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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/28212938/the-combined-effects-of-3-4-methylenedioxymethamphetamine-mdma-and-selected-substituted-methcathinones-on-measures-of-neurotoxicity
#1
Nicholas B Miner, James P O'Callaghan, Tamara J Phillips, Aaron Janowsky
The rise in popularity of substituted methcathinones (aka "bath salts") has increased the focus on their neurotoxic effects. Two commonly abused methcathinones, 3,4-methylenedioxymethcathinone (methylone, MDMC) and 3,4-methylenedioxypyrovalerone (MDPV), are often concomitantly ingested with the illicit drug 3,4-methylenedioxymethamphetamine (MDMA). To examine potential neurotoxic effects of these drug combinations, C57BL/6J mice were administered 4 i.p. injection of the drugs, at 2h intervals, either singularly: MDMA 15 or 30mg/kg, methylone 20mg/kg, MDPV 1mg/kg; or in combination: methylone/MDMA 20/15mg/kg, MDPV/MDMA 1/15mg/kg...
February 14, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28212849/hydrogen-sulfide-endoplasmic-reticulum-stress-and-alcohol-mediated-neurotoxicity
#2
REVIEW
Akash K George, Jyotirmaya Behera, Kimberly E Kelly, Yuankun Zhai, Neetu Tyagi
Alcohol is one of the most socially accepted addictive drugs in modern society. Its abuse affects virtually all organ systems with the central nervous system (CNS) being particularly vulnerable to excessive alcohol exposure. Alcohol exposure also causes profound damage to both the adult and developing brain. Excessive alcohol consumption induces numerous pathophysiological stress responses, one of which is the endoplasmic reticulum (ER) stress response. Potential mechanisms that trigger the alcohol induced ER stress response are either directly or indirectly related to alcohol metabolism, which include toxic levels of acetaldehyde and homocysteine, oxidative stress and abnormal epigenetic modifications...
February 14, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28203577/ertapenem-induced-encephalopathy-in-a-patient-with-normal-renal-function
#3
S Scott Sutton, Mark Jumper, Sean Cook, Babatunde Edun, Michael D Wyatt
Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem. Encephalopathy is a type of neurotoxicity that is defined as a diffuse disease of the brain that alters brain function or structure. We report a patient with normal renal function who developed ertapenem-induced encephalopathy manifesting as altered mental status, hallucinations, and dystonic symptoms. The patient's symptoms improved dramatically following ertapenem discontinuation, consistent with case reports describing ertapenem neurotoxicity in renal dysfunction...
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28186109/astragali-radix-could-it-be-an-adjuvant-for-oxaliplatin-induced-neuropathy
#4
Lorenzo Di Cesare Mannelli, Alessandra Pacini, Laura Micheli, Angelo Pietro Femia, Mario Maresca, Matteo Zanardelli, Alfredo Vannacci, Eugenia Gallo, Anna Rita Bilia, Giovanna Caderni, Fabio Firenzuoli, Alessandro Mugelli, Carla Ghelardini
Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. In the absence of effective pharmacological compounds, the opportunity to identify safe adjuvant treatments among medicinal plants seems appropriate. Astragali radix is an adaptogenic herbal product recently analyzed in platinum-treated cancer patients. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28178069/montelukast-treatment-protects-nigral-dopaminergic-neurons-against-microglial-activation-in-the-6-hydroxydopamine-mouse-model-of-parkinson-s-disease
#5
Hannah Jang, Sehwan Kim, Jae Man Lee, Yong-Seok Oh, Sang Myun Park, Sang Ryong Kim
Although the main cause of degeneration of the nigrostriatal dopaminergic (DA) projection in Parkinson's disease (PD) is still controversial, many reports suggest that excessive inflammatory responses mediated by activated microglia can induce neurotoxicity in the nigrostriatal DA system in vivo. Montelukast, which plays an anti-inflammatory role, is used to treat patients with asthma. In addition, recent studies have reported that its administration could reduce neuroinflammatory activities, showing beneficial effects against various neuropathological conditions...
February 7, 2017: Neuroreport
https://www.readbyqxmd.com/read/28164768/protective-effect-of-aspirin-against-oligomeric-a%C3%AE-42-induced-mitochondrial-alterations-and-neurotoxicity-in-differentiated-ec-p19-neuronal-cells
#6
Hamendra Singh Parmar, Zbynek Houdek, Martin Pesta, Vaclava Cerna, Pavel Dvorak, Jiri Hatina
Amyloid-beta (Aβ) induced mitochondrial dysfunction is one of the major causes of neuronal toxicity in Alzheimer's disease. Many recent reports suggest involvement of mitochondrial alterations through intracellular accumulation of oligomeric Aβ. These mitochondrial alterations include increased reactive oxygen species (ROS), mt-DNA depletion, decreased oxidative phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc. These all defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28159824/novel-thrombolytic-drug-based-on-thrombin-cleavable-microplasminogen-coupled-to-a-single-chain-antibody-specific-for-activated-gpiib-iiia
#7
Thomas Bonnard, Zachary Tennant, Be'Eri Niego, Ruchi Kanojia, Karen Alt, Shweta Jagdale, Lok Soon Law, Sheena Rigby, Robert Lindsay Medcalf, Karlheinz Peter, Christoph Eugen Hagemeyer
BACKGROUND: Thrombolytic therapy for acute thrombosis is limited by life-threatening side effects such as major bleeding and neurotoxicity. New treatment options with enhanced fibrinolytic potential are therefore required. Here, we report the development of a new thrombolytic molecule that exploits key features of thrombosis. We designed a recombinant microplasminogen modified to be activated by the prothrombotic serine-protease thrombin (HtPlg), fused to an activation-specific anti-glycoprotein IIb/IIIa single-chain antibody (SCE5), thereby hijacking the coagulation system to initiate thrombolysis...
February 3, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28157650/urb597-reduces-biochemical-behavioral-and-morphological-alterations-in-two-neurotoxic-models-in-rats
#8
Marisol Maya-López, Hipolito A Ruiz-Contreras, María de Jesús Negrete-Ruíz, Julián Elías Martínez-Sánchez, Juan Benítez-Valenzuela, Ana Laura Colín-González, Juana Villeda-Hernández, Laura Sánchez-Chapul, Carmen Parra-Cid, Edgar Rangel-López, Abel Santamaría
BACKGROUND: URB597 is a compound largely linked to the inhibition of fatty acid amide hydrolase (FAAH), an enzyme responsible for the metabolic degradation of the endocannabinoid anandamide (AEA). Despite this pharmacological property accounts for its modulatory profile demonstrated in some neurotoxic paradigms, the possible protective properties of this agent have been poorly investigated, and deserve exploration in different neurotoxic models. In this study, we explored the effects of URB597 on oxidative damage to lipids and other major endpoints of toxicity in two neurotoxic models in vivo in rats (the first one produced by the mitochondrial neurotoxin 3-nitropropionic acid [3-NP], and the other generated by the striatal injection of the pro-oxidant toxin 6-hydroxidopamine [6-OHDA]) in order to provide further supporting evidence of its modulatory profile...
January 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28155214/ra-differentiation-enhances-dopaminergic-features-changes-redox-parameters-and-increases-dopamine-transporter-dependency-in-6-hydroxydopamine-induced-neurotoxicity-in-sh-sy5y-cells
#9
Fernanda M Lopes, Leonardo Lisbôa da Motta, Marco A De Bastiani, Bianca Pfaffenseller, Bianca W Aguiar, Luiz F de Souza, Geancarlo Zanatta, Daiani M Vargas, Patrícia Schönhofen, Giovana F Londero, Liana M de Medeiros, Valder N Freire, Alcir L Dafre, Mauro A A Castro, Richard B Parsons, Fabio Klamt
Research on Parkinson's disease (PD) and drug development is hampered by the lack of suitable human in vitro models that simply and accurately recreate the disease conditions. To counteract this, many attempts to differentiate cell lines, such as the human SH-SY5Y neuroblastoma, into dopaminergic neurons have been undertaken since they are easier to cultivate when compared with other cellular models. Here, we characterized neuronal features discriminating undifferentiated and retinoic acid (RA)-differentiated SH-SYSY cells and described significant differences between these cell models in 6-hydroxydopamine (6-OHDA) cytotoxicity...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28145852/safranal-prevents-rotenone-induced-oxidative-stress-and-apoptosis-in-an-in-vitro-model-of-parkinson-s-disease-through-regulating-keap1-nrf2-signaling-pathway
#10
P-K Pan, L-Y Qiao, X-N Wen
Safranal, a major constituent of saffron, possesses antioxidant and anti-apoptotic properties showing considerable neuroprotective effects. However, whether safranal shows therapeutic effect on Parkinson's disease (PD) remains unknown. In this study, we aimed to investigate the potential effect of safranal on PD using an in vitro model of PD induced by rotenone. We found that safranal significantly inhibited rotenone-induced cell death in a dose-dependent manner. Moreover, safranal also markedly suppressed the reactive oxygen species (ROS) generation and cell apoptosis induced by rotenone...
December 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28137608/silymarin-protects-against-acrylamide-induced-neurotoxicity-via-nrf2-signalling-in-pc12-cells
#11
Liang Li, Hong-Yang Sun, Wei Liu, Hong-Yu Zhao, Mei-Li Shao
Silymarin (SM) is a well-known antioxidant, anti-inflammatory and anti-cancer compound extracted from the milk thistle. Here, we investigated the protective effect of SM against acrylamide (AA)-induced neurotoxicity, mainly caused by oxidative stress, via activation of the nuclear transcription factor E2-related factor 2 (Nrf2) signalling pathway in PC12 cells. The MTT reduction assay was used to measure cell viability in various drug-treated groups and demonstrated that SM could increase cell viability in AA-treated PC12 cells...
January 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28134307/fingolimod-limits-acute-a%C3%AE-neurotoxicity-and-promotes-synaptic-versus-extrasynaptic-nmda-receptor-functionality-in-hippocampal-neurons
#12
Pooja Joshi, Martina Gabrielli, Luisa Ponzoni, Silvia Pelucchi, Matteo Stravalaci, Marten Beeg, Sonia Mazzitelli, Daniela Braida, Mariaelvina Sala, Enrica Boda, Annalisa Buffo, Marco Gobbi, Fabrizio Gardoni, Michela Matteoli, Elena Marcello, Claudia Verderio
Fingolimod, also known as FTY720, is an analogue of the sphingolipid sphingosine, which has been proved to be neuroprotective in rodent models of Alzheimer's disease (AD). Several cellular and molecular targets underlying the neuroprotective effects of FTY720 have been recently identified. However, whether the drug directly protects neurons from toxicity of amyloid-beta (Aβ) still remains poorly defined. Using a combination of biochemical assays, live imaging and electrophysiology we demonstrate that FTY720 induces a rapid increase in GLUN2A-containing neuroprotective NMDARs on the surface of dendritic spines in cultured hippocampal neurons...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28131834/7-4-hydroxy-3-methoxyphenyl-1-phenyl-4e-hepten-3-one-alleviates-a%C3%AE-1-42-induced-cytotoxicity-through-pi3k-mtor-pathways
#13
Hanlin Xiao, Qinghua Zhang, Yinghui Peng, Genyun Tang, Yumei Liao, Xiaoji Zhuang, Wen-Cai Ye, Ying Wang, Lei Shi
Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. Increasing evidence has shown that β-amyloid protein (Aβ) production is the key pathological cause of AD. 7-(4-Hydroxy-3-methoxyphenyl)-1-phenyl-4E-hepten-3-one (AO-2), a natural diarylheptanoid, is previously found to have activities in neuronal differentiation and neurite outgrowth, and its analogue shows protective effects against Aβ. In this study, we further investigated the function of AO-2 toward Aβ-induced injuries in PC12 cells and hippocampal neurons...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28130052/pharmacological-activation-of-the-neurotensin-receptor-1-abrogates-the-methamphetamine-induced-striatal-apoptosis-in-the-mouse-brain
#14
Qingkun Liu, Ariela Hazan, Eddie Grinman, Jesus A Angulo
Methamphetamine (METH) is a widely abused psychostimulant displaying potent addictive and neurotoxic properties. METH induces neurotoxicity of dopaminergic terminals and striatal neurons in the striatum. Despite much information on neurotransmitters, the role of neuropeptides is poorly understood. In this study, we investigated the role of the neuropeptide neurotensin on the METH-induced apoptosis of some striatal neurons in mice. We observed that a single injection of METH (30 mg/kg, ip) induced the loss of approximately 15% of striatal neurons...
January 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28127506/chemotherapy-induced-neuropathies-a-growing-problem-for-patients-and-health-care-providers
#15
Marta Banach, Judyta K Juranek, Aneta L Zygulska
INTRODUCTION: Chemotherapy-induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti-cancer drugs are: platinum-based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids...
January 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28125041/synthesis-modelling-and-anticonvulsant-studies-of-new-quinazolines-showing-three-highly-active-compounds-with-low-toxicity-and-high-affinity-to-the-gaba-a-receptor
#16
Mohamed F Zayed, Saleh K Ihmaid, Hany E A Ahmed, Khaled El-Adl, Ahmed M Asiri, Abdelsattar M Omar
Some novel fluorinated quinazolines (5a-j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), (13)C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test...
January 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28124209/nonsteroidal-anti-inflammatory-drugs-attenuate-amyloid-%C3%AE-protein-induced-actin-cytoskeletal-reorganization-through-rho-signaling-modulation
#17
Patricia Ferrera, Angélica Zepeda, Clorinda Arias
Amyloid-β protein (Aβ) neurotoxicity occurs along with the reorganization of the actin-cytoskeleton through the activation of the Rho GTPase pathway. In addition to the classical mode of action of the non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin, and ibuprofen have Rho-inhibiting effects. In order to evaluate the role of the Rho GTPase pathway on Aβ-induced neuronal death and on neuronal morphological modifications in the actin cytoskeleton, we explored the role of NSAIDS in human-differentiated neuroblastoma cells exposed to Aβ...
January 25, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28115709/gleevec-shifts-app-processing-from-a-%C3%AE-cleavage-to-a-nonamyloidogenic-cleavage
#18
William J Netzer, Karima Bettayeb, Subhash C Sinha, Marc Flajolet, Paul Greengard, Victor Bustos
Neurotoxic amyloid-β peptides (Aβ) are major drivers of Alzheimer's disease (AD) and are formed by sequential cleavage of the amyloid precursor protein (APP) by β-secretase (BACE) and γ-secretase. Our previous study showed that the anticancer drug Gleevec lowers Aβ levels through indirect inhibition of γ-secretase activity. Here we report that Gleevec also achieves its Aβ-lowering effects through an additional cellular mechanism. It renders APP less susceptible to proteolysis by BACE without inhibiting BACE enzymatic activity or the processing of other BACE substrates...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28115274/toxicity-of-the-amphetamine-metabolites-4-hydroxyamphetamine-and-4-hydroxynorephedrine-in-human-dopaminergic-differentiated-sh-sy5y-cells
#19
R Feio-Azevedo, V M Costa, L M Ferreira, P S Branco, F C Pereira, M L Bastos, F Carvalho, J P Capela
Amphetamine (AMPH) is a psychostimulant used worldwide by millions of patients in the clinical treatment of attention deficit hyperactivity disorder, narcolepsy or even obesity, and is also a drug of abuse. 4-Hydroxynorephedrine (4-OHNE) and 4-hydroxyamphetamine (4-OHAMPH) are two major metabolites known to persist in the brain longer than AMPH. The contribution of AMPH metabolites for its neurotoxicity is undetermined. We evaluated the toxicity of AMPH and its metabolites 4-OHNE and 4-OHAMPH, obtained by chemical synthesis, in human dopaminergic differentiated SH-SY5Y neurons...
January 20, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28107189/docosahexaenoic-acid-and-disulfiram-act-in-concert-to-kill-cancer-cells-a-mutual-enhancement-of-their-anticancer-actions
#20
Yang Jiao, Bethany N Hannafon, Roy R Zhang, Kar-Ming Fung, Wei-Qun Ding
We previously reported a synergistic anticancer action of clioquinol and docosahexaenoic acid (DHA) in human cancer cells. However, clioquinol has been banned from the clinic due to its neurotoxicity. This study identified disulfiram (DSF) as a substitute compound to clioquinol, acting in concert with DHA to more effectively kill cancer cells and suppress tumor growth. Treatment with DSF and DHA induced greater apoptotic cell death and suppression of tumor growth in vitro and in vivo, as compared to DSF and DHA used alone...
January 17, 2017: Oncotarget
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