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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#1
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28718725/ellagic-acid-enhances-apoptotic-sensitivity-of-breast-cancer-cells-to-%C3%AE-radiation
#2
Vidhula Ahire, Amit Kumar, Kaushala Prasad Mishra, Gauri Kulkarni
Herbal polyphenols have gained increased significance because of the promises they hold in the prevention and treatment of cancer. There exists an enormous opportunity for the screening and valuation of natural dietary compounds in the development of an effective chemopreventive drug and radiosensitizer that may be of practical use for patients undergoing cancer therapy. This study describes the effect of the flavonoid ellagic acid (EA) on gamma-irradiated human breast cancer MCF-7 cells in vitro when administered alone or in combination with radiation...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28717105/ephedrine-induced-mitophagy-via-oxidative-stress-in-human-hepatic-stellate-cells
#3
Ah Young Lee, Yoonjeong Jang, Seong-Ho Hong, Seung-Hee Chang, Sungjin Park, Sanghwa Kim, Kyung-Sun Kang, Ji-Eun Kim, Myung-Haing Cho
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28716495/3-5-bis-3-dimethylaminomethyl-4-hydroxybenzylidene-4-piperidone-and-related-compounds-induce-glutathione-oxidation-and-mitochondria-mediated-cell-death-in-hct-116-colon-cancer-cells
#4
Eshwari Addala, Hossein Rafiei, Swagatika Das, Brian Bandy, Umashankar Das, Subhas S Karki, Jonathan R Dimmock
This study aims at investigating the cytotoxicity and some of the modes of action of 3,5-bis(3-dimethylamino-4-hydroxybenzylidene)-4-piperidone trihydrochloride 3 and two related compounds 2 (which lacks the dimethylaminomethyl groups) and 4 (which has an additional dimethylaminoethyl substituent in both aryl rings) in order to ascertain the contribution of dimethylaminoethyl substituent to bioactivity. The bioactivities of 2-4 were compared with curcumin 5. Both 2 and 3 displayed submicromolar GI50 values towards HCT-116 cells and were significantly more potent than 4, 5 and 5-fluorouracil (5-FU)...
July 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28715773/developmental-toxicity-of-fe3o4-nanoparticles-on-cysts-and-three-larval-stages-of-artemia-salina
#5
Song Zhu, Ming-Yang Xue, Fei Luo, Wei-Chao Chen, Bin Zhu, Gao-Xue Wang
Using Artemia salina cysts (capsulated and decapsulated) and larvae (instar I, II and III) as experimental models, the potential effects of Fe3O4 nanoparticles (Fe3O4-NPs) on marine ecosystems were investigated. Hatchability, mortality and a number of ethological, morphological and biochemical parameters were selected as end-points to define the toxic responses. Data showed that the hatching rates of capsulated and decapsulated cysts were significantly decreased (p < 0.01) following exposure to 600 mg/L for 24 and 36 h...
July 14, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28715630/misfolded-sod1-accumulation-and-mitochondrial-association-contribute-to-the-selective-vulnerability-of-motor-neurons-in-familial-als-correlation-to-human-disease
#6
Salah Abu-Hamad, Joy Kahn, Marcel F Leyton-Jaimes, Jonathan Rosenblatt, Adrian Israelson
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, with a 10% genetic linkage, of which 20% of these cases may be attributed to mutations in superoxide dismutase (SOD1). Specific mutations in SOD1 have been associated with disease duration, which can be highly variable ranging from a life expectancy of three to beyond ten years. SOD1 neurotoxicity has been attributed to aberrant accumulation of misfolded SOD1, which in its soluble form, binds to intracellular organelles disrupting their function, or forms insoluble toxic aggregates...
July 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28714395/five-decades-of-cuprizone-an-updated-model-to-replicate-demyelinating-diseases
#7
Jose M Vega-Riquer, Gerardo Mendez-Victoriano, Raul A Morales-Luckie, Oscar Gonzalez-Perez
Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropathy and others comprise a group of demyelinating diseases characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter of the brain. To date, the etiology of these disorders is not well known and no effective treatments are currently available. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiology of these diseases...
July 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28711978/the-activity-of-the-antioxidant-defense-system-of-the-weed-species-senna-obtusifolia-l-and-its-resistance-to-allelochemical-stress
#8
Érica Marusa Pergo Coelho, Mauro Cezar Barbosa, Márcio Shigueaki Mito, Gislaine Cristiane Mantovanelli, Rubem Silvério Oliveira, Emy Luiza Ishii-Iwamoto
Senna obtusifolia L., a common weed in the tropical and subtropical regions of the world, is able to germinate under adverse environmental conditions, suggesting that this species has efficient stress-adaptation strategies. The aims of the present work were to examine the energy metabolism and the antioxidant defense system of the Senna obtusifolia L. during seed germination and initial growth, and the responses to allelochemical-induced stress. Respiratory activity, the activities of alcohol dehydrogenase (ADH), superoxide dismutase (SOD), catalase (CAT),guaicol peroxidase (POD), ascorbate peroxidase (APX), glutathione reductase (GR), lipoxygenase (LOX) and the content of malondialdehyde (MDA) and glutathione (GSSG and GSH) were measured...
July 15, 2017: Journal of Chemical Ecology
https://www.readbyqxmd.com/read/28707481/protective-effects-of-melatonin-and-memantine-in-human-retinal-pigment-epithelium-arpe-19-cells-against-2-ethylpyridine-induced-oxidative-stress-implications-for-age-related-macular-degeneration
#9
Handan Bardak, Abdülhadi Cihangir Uğuz, Yavuz Bardak
PURPOSE: To investigate the possible protective effects of melatonin and memantine (MMT) against 2-ethylpyridine (2-EP)-induced oxidative stress and mitochondrial dysfunction in human RPE (ARPE-19) cells in vitro. MATERIALS AND METHODS: The ARPE-19 cells were divided into seven groups. Oxidative stress was triggered by incubating the ARPE-19 cells with 30 µM of 2-EP for 24 hours. Then, 200 µM of melatonin was administered over three days and 20 µM of MMT over six hours prior to the experiment...
July 14, 2017: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/28707237/selenium-protects-against-cadmium-induced-kidney-apoptosis-in-chickens-by-activating-the-pi3k-akt-bcl-2-signaling-pathway
#10
Rong-Kun Bao, Shu-Fang Zheng, Xin-Yue Wang
Cadmium (Cd) is a toxic heavy metal that can induce apoptosis. Selenium (Se) is a necessary trace element and can antagonize the toxicity of many heavy metals, including Cd. PI3K/AKT/Bcl-2 is a key survival signaling pathway that regulates cellular defense system against oxidative injury as well as cell proliferation, survival, and apoptosis. The antagonistic effects of Se on Cd-induced toxicity have been reported. However, little is known about the effect of Se on Cd-induced apoptosis in chicken kidneys via the PI3K/AKT/Bcl-2 signaling pathway...
July 13, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28706150/potential-genotoxic-and-cytotoxicity-of-emamectin-benzoate-in-human-normal-liver-cells
#11
Zhijie Zhang, Xinyu Zhao, Xiaosong Qin
Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705827/3-hydroxyisobutyrate-dehydrogenase-is-involved-in-valine-and-isoleucine-degradation-in-a-thaliana
#12
Peter Schertl, Lennart Danne, Hans-Peter Braun
In plants, amino acid catabolism is especially relevant at metabolic stress situations, e.g. limited carbohydrate availability during extended darkness. Under these conditions, amino acids are used as alternative substrates for respiration. Complete oxidation of the branched chain amino acids (BCAAs) Leucine, Isoleucine and Valine in the mitochondria efficiently allows formation of ATP by oxidative phosphorylation. However, the metabolic pathways for BCAA breakdown are largely unknown so far in plants. A systematic search for Arabidopsis genes encoding proteins resembling enzymes involved in BCAA catabolism in animals, fungi and bacteria as well as proteomic analyses of mitochondrial fractions from Arabidopsis allowed identification of a putative 3-Hydroxyisobutyrate dehydrogenase, AtHDH1 (At4g20930), involved in Valine degradation...
July 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28705594/induction-of-abcg2-bcrp-restricts-the-distribution-of-zidovudine-to-the-fetal-brain-in-rats
#13
María Fernanda Filia, Timoteo Marchini, Juan Mauricio Minoia, Martín Ignacio Roma, Fernanda Teresa De Fino, Modesto Carlos Rubio, Guillermo J Copello, Pablo A Evelson, Roxana Noemí Peroni
Safety concerns for fetus development of zidovudine (AZT) administration as prophylaxis of vertical transmission of HIV persist. We evaluated the participation of the ATP-binding cassette efflux transporter ABCG2 in the penetration of AZT into the fetal brain and the relevance for drug safety. Oral daily doses of AZT (60mg/kg body weight) or its vehicle were administered between post gestational days 11 (E11) and 20 (E20) to Sprague-Dawley pregnant rats. At E21, animals received an intravenous bolus of 60mg AZT/kg body weight in the presence or absence of the ABCG2 inhibitor gefitinib (20mg/kg body weight, ip) and AZT in maternal plasma and fetal brain were measured by HPLC-UV...
July 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28704444/maternal-inheritance-of-deltamethrin-resistance-in-the-salmon-louse-lepeophtheirus-salmonis-kr%C3%A3-yer-is-associated-with-unique-mtdna-haplotypes
#14
Greta Carmona-Antoñanzas, Michaël Bekaert, Joseph L Humble, Sally Boyd, William Roy, David I Bassett, Ross D Houston, Karim Gharbi, James E Bron, Armin Sturm
Parasitic infections by the salmon louse, Lepeophtheirus salmonis (Krøyer), cause huge economic damage in salmon farming in the northern hemisphere, with combined treatment costs and production losses in 2014 having been estimated at US$ 350 million for Norway (annual production 1.25 million tonnes). The control of L. salmonis relies significantly on medicinal treatments, supplemented by non-pharmacological approaches. However, efficacy losses have been reported for several delousing agents, including the pyrethroid deltamethrin...
2017: PloS One
https://www.readbyqxmd.com/read/28701513/the-prion-protein-regulates-glutamate-mediated-ca-2-entry-and-mitochondrial-ca-2-accumulation-in-neurons
#15
Agnese De Mario, Caterina Peggion, Maria Lina Massimino, Francesca Viviani, Angela Castellani, Marta Giacomello, Dmitry Lim, Alessandro Bertoli, Maria Catia Sorgato
The prion protein, PrP(C), whose conformational misfolding originates deadly prions, has a still unclarified cellular function despite decades of intensive research. Following our recent finding that PrP(C) limits Ca(2+) entry via store-operated Ca(2+) channels in neurons, we investigated whether the protein could also control the activity of ionotropic glutamate receptors (iGluRs). To this end, we compared local Ca(2+) movements in primary cerebellar granule neurons and cortical neurons, expressing, or not, PrP(C), transduced with genetically encoded Ca(2+) probes...
July 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28700943/a-role-for-mitochondrial-translation-in-promotion-of-viability-in-k-ras-mutant-cells
#16
Timothy D Martin, Danielle R Cook, Mei Yuk Choi, Mamie Z Li, Kevin M Haigis, Stephen J Elledge
Activating mutations in the KRAS oncogene are highly prevalent in tumors, especially those of the colon, lung, and pancreas. To better understand the genetic dependencies that K-Ras mutant cells rely upon for their growth, we employed whole-genome CRISPR loss-of-function screens in two isogenic pairs of cell lines. Since loss of essential genes is uniformly toxic in CRISPR-based screens, we also developed a small hairpin RNA (shRNA) library targeting essential genes. These approaches uncovered a large set of proteins whose loss results in the selective reduction of K-Ras mutant cell growth...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28700655/cyclophosphamide-leads-to-persistent-deficits-in-physical-performance-and-in-vivo-mitochondria-function-in-a-mouse-model-of-chemotherapy-late-effects
#17
Marie-Laure Crouch, Gary Knowels, Rudolph Stuppard, Nolan G Ericson, Jason H Bielas, David J Marcinek, Karen L Syrjala
Fatigue is the symptom most commonly reported by long-term cancer survivors and is increasingly recognized as related to skeletal muscle dysfunction. Traditional chemotherapeutic agents can cause acute toxicities including cardiac and skeletal myopathies. To investigate the mechanism by which chemotherapy may lead to persistent skeletal muscle dysfunction, mature adult mice were injected with a single cyclophosphamide dose and evaluated for 6 weeks. We found that exposed mice developed a persistent decrease in treadmill running time compared to baseline (25...
2017: PloS One
https://www.readbyqxmd.com/read/28698968/inhibition-of-poly-adp-ribose-polymerase-1-enhances-gene-expression-of-selected-sirtuins-and-app-cleaving-enzymes-in-amyloid-beta-cytotoxicity
#18
Przemysław L Wencel, Walter J Lukiw, Joanna B Strosznajder, Robert Piotr Strosznajder
Poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs) are involved in the regulation of cell metabolism, transcription, and DNA repair. Alterations of these enzymes may play a crucial role in Alzheimer's disease (AD). Our previous results indicated that amyloid beta (Aβ) peptides and inflammation led to activation of PARP1 and cell death. This study focused on a role of PARP1 in the regulation of gene expression for SIRTs and beta-amyloid precursor protein (βAPP) cleaving enzymes under Aβ42 oligomers (AβO) toxicity in pheochromocytoma cells (PC12) in culture...
July 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28698525/hepatoprotective-role-of-hydrangea-macrophylla-against-sodium-arsenite-induced-mitochondrial-dependent-oxidative-stress-via-the-inhibition-of-mapk-caspase-3-pathways
#19
Md Rashedunnabi Akanda, Hyun-Jin Tae, In-Shik Kim, Dongchoon Ahn, Weishun Tian, Anowarul Islam, Hyeon-Hwa Nam, Byung-Kil Choo, Byung-Yong Park
Sodium arsenite (NaAsO₂) has been recognized as a worldwide health concern. Hydrangea macrophylla (HM) is used as traditional Chinese medicine possessing antioxidant activities. The study was performed to investigate the therapeutic role and underlying molecular mechanism of HM on NaAsO₂-induced toxicity in human liver cancer (HepG2) cells and liver in mice. The hepatoprotective role of HM in HepG2 cells was assessed by using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and lactate dehydrogenase (LDH) assays...
July 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28697680/t-2-toxin-induces-apoptosis-via-the-bax-dependent-caspase-3-activation-in-mouse-primary-leydig-cells
#20
Yong Fa Zhang, Pan Ke Su, Lun Ji Wang, Hui Qi Zheng, Xue Fei Bai, Ping Li, Xiang Ping Meng, Jian Ying Yang
To explore the toxic effect of T-2 toxin on mouse Leydig cells and its underlying molecular mechanisms, we isolated Leydig cells from mature mice, set-up Leydig cells culture, treated cells with T-2 toxin, evaluated cell proliferation, detected the caspase-3 activity, mitochondrial activity and apoptosis rate, and measured the mRNA levels of Bcl-2, Bax, PARP and caspase-3. T-2 toxin inhibited cell proliferation at concentrations higher than 10(-9) M or time more than 12 h, T-2 toxin also decreased Bcl-2 expression at the mRNA levels and mitochondrial activity at concentrations higher than 10(-9) M...
July 11, 2017: Toxicology Mechanisms and Methods
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