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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/29222055/autophagy-plays-a-protective-role-in-mn-induced-toxicity-in-pc12-cells
#1
Qian Zhou, Xiaolong Fu, Xueting Wang, Qin Wu, Yuanfu Lu, Jingshan Shi, James E Klaunig, Shaoyu Zhou
Excessive environmental or occupational exposure to manganese (Mn) is associated with increased risk of neuron degenerative disorders. Oxidative stress and mitochondrial dysfunction are the main mechanisms of Mn mediated neurotoxicity. Selective removal of damaged mitochondria by autophagy has been proposed as a protective mechanism against neuronal toxicant-induced neurotoxicity. Whether autophagic flux plays a role in Mn-induced cytotoxicity remains to be fully elucidated. The present study was designed to investigate the effect of Mn exposure on autophagy, and how modulation of autophagic flux alters the sensitivities of cells to Mn-elicited cytotoxicity...
December 5, 2017: Toxicology
https://www.readbyqxmd.com/read/29221182/differential-modulation-of-bax-bcl-2-ratio-and-onset-of-caspase-3-7-activation-induced-by-derivatives-of-justicidin-b-in-human-melanoma-cells-a375
#2
Aljawharah Al-Qathama, Simon Gibbons, Jose M Prieto
Diphyllin and its derivatives are well known cytotoxic natural products structurally related to the anti-cancer drug podophyllotoxin. We here study their structure-activity relationship upon human melanoma cells for first time. To this end, human melanoma A375 cells were incubated with Justicidin B and its 4-methoxylated or 4-glycosylated derivatives to evaluate their selective cytotoxicity and study their effects on cell cycle distribution, caspase activation, apoptosis induction using Annexin V-FITC/PI staining, cell morphology and western blot analysis...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218782/therapy-development-in-huntington-disease-from-current-strategies-to-emerging-opportunities
#3
REVIEW
Audrey S Dickey, Albert R La Spada
Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder in which patients typically present with uncontrolled involuntary movements and subsequent cognitive decline. In 1993, a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene was identified as the cause of this disorder. This extended CAG repeat results in production of HTT protein with an expanded polyglutamine tract, leading to pathogenic HTT protein conformers that are resistant to protein turnover, culminating in cellular toxicity and neurodegeneration...
December 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29218775/comparative-proteomic-analysis-of-silver-nanoparticle-effects-in-human-liver-and-intestinal-cells
#4
Albert Braeuning, Axel Oberemm, Josephine Görte, Linda Böhmert, Sabine Juling, Alfonso Lampen
Consumers are orally exposed to nanoparticulate or soluble species of the non-essential element silver due to its use in food contact materials or as a food additive. Potential toxicity of silver nanoparticles has gained special scientific attention. A fraction of ingested ionic or particulate silver is taken up in the intestine and transported to the liver, where it may induce oxidative stress and elicit subsequent adverse responses. Here, we present a comprehensive analysis of global proteomic changes induced in human Hep G2 hepatocarcinoma cells by different concentrations of AgPURE silver nanoparticles or by corresponding concentrations of ionic silver...
December 7, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29216509/in-vitro-study-on-the-joint-hepatoxicity-upon-combined-exposure-of-cadmium-and-bde-209
#5
Lixin Wang, Miaomiao Zheng, Yu Gao, Jiansheng Cui
Joint toxicity is an important issue during the risk assessment of environmental pollutants. Contamination of heavy metals and persistent organic pollutants (POPs) under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium and decabrominated diphenyl ether (BDE-209) in environmental mediums, food chains and even human body, their potentially joint toxicities remain elusive thus far. Our investigation here with respect to the hepatotoxicity in vitro clearly demonstrated that combined exposure of cadmium and BDE-209 aggravated the injuries in hepatocytes, which was evidenced by the additive effects on the induction of remarkable morphological alternations, LDH release, cell apoptosis and necrosis, impairment of mitochondrial activity and transmembrane potential...
November 29, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29214897/ss-31-peptide-enables-mitochondrial-targeting-drug-delivery-a-promising-therapeutic-alteration-to-prevent-hair-cell-damage-from-aminoglycosides
#6
Xiao Kuang, Shuang Zhou, Weiling Guo, Zhenjie Wang, Yanhui Sun, Hongzhuo Liu
Aminoglycoside-induced hearing loss stems from damage or loss of mechanosensory hair cells in the inner ear. Intrinsic mitochondrial cell death pathway plays a key role in that cellular dysfunction for which no proven effective therapies against oto-toxicities exist. Therefore, the aim of the present study was to develop a new mitochondrial targeting drug delivery system (DDS) that provided improved protection from gentamicin. Particularly, SS-31 peptide-conjugated geranylgeranylacetone (GGA) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were constructed successfully via emulsion-solvent evaporation method...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29214717/bisphenol-a-is-an-exogenous-toxin-that-promotes-mitochondrial-injury-and-death-in-tubular-cells
#7
Enrique Bosch-Panadero, Sebastian Mas, Esther Civantos, Pedro Abaigar, Vanesa Camarero, Alberto Ruiz-Priego, Alberto Ortiz, Jesus Egido, Emilio González-Parra
BACKGROUND: Uremic toxins that accumulate in chronic kidney disease (CKD) contribute to CKD complications, such as CKD progression. Bisphenol A (BPA) is a ubiquitous environmental toxin, structurally related with p-cresol, that accumulates in CKD. Our aim was to characterize the nephrotoxic potential of BPA. Specifically, we addressed BPA toxicity over energy-demanding proximal tubular cells. METHODS: Cell death and oxidative stress were evaluated by flow cytometry and confocal microscopy in HK-2 human proximal tubular epithelial cells...
December 7, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29214156/off-target-effects-of-drugs-that-disrupt-human-mitochondrial-dna-maintenance
#8
REVIEW
Matthew J Young
Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency syndrome. Development of severe mitochondrial toxicity has been well documented in patients infected with HIV and administered NRTIs. In vitro biochemical experiments have demonstrated that the replicative mitochondrial DNA (mtDNA) polymerase gamma, Polg, is a sensitive target for inhibition by metabolically active forms of NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs)...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29213094/sodium-fluoride-exposure-exerts-toxic-effects-on-porcine-oocyte-maturation
#9
Shuang Liang, Zheng-Wen Nie, Minghui Zhao, Ying-Jie Niu, Kyung-Tae Shin, Xiang-Shun Cui
Excessive long-term fluoride intake is associated with several health problems, including infertility. However, limited information is available on the toxic effects of fluoride exposure on the female reproductive system, especially oocyte maturation. In this study, we investigated the toxic effect of sodium fluoride (NaF) exposure on porcine oocyte maturation and its possible underlying mechanisms. Our results showed that NaF exposure during porcine oocyte maturation inhibited cumulus cell expansion and impaired polar body extrusion...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207128/nr4a1-induced-increase-in-the-sensitivity-of-a-human-gastric-cancer-line-to-tnf%C3%AE-mediated-apoptosis-is-associated-with-the-inhibition-of-jnk-parkin-dependent-mitophagy
#10
Hongzhu Yan, Feng Xiao, Jue Zou, Chengmin Qiu, Weiwei Sun, Minmin Gu, Li Zhang
Tumor necrosis factor α (TNFα)-based immunotherapy is the vital host defense system against the progression of gastric cancer (GC) as a pro-inflammatory and pro-apoptotic cytokine. However, resistance limits its therapeutic efficiency. Therefore, an increasing number of studies are focusing on the development of drugs or methods with which to enhance the treatment efficacy of TNFα. Nuclear receptor subfamily 4 group A member 1 (NR4A1) has been shown to exert antitumor effects through several mechanisms, such as by inhibiting proliferation, as well as pro-apoptotic and potent pro-oxidant effects...
December 4, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29206204/antioxidants-protect-against-arsenic-induced-mitochondrial-cardio-toxicity
#11
REVIEW
Clare Pace, Ruben Dagda, Jeff Angermann
Arsenic is a potent cardiovascular toxicant associated with numerous biomarkers of cardiovascular diseases in exposed human populations. Arsenic is also a carcinogen, yet arsenic trioxide is used as a therapeutic agent in the treatment of acute promyelotic leukemia (APL). The therapeutic use of arsenic is limited due to its severe cardiovascular side effects. Many of the toxic effects of arsenic are mediated by mitochondrial dysfunction and related to arsenic's effect on oxidative stress. Therefore, we investigated the effectiveness of antioxidants against arsenic induced cardiovascular dysfunction...
December 5, 2017: Toxics
https://www.readbyqxmd.com/read/29205852/glycyrrhetinic-acid-functionalized-graphene-oxide-for-mitochondria-targeting-and-cancer-treatment-in-vivo
#12
Chao Zhang, Zunfeng Liu, Ying Zheng, Yadi Geng, Chao Han, Yamin Shi, Hongbin Sun, Can Zhang, Yijun Chen, Luyong Zhang, Qinglong Guo, Lei Yang, Xiang Zhou, Lingyi Kong
Mitochondria-mediated apoptosis (MMA) is a preferential option for cancer therapy due to the presence of cell-suicide factors in mitochondria, however, low permeability of mitochondria is a bottleneck for targeting drug delivery. In this paper, glycyrrhetinic acid (GA), a natural product from Glycyrrhiza glabra, is found to be a novel mitochondria targeting ligand, which can improve mitochondrial permeability and enhance the drug uptake of mitochondria. GA-functionalized graphene oxide (GO) is prepared and used as an effective carrier for targeted delivery of doxorubicin into mitochondria...
December 4, 2017: Small
https://www.readbyqxmd.com/read/29204172/protective-effects-of-coenzyme-q10-and-l-carnitine-against-statin-induced-pancreatic-mitochondrial-toxicity-in-rats
#13
Melina Sadighara, Jalal Pourahamad Joktaji, Valiollah Hajhashemi, Mohsen Minaiyan
Statins are widely used in patients with hyperlipidemia and whom with high risk of cardiovascular diseases. Unfortunately, statins also exert some adverse effects on the liver and pancreas and enhance the risk of type 2 diabetes mellitus. The objective of the present research was to investigate the protective effects of coenzyme Q10 (Co-Q10) and L-carnitine (LC) on statins induced toxicity on pancreatic mitochondria in vivo. Seven groups of male Wistar rats received atorvastatin (20 mg/kg, p.o.), atorvastatin + Co-Q10 (10 mg/kg, i...
December 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29204154/mitochondria-a-common-target-for-genetic-mutations-and-environmental-toxicants-in-parkinson-s-disease
#14
REVIEW
Martin P Helley, Jennifer Pinnell, Carolina Sportelli, Kim Tieu
Parkinson's disease (PD) is a devastating neurological movement disorder. Since its first discovery 200 years ago, genetic and environmental factors have been identified to play a role in PD development and progression. Although genetic studies have been the predominant driving force in PD research over the last few decades, currently only a small fraction of PD cases can be directly linked to monogenic mutations. The remaining cases have been attributed to other risk associated genes, environmental exposures and gene-environment interactions, making PD a multifactorial disorder with a complex etiology...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29203277/transcriptomic-study-of-the-toxic-mechanism-triggered-by-beauvericin-in-jurkat-cells
#15
L Escrivá, D Jennen, F Caiment, L Manyes
Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5μM; 24h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations...
December 1, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29203145/global-gene-expression-analysis-of-macrophage-response-induced-by-nonporous-and-porous-silica-nanoparticles
#16
Mostafa Yazdimamaghani, Philip J Moos, Hamidreza Ghandehari
Little is known about the global gene expression profile of macrophages in response to changes in size and porosity of silica nanoparticles (SNPs). Spherical nonporous SNPs of two different diameters, and mesoporous spherical SNPs with comparable size were characterized. Reactive oxygen species, mitochondrial membrane potential, lysosome degradation capacity, and lysosome pH were measured to evaluate the influence of nonporous and mesoporous SNPs on mitochondrial and lysosomal function. RNA-sequencing was utilized to generate transcriptional profiles of RAW264...
December 1, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29202332/chloro-triphenylphosphine-gold-i-a-forefront-reagent-in-gold-chemistry-as-apoptotic-agent-for-cancer-cells
#17
M P Chrysouli, C N Banti, N Kourkoumelis, N Panayiotou, G S Markopoulos, A J Tasiopoulos, S K Hadjikakou
The antiproliferative activity of the gold complex [Au(tpp)Cl] (1) (tpp=triphenyphosphine) against human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblast cells (MRC-5) was investigated. The compound exhibits stronger activity against MCF-7 cells than cisplatin. The apoptotic pathway, especially though the mitochondrion damage was concluded by cell cycle arrest, flow cytometry using Annexin V-Fluorescein IsoThioCyanate (FITC) and Propidium Iodide (PI) as indicators, assays and permeabilization of the mitochondrial membrane tests...
November 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29199262/impaired-bioenergetics-in-clinical-medicine-a-target-to-tackle
#18
Sergej M Ostojic
Mitochondrial energy deficit is considered a key element of different clinical pathologies - from inherited disorders of energy metabolism to drug-induced mitochondrial toxicity, to cardiometabolic and neurodegenerative diseases. However, clinical manifestations of impaired bioenergetics are not easy to recognize, with patient-reported features usually include non-pathognomonic fatigue and weakness, or exercise intolerance, while specific lab tests are missing. Although it is not clear whether poor energetics is a primary deficit or a secondary consequence of specific disorders, improving mitochondrial viability remains a challenging task in both experimental and clinical medicine...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29198728/flumioxazin-metabolism-in-pregnant-animals-and-cell-based-protoporphyrinogen-ix-oxidase-ppo-inhibition-assay-of-fetal-metabolites-in-various-animal-species-to-elucidate-the-mechanism-of-the-rat-specific-developmental-toxicity
#19
Jun Abe, Naohiko Isobe, Kazuki Mikata, Hirohisa Nagahori, Yoshikazu Naito, Hideo Saji, Masahiro Ono, Satoshi Kawamura
Flumioxazin, an N-phenylimide herbicide, inhibits protoporphyrinogen oxidase (PPO), a key enzyme in heme biosynthesis in mammals, and causes rat-specific developmental toxicity. The mechanism has mainly been clarified, but no research has yet focused on the contribution of its metabolites. We therefore conducted in vivo metabolism studies in pregnant rats and rabbits, and found 6 major known metabolites in excreta. There was no major rat-specific metabolite. The most abundant component in rat fetuses was APF, followed by flumioxazin and 5 identified metabolites...
November 30, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29197802/developing-the-next-generation-of-graphene-based-platforms-for-cancer-therapeutics-the-potential-role-of-reactive-oxygen-species
#20
REVIEW
Tanveer A Tabish, Shaowei Zhang, Paul G Winyard
Graphene has a promising future in applications such as disease diagnosis, cancer therapy, drug/gene delivery, bio-imaging and antibacterial approaches owing to graphene's unique physical, chemical and mechanical properties alongside minimal toxicity to normal cells, and photo-stability. However, these unique features and bioavailability of graphene are fraught with uncertainties and concerns for environmental and occupational exposure. Changes in the physicochemical properties of graphene affect biological responses including reactive oxygen species (ROS) production...
November 22, 2017: Redox Biology
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