis (HCA). We used the CCK-8 assay to determine cell viability, providing an experimental basis for determining the safety of food additives...
October 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#15
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28529047/bezafibrate-prevents-mitochondrial-dysfunction-antioxidant-system-disturbance-glial-reactivity-and-neuronal-damage-induced-by-sulfite-administration-in-striatum-of-rats-implications-for-a-possible-therapeutic-strategy-for-sulfite-oxidase-deficiency
#16
Mateus Grings, Alana Pimentel Moura, Belisa Parmeggiani, Julia Tauna Pletsch, Gabriela Miranda Fernandez Cardoso, Pauline Maciel August, Cristiane Matté, Angela T S Wyse, Moacir Wajner, Guilhian Leipnitz
Sulfite accumulates in tissues of patients affected by sulfite oxidase (SO) deficiency, a neurometabolic disease characterized by seizures and progressive encephalopathy, often resulting in early death. We investigated the effects of sulfite on mitochondrial function, antioxidant system, glial reactivity and neuronal damage in rat striatum, as well as the potential protective effects of bezafibrate on sulfite-induced toxicity. Thirty-day-old rats were intrastriatally administered with sulfite (2μmol) or NaCl (2μmol; control) and euthanized 30min after injection for evaluation of biochemical parameters and western blotting, or 7days after injection for analysis of glial reactivity and neuronal damage...
May 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28528260/hexavalent-chromium-induced-oxidative-stress-and-apoptosis-in-pycnoporus-sanguineus
#17
Mi Feng, Hua Yin, Hui Peng, Zehua Liu, Guining Lu, Zhi Dang
White rot fungi have been proved to be a promising option for the removal of heavy metals, understanding their toxic response to heavy metals is conducive to developing and popularizing fungi-based remediation technologies so as to lessen the hazard of heavy metals. In this study, Cr(VI)-induced oxidative stress and apoptosis in Pycnoporus sanguineus, a species of white rot fungi were investigated. The results suggested that high level of Cr(VI) promoted the formation of ROS, including H2O2, O2(•-) and ·OH...
May 18, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28527997/zinc-oxide-nanoparticles-mediated-cytotoxicity-mitochondrial-membrane-potential-and-level-of-antioxidants-in-presence-of-melatonin
#18
Sruthi S, N Millot, Mohanan Pv
Zinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products and are currently being investigated for biomedical applications. However, they have the potential to interact with macromolecules like proteins, lipids and DNA within the cells which makes the safe biomedical application difficult. The toxicity of the ZnO NP is mainly attributed reactive oxygen species (ROS) generation. Different strategies like iron doping, polymer coating and external supply of antioxidants have been evaluated to minimize the toxic potential of ZnO NPs...
May 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28527893/chemistry-and-biology-of-reactive-species-with-special-reference-to-the-antioxidative-defence-status-in-pancreatic-%C3%AE-cells
#19
REVIEW
Sigurd Lenzen
BACKGROUND: Diabetes mellitus is a serious metabolic disease. Dysfunction and subsequent loss of the β-cells in the islets of Langerhans through apoptosis ultimately cause a life-threatening insulin deficiency. The underlying reason for the particular vulnerability of the β-cells is an extraordinary sensitivity to the toxicity of reactive oxygen and nitrogen species (ROS and RNS) due to its low antioxidative defense status. SCOPE REVIEW: This review considers the different aspects of the chemistry and biology of the biologically most important reactive species and their chemico-biological interactions in the β-cell toxicity of proinflammatory cytokines in type 1 diabetes and of lipotoxicity in type 2 diabetes development...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28527359/nanocubes-of-indium-oxide-induce-cytotoxicity-and-apoptosis-through-oxidative-stress-in-human-lung-epithelial-cells
#20
Maqusood Ahamed, Mohd Javed Akhtar, M A Majeed Khan, Hisham A Alhadlaq, Ali Aldalbahi
The demand for semiconductor indium oxide (In2O3) nanocrystals is increasing because of their diverse applications, including in biomedicine. However, there is a scarcity of studies on the biological interaction of indium oxide nanocrystals. Here, we explored the underlying mechanisms of toxicity induced by indium oxide nanocubes in human lung epithelial (A549) cells. Prepared indium oxide nanocubes were crystalline with an average size of 21nm. Biointeraction studies have shown that indium oxide nanocubes induce cell viability reduction and cell membrane damage in a dose- and time-dependent manner...
May 9, 2017: Colloids and Surfaces. B, Biointerfaces
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