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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/28647477/derivatives-of-alkyl-gallate-triphenylphosphonium-exhibit-antitumor-activity-in-a-syngeneic-murine-model-of-mammary-adenocarcinoma
#1
Liliana Peredo-Silva, Sebastián Fuentes-Retamal, Cristian Sandoval-Acuña, Mario Pavani, Juan D Maya, Vicente Castro-Castillo, Matías Madrid-Rojas, Solange Rebolledo, Ulrike Kemmerling, Eduardo Parra, Jorge Ferreira
We previously demonstrated that alkyl gallates coupled to triphenylphosphine have a selective and efficient antiproliferative effect by inducing mitochondrial uncoupling in vitro due to the increased mitochondrial transmembrane potential of tumor cells. Therefore, in this work, the in vivo antitumor activities of alkyl gallate triphenylphosphonium derivatives (TPP(+)C8, TPP(+)C10 and TPP(+)C12) were evaluated in a syngeneic murine model of breast cancer. We found that TPP(+)C10 increased the cytosolic ADP/ATP ratio and significantly increased the AMP levels in a concentration-dependent manner in TA3/Ha murine mammary adenocarcinoma cells...
June 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28646724/zinc-and-calcium-alter-the-relationship-between-mitochondrial-respiration-ros-and-membrane-potential-in-rainbow-trout-oncorhynchus-mykiss-liver-mitochondria
#2
Mahmoud S Sharaf, Don Stevens, Collins Kamunde
At excess levels, zinc (Zn) disrupts mitochondrial functional integrity and induces oxidative stress in aquatic organisms. Although much is known about the modulation of Zn toxicity by calcium (Ca) in fish, their interactions at the mitochondrial level have scarcely been investigated. Here we assessed the individual and combined effects of Zn and Ca on the relationship between mitochondrial respiration, ROS and membrane potential (ΔΨmt) in rainbow trout liver mitochondria. We tested if cation uptake through the mitochondrial calcium uniporter (MCU) is a prerequisite for Zn- and/or Ca-induced alteration of mitochondrial function...
June 12, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28645576/mechanisms-of-hepatocellular-toxicity-associated-with-new-psychoactive-synthetic-cathinones
#3
Dino Luethi, Matthias E Liechti, Stephan Krähenbühl
Synthetic cathinones are a new class of psychostimulant substances. Rarely, they can cause liver injury but associated mechanisms are not completely elucidated. In order to increase our knowledge about mechanisms of hepatotoxicity, we investigated the effect of five frequently used cathinones on two human cell lines. Bupropion was included as structurally related drug used therapeutically. In HepG2 cells, bupropion, MDPV, mephedrone and naphyrone depleted the cellular ATP content at lower concentrations (0...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28643149/surface-modification-minimizes-the-toxicity-of-silver-nanoparticles-an-in-vitro-and-in-vivo-study
#4
Balaram Das, Satyajit Tripathy, Jaydeep Adhikary, Sourav Chattopadhyay, Debasis Mandal, Sandeep Kumar Dash, Sabyasachi Das, Aditi Dey, Sankar Kumar Dey, Debasis Das, Somenath Roy
Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system...
June 22, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28642010/magnetic-nanogels-as-dual-triggered-anticancer-drug-delivery-toxicity-evaluation-on-isolated-rat-liver-mitochondria
#5
Somayeh Sadighian, Kobra Rostamizadeh, Mehrdad Hamidi, Mir-Jamal Hosseini, Hassan Hosseini-Monfared
This study aimed to evaluate bio-safety of magnetic chitosan nanogels as dual triggered drug carrier for doxorubicin through analysis of mitochondrial function. In the present study, chitosan/TPP nanogels containing magnetite nanoparticles (NPs) were prepared according to the ionotropic gelation method as novel pH-sensitive magnetic nanogels. The NPs showed outstanding entrapment efficiency for doxorubicin (76.6%) with a sustained and high extent of drug release in the acidic media (pH=5-7) compared to the neutral media...
June 19, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28641455/modulation-of-cisplatin-cytotoxic-activity-against-leiomyosarcoma-cells-by-epigallocatechin-3-gallate
#6
Irida Th Dhima, Dimitrios Peschos, Yannis V Simos, Maria I Gkiouli, Maria E Palatianou, Vasilios N Ragos, Vasiliki Kalfakakou, Angelos M Evangelou, Spyridon Ch Karkabounas
The aim of this study was to investigate the cytotoxic effect cisplatin in combination with epigallocatechin-3-gallate (EGCG) on leiomyosarcoma cells (LMS cells) in order to identify a less toxic but equally effective alternative. Assays for cell proliferation, colony formation efficiency, induction of apoptosis and cell cycle arrest were performed using the IC50 of cisplatin (8.6 μΜ) as a reference value and a concentration of EGCG (30 μΜ) that caused a non-significant reduction in cell proliferation...
June 23, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28641197/effects-of-organophosphorus-flame-retardant-tdcpp-on-normal-human-corneal-epithelial-cells-implications-for-human-health
#7
Ping Xiang, Rong-Yan Liu, Chao Li, Peng Gao, Xin-Yi Cui, Lena Q Ma
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC50 at 202 μg/mL...
June 19, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28640859/toxic-effects-of-atrazine-on-porcine-oocytes-and-possible-mechanisms-of-action
#8
Bao Yuan, Shuang Liang, Yong-Xun Jin, Ming-Jun Zhang, Jia-Bao Zhang, Nam-Hyung Kim
Because atrazine is a widely used herbicide, its adverse effects on the reproductive system have been extensively researched. In this study, we investigated the effects of atrazine exposure on porcine oocyte maturation and the possible mechanisms. Our results showed that the rates of oocyte maturation significantly decreased after treatment with 200 μM atrazine in vitro. Atrazine treatment resulted in abnormal spindle morphology but did not affect actin distribution. Atrazine exposure not only triggered a DNA damage response but also decreased MPF levels in porcine oocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28640253/a-role-for-tspo-in-mitochondrial-ca-2-homeostasis-and-redox-stress-signaling
#9
Jemma Gatliff, Daniel A East, Aarti Singh, Maria Soledad Alvarez, Michele Frison, Ivana Matic, Caterina Ferraina, Natalie Sampson, Federico Turkheimer, Michelangelo Campanella
The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca(2+) signaling leading to a parallel increase in the cytosolic Ca(2+) pools that activate the Ca(2+)-dependent NADPH oxidase (NOX) thereby increasing ROS...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28640223/non-targeted-metabolomics-analysis-of-the-effects-of-tyrosine-kinase-inhibitors-sunitinib-and-erlotinib-on-heart-muscle-liver-and-serum-metabolism-in-vivo
#10
Brian C Jensen, Traci L Parry, Wei Huang, Amro Ilaiwy, James R Bain, Michael J Muehlbauer, Sara K O'Neal, Cam Patterson, Gary L Johnson, Monte S Willis
Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR), whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR).TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities...
June 22, 2017: Metabolites
https://www.readbyqxmd.com/read/28639957/pulmonary-arterial-hypertension-induced-by-tyrosine-kinase-inhibitors
#11
Jason Weatherald, Marie-Camille Chaumais, David Montani
PURPOSE OF REVIEW: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of several neoplastic conditions; however, pulmonary arterial hypertension (PAH) has been reported as a complication of TKIs, predominantly with dasatinib. Recent studies have elucidated the potential mechanisms of TKI-induced PAH and have better clarified the long-term outcomes. RECENT FINDINGS: In addition to the known association between dasatinib and PAH, several other TKIs have recently been reported to cause PAH, including ponatinib, bosutinib and lapatinib...
July 20, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28639457/glyoxal-toxicity-in-isolated-rat-liver-mitochondria
#12
M Goudarzi, H Kalantari, M Rezaei
Glyoxal is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose, and degradation of glycated proteins. Glyoxal has been linked to oxidative stress and can cause a number of cellular damages, including covalent modification of amino and thiol groups of proteins to form advanced glycation end products. However, the mechanism of glyoxal toxicity has not been fully understood. In this study, we have focused on glyoxal toxicity in isolated rat liver mitochondria...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28638907/ruthenium-ii-p-cymene-complexes-of-a-benzimidazole-based-ligand-capable-of-vegfr2-inhibition-hydrolysis-reactivity-and-cytotoxicity-studies
#13
Sudipta Bhattacharyya, Kallol Purkait, Arindam Mukherjee
The design of Ru or other metal-based anticancer agents may achieve better and faster optimization if the ligands used are also designed to have standalone functions. In this scenario, even after dissociation from the metal complex under adverse conditions, the ligand would have anti-cancer properties. In our work, we have generated a bispyrazole-containing benzimidazole ligand with potency against vascular endothelial growth factor receptor 2 (VEGFR2), which is known to have roles in vasculogenesis/angiogenesis...
June 22, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28638596/environmental-insults-critical-triggers-for-amyotrophic-lateral-sclerosis
#14
REVIEW
Bing Yu, Roger Pamphlett
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a rapid loss of lower and upper motor neurons. As a complex disease, the ageing process and complicated gene-environment interactions are involved in the majority of cases. MAIN BODY: Significant advances have been made in unravelling the genetic susceptibility to ALS with massively parallel sequencing technologies, while environmental insults remain a suspected but largely unexplored source of risk...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28633139/mitochondrial-metabolism-in-a-large-animal-model-of-huntington-disease-the-hunt-for-biomarkers-in-the-spermatozoa-of-presymptomatic-minipigs
#15
Jana Krizova, Hana Stufkova, Marie Rodinova, Monika Macakova, Bozena Bohuslavova, Daniela Vidinska, Jiri Klima, Zdenka Ellederova, Antonin Pavlok, David S Howland, Jiri Zeman, Jan Motlik, Hana Hansikova
BACKGROUND: Huntington disease (HD) is a fatal neurodegenerative disorder involving reduced muscle coordination, mental and behavioral changes, and testicular degeneration. In order to further clarify the decreased fertility and penetration ability of the spermatozoa of transgenic HD minipig boars (TgHD), we applied a set of mitochondrial metabolism (MM) parameter measurements to this promising biological material, which can be collected noninvasively in longitudinal studies. OBJECTIVE: We aimed to optimize methods for MM measurements in spermatozoa and to establish possible biomarkers of HD in TgHD spermatozoa expressing the N-terminal part of mutated human huntingtin...
June 21, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28631341/evaluation-of-flubendiamide-induced-mitochondrial-dysfunction-and-metabolic-changes-in-helicoverpa-armigera-hubner
#16
Bharat Nareshkumar, Shaik Mohammad Akbar, Hari Chand Sharma, Senigala K Jayalakshmi, Kuruba Sreeramulu
Phthalic acid diamide insecticides are the most effective insecticides used against most of the lepidopteran pests including Helicoverpa armigera, a polyphagous pest posing threat to several crops worldwide. The present studies were undertaken to understand different target sites and their interaction with insect ryanodine receptors (RyR). Bioassays indicated that flubendiamide inhibited the larval growth in dose-dependent manner with LD50 value of 0.72 μM, and at 0.8 μM larval growth decreased by about 88%...
June 20, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28630416/hif-1-mediated-suppression-of-mitochondria-electron-transport-chain-function-confers-resistance-to-lidocaine-induced-cell-death
#17
Akihisa Okamoto, Chisato Sumi, Hiromasa Tanaka, Munenori Kusunoki, Teppei Iwai, Kenichiro Nishi, Yoshiyuki Matsuo, Hiroshi Harada, Keizo Takenaga, Hidemasa Bono, Kiichi Hirota
The local anesthetic lidocaine induces cell death by altering reactive oxygen species (ROS) generation and mitochondrial electron transport chain function. Because hypoxia-inducible factor 1 (HIF-1) is involved in determining oxygen metabolism and mitochondria function, we investigated the involvement of HIF-1 activity in lidocaine-induced cell death. We investigated the role of HIF activation on lidocaine-induced caspase activation and cell death in renal cell-derived RCC4 cells lacking functional von Hippel-Lindau (VHL) protein...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628137/-antagonistic-effect-of-quercetin-on-pm2-5-toxicity-in-the-rat-s-embryonic-development-in-vitro
#18
A Q Fan, J Q Feng, W Liu, M J Zhang, T Liu, Y L Zhou, Y J Xu
OBJECTIVE: To explore the antagonistic effect of quercetin on fine particulate matter (PM2.5)-induced embryonic developmental toxicity in vitro. METHODS: PM2.5 was collected on glass fiber filters by PM2.5 samplers during the heating period of Dec. 2015 to Mar. 2016 in an area of Haidian District, Beijing City. The sampled filters were cut into 1 cm×3 cm pieces followed by sonication. The PM2.5 suspension was filtered into a 10 cm glass dish through 8 layers of sterile carbasus and stored at -80 °C until freeze drying...
June 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28627624/pro-oxidant-activity-of-sulforaphane-and-cisplatin-potentiates-apoptosis-and-simultaneously-promotes-autophagy-in-malignant-mesothelioma-cells
#19
Yoon-Jin Lee, Sang-Han Lee
Sulforaphane (SFN) is an isothiocyanate compound derived from glucoraphanin, which is found in cruciferous vegetables, and has been heralded as a chemopreventive and/or chemotherapeutic agent. The present study investigated the effects of SFN on enhancing the anticancer role of cisplatin (cis-dichlorodiammineplatinum; CDDP) in H‑28 malignant mesothelioma cells. At concentrations demonstrating limited toxicity in MeT‑5A normal human mesothelial cells, combination treatment with the two compounds exhibited synergistic growth‑inhibiting and apoptosis‑promoting activities, as demonstrated by a series of proapoptotic events, including reactive oxygen species accumulation, loss of mitochondrial membrane potential, upregulation of p53 expression, increased B‑cell lymphoma 2 (Bcl‑2) associated X protein/Bcl‑2 ratio, activation of caspase‑3, the occurrence of a sub‑G0/G1 peak and an increase in cells with pyknotic and fragmented nuclei, Annexin V‑phycoerythrin‑positive staining and G2/M phase‑transition delay in the cell cycle...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627468/a-novel-chalcone-derivative-lqfm064-induces-breast-cancer-cells-death-via-p53-p21-kit-and-pdgfra
#20
Bruna Lannuce Silva Cabral, Artur Christian Garcia da Silva, Renato Ivan de Ávila, Alane Pereira Cortez, Rangel Magalhães Luzin, Luciano Morais Lião, Eric de Souza Gil, Gérman Sanz, Boniek G Vaz, José R Sabino, Ricardo Menegatti, Marize Campos Valadares
This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC50=21μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor...
June 13, 2017: European Journal of Pharmaceutical Sciences
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