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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/28098219/combined-lrrk2-mutation-aging-and-chronic-low-dose-oral-rotenone-as-a-model-of-parkinson-s-disease
#1
Hui-Fang Liu, Philip Wing-Lok Ho, Gideon Chi-Ting Leung, Colin Siu-Chi Lam, Shirley Yin-Yu Pang, Lingfei Li, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity. Here, we explored the interplay amongst these factors using mutant LRRK2(R1441G) (leucine-rich-repeat-kinase-2) knockin mice. We found that mutant primary cortical and mesencephalic dopaminergic neurons were more susceptible to rotenone-induced ATP deficiency and cell death...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097511/brain-calcification-and-movement-disorders
#2
REVIEW
Vladimir S Kostić, Igor N Petrović
Brain calcifications may be an incidental finding on neuroimaging in normal, particularly older individuals, but can also indicate numerous hereditary and nonhereditary syndromes, and metabolic, environmental, infectious, autoimmune, mitochondrial, traumatic, or toxic disorders. Bilateral calcifications most commonly affecting the basal ganglia may often be found in idiopathic cases, and a new term, primary familial brain calcification (PFBC), has been proposed that recognizes the genetic causes of the disorder and that calcifications occurred well beyond the basal ganglia...
January 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28097102/mechanisms-of-accelerated-liver-fibrosis-progression-during-hiv-infection
#3
REVIEW
Jose D Debes, Paul R Bohjanen, Andre Boonstra
With the introduction of antiretroviral therapy (ART), a dramatic reduction in HIV-related morbidity and mortality has been observed. However, it is now becoming increasingly clear that liver-related complications, particularly rapid fibrosis development from ART as well as from the chronic HIV infection itself, are of serious concern to HIV patients. The pathophysiology of liver fibrosis in patients with HIV is a multifactorial process whereby persistent viral replication, and bacterial translocation lead to chronic immune activation and inflammation, which ART is unable to fully suppress, promoting production of fibrinogenic mediators and fibrosis...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28094496/chemoproteomic-profiling-of-acetanilide-herbicides-reveals-their-role-in-inhibiting-fatty-acid-oxidation
#4
Jessica L Counihan, Megan Duckering, Esha Dalvie, Wan-Min Ku, Leslie A Bateman, Karl J Fisher, Daniel K Nomura
Acetanilide herbicides are among the most widely used pesticides in the United States, but their toxicological potential and mechanisms remain poorly understood. Here, we have used chemoproteomic platforms to map proteome-wide cysteine reactivity of acetochlor (AC), the most widely used acetanilide herbicide, in vivo in mice. We show that AC directly reacts with >20 protein targets in vivo in mouse liver, including the catalytic cysteines of several thiolase enzymes involved in mitochondrial and peroxisomal fatty acid oxidation...
January 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28092019/urb597-and-the-cannabinoid-win55-212-2-reduce-behavioral-and-neurochemical-deficits-induced-by-mptp-in-mice-possible-role-of-redox-modulation-and-nmda-receptors
#5
Angel Escamilla-Ramírez, Esperanza García, Guadalupe Palencia-Hernández, Ana Laura Colín-González, Sonia Galván-Arzate, Isaac Túnez, Julio Sotelo, Abel Santamaría
Several physiological events in the brain are regulated by the endocannabinoid system (ECS). While synthetic cannabinoid receptor (CBr) agonists such as WIN55,212-2 act directly on CBr, agents like URB597, a fatty acid amide hydrolase (FAAH) inhibitor, induce a more "physiological" activation of CBr by increasing the endogenous levels of the endocannabinoid anandamide (AEA). Herein, we compared the pre- and post-treatment efficacy of URB597 and WIN55,212-2 on different endpoints evaluated in the toxic model produced by the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice...
January 14, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28090784/effect-of-resveratrol-and-tetracycline-on-the-subacute-paraquat-toxicity-in-mice
#6
R M Satpute, P P Pawar, S Puttewar, S D Sawale, P D Ambhore
Paraquat (PQ) is a nonselective bipyridyl herbicide widely used in agriculture to control weeds, but its accidental, occupational, or intentional exposure in humans is known to cause pneumo- and neurotoxicity which may proves fatal. Oxidative stress is reported as an underlined mechanism of PQ-induced toxicity in alveolar cells, neurons, and astroglia. PQ generates superoxides both through electron transport reaction (ETC) with nicotinamide adenine dinucleotide-dependent oxidoreductase and by the redox cycling via reaction with molecular oxygen...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28089588/discovery-of-a-novel-series-of-n-hydroxypyridone-derivatives-protecting-astrocytes-against-hydrogen-peroxide-induced-toxicity-via-improved-mitochondrial-functionality
#7
Sarbjit Singh, Ja-Il Goo, Hyojin Noh, Sung Jae Lee, Myoung Woo Kim, Hyejun Park, Hitesh B Jalani, Kyeong Lee, Chunsook Kim, Won-Ki Kim, Chung Ju, Yongseok Choi
Astrocytes play a key role in brain homeostasis, protecting neurons against neurotoxic stimuli such as oxidative stress. Therefore, the neuroprotective therapeutics that enhance astrocytic functionality has been regarded as a promising strategy to reduce brain damage. We previously reported that ciclopirox, a well-known antifungal N-hydroxypyridone compound, protects astrocytes from oxidative stress by enhancing mitochondrial function. Using the N-hydroxypyridone scaffold, we have synthesized a series of cytoprotective derivatives...
January 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28088732/apelin-13-protects-rat-primary-cortical-glia-neuron-co-culture-against-pentylenetetrazole-induced-toxicity
#8
Taj Pari Kalantaripour, Saeed Esmaeili-Mahani, Vahid Sheibani, Hamid Najafipour, Majid Asadi-Shekaari M
In spite of recent advances in the treatment of epilepsy, up to 35% of people living with the condition do not respond to accessible anti-epileptic drugs (AEDs) and continue to experience regular, devastating and potentially life-threatening seizures. Neuronal death is a significant feature of epilepsy in humans and experimental models. It has been reported that apelin, an endogenous ligand for the angiotensin-1-like receptor (APJ), has anticonvulsive as well as protective effects in some neurodegenerative situations...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088622/reactive-oxygen-species-and-cancer-paradox-to-promote-or-to-suppress
#9
REVIEW
Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088493/apoptosis-induced-by-the-methanol-extract-of-salvia-miltiorrhiza-bunge-in-non-small-cell-lung-cancer-through-pten-mediated-inhibition-of-pi3k-akt-pathway
#10
Yin-Tao Ye, Wei Zhong, Pei Sun, Dong Wang, Chen Wang, Li-Min Hu, Jun-Qiang Qian
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies have reported that the active component tanshinones displayed a variety of biological activities: antithrombous, antiplatelet aggregation, antioxidant and antitumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28086830/sigma-2-receptor-agonist-derivatives-of-1-cyclohexyl-4-3-5-methoxy-1-2-3-4-tetrahydronaphthalen-1-yl-propyl-piperazine-pb28-induce-cell-death-via-mitochondrial-superoxide-production-and-caspase-activation-in-pancreatic-cancer
#11
Maria Laura Pati, John R Hornick, Mauro Niso, Francesco Berardi, Dirk Spitzer, Carmen Abate, William Hawkins
BACKGROUND: Despite considerable efforts by scientific research, pancreatic cancer is the fourth leading cause of cancer related mortalities. Sigma-2 receptors, which are overexpressed in several tumors, represent promising targets for triggering selective pancreatic cancer cells death. METHODS: We selected five differently structured high-affinity sigma-2 ligands (PB28, PB183, PB221, F281 and PB282) to study how they affect the viability of diverse pancreatic cancer cells (human cell lines BxPC3, AsPC1, Mia PaCa-2, and Panc1 and mouse Panc-02, KCKO and KP-02) and how this is reflected in vivo in a tumor model...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28079261/effect-of-parthanatos-on-ropivacaine-induced-damage-in-sh-sy5y-cells
#12
Ting Zheng, Chun-Ying Zheng, Xiao-Chun Zheng, Ruo-Guang Zhao, Yan-Qing Chen
Ropivacaine is one of the most common but toxic local anesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and NAD(+) depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD(+) level, and Western blots were used to analyze the expression levels of PARP-1 and AIF after ropivacaine treatments with different concentrations and durations...
January 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28079192/differential-cytotoxic-effects-of-graphene-and-graphene-oxide-on-skin-keratinocytes
#13
Marco Pelin, Laura Fusco, Verónica León, Cristina Martín, Alejandro Criado, Silvio Sosa, Ester Vázquez, Aurelia Tubaro, Maurizio Prato
Impressive properties make graphene-based materials (GBMs) promising tools for nanoelectronics and biomedicine. However, safety concerns need to be cleared before mass production of GBMs starts. As skin, together with lungs, displays the highest exposure to GBMs, it is of fundamental importance to understand what happens when GBMs get in contact with skin cells. The present study was carried out on HaCaT keratinocytes, an in vitro model of skin toxicity, on which the effects of four GBMs were evaluated: a few layer graphene, prepared by ball-milling treatment (FLG), and three samples of graphene oxide (GOs, a research-grade GO1, and two commercial GOs, GO2 and GO3)...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079002/neurotoxicity-associated-with-platinum-based-anti-cancer-agents-what-are-the-implications-of-copper-transporters
#14
Vanesa Stojanovska, Rachel McQuade, Emma Rybalka, Kulmira Nurgali
Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of interstrand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dorsal root ganglia neurons. Although all platinum-based agents form similar DNA adducts, they are quite different in terms of activation, systemic toxicity and tolerance...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28078787/targeting-nasopharyngeal-carcinoma-by-artesunate-through-inhibiting-akt-mtor-and-inducing-oxidative-stress
#15
Qin Li, Wei Ni, Zhifeng Deng, Minghe Liu, Lazhi She, Qiong Xie
Drug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase-dependent and mitochondria-independent pathways in multiple NPC cell lines...
January 11, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28078681/synthesis-and-stability-studies-of-ga-67-labeled-phosphonium-salts
#16
Mingyue Kardashinsky, Nigel Lengkeek, Louis M Rendina
Delocalized lipophilic cations such as tri- and tetra-arylphosphonium are able to diffuse across the mitochondrial membrane, which allows them to selectively accumulate in cells with a high transmembrane potential (ΔΨm ). The mitochondrial membrane potential of cancer cells and cardiomyocytes has been reported to be significantly higher than that of normal epithelial cells. This feature can be exploited for the selective accumulation of phosphonium derivatives for the purposes of molecular imaging using radionuclides...
January 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#17
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28073829/dutpase-dut-is-mutated-in-a-novel-monogenic-syndrome-with-diabetes-and-bone-marrow-failure
#18
Reinaldo Sousa Dos Santos, Mathilde Daures, Anne Philippi, Sophie Romero, Lorella Marselli, Piero Marchetti, Valérie Senée, Delphine Bacq, Céline Besse, Baz Baz, Laura Marroquí, Sarah Ivanoff, Julien Masliah-Planchon, Marc Nicolino, Jean Soulier, Gérard Socié, Decio L Eizirik, Jean-François Gautier, Cécile Julier
We describe a new syndrome characterized by early onset diabetes mellitus, associated with bone marrow failure affecting mostly the erythrocytic lineage. Using whole exome sequencing in a remotely consanguineous patient from a family with two affected siblings, we identified a single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene (NCBI Gene ID: 1854), affecting both the mitochondrial (DUT-M p.Y142C) and the nuclear (DUT-N p.Y54C) isoforms. We found the same homozygous mutation in an unrelated consanguineous patient with diabetes and bone marrow aplasia from a family with two affected siblings, while none of the >60,000 subjects from the Exome Aggregation Consortium (ExAC) was homozygous for this mutation...
January 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28073120/nano-pelargonidin-protects-hyperglycemic-induced-l6-cells-against-mitochondrial-dysfunction
#19
Asmita Samadder, Debojyoti Tarafdar, Suresh K Abraham, Kumaresh Ghosh, Anisur Rahman Khuda-Bukhsh
Nano-encapsulation of several natural products has become an important tool in enhancing the bioavailability of some modern drugs against many diseases. Pelargonidin is an anthocyanidin found in many fruits and vegetables. Pelargonidin is loaded with poly-lactide-co-glycolic-acid, a non-toxic biodegradable polymer, to produce nano-pelargonidin. Size, morphology, zeta potential, and planar uniformity of formulated nano-pelargonidin were determined by atomic force microscopy and dynamic light scattering. The time required for cellular entry, folds of nano-pelargonidin, and drug encapsulation efficiency of poly-lactide-co-glycolic-acid were also ascertained...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28070799/metabolic-alterations-and-the-protective-effect-of-punicalagin-against-glutamate-induced-oxidative-toxicity-in-ht22-cells
#20
Kavitha Pathakoti, Lavanya Goodla, Manjunath Manubolu, Tewin Tencomnao
Oxidative stress is involved in many neurological diseases, including Alzheimer's disease. Punicalagin (PC) is a hydrolysable polyphenol derived from Punica granatum and a potent antioxidant. In this study, the neuroprotective effect of PC on glutamate-induced oxidative stress was evaluated in the mouse hippocampal cell line, HT22. PC treatment protected HT22 cells from glutamate-induced cell death in a concentration-dependent manner, potentially attenuated glutamate-induced intracellular reactive oxygen species (ROS) and restored the mitochondrial membrane depolarization...
January 9, 2017: Neurotoxicity Research
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