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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/28342892/comparison-of-three-cell-based-drug-screening-platforms-for-hsv-1-infection
#1
Leonardo D'Aiuto, Kelly Williamson, Peter Dimitrion, James McNulty, Carla E Brown, Chanti Babu Dokuburra, Alexander J Nielsen, Wen Jing Lin, Paolo Piazza, Mark E Schurdak, Joel Wood, Robert H Yolken, Paul R Kinchington, David C Bloom, Vishwajit L Nimgaonkar
Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS)...
March 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28327181/soluble-oligomeric-amyloid-%C3%AE-induces-calcium-dyshomeostasis-that-precedes-synapse-loss-in-the-living-mouse-brain
#2
Michal Arbel-Ornath, Eloise Hudry, Josiah R Boivin, Tadafumi Hashimoto, Shuko Takeda, Kishore V Kuchibhotla, Steven Hou, Carli R Lattarulo, Arianna M Belcher, Naomi Shakerdge, Pariss B Trujillo, Alona Muzikansky, Rebecca A Betensky, Bradley T Hyman, Brian J Bacskai
BACKGROUND: Amyloid-β oligomers (oAβ) are thought to mediate neurotoxicity in Alzheimer's disease (AD), and previous studies in AD transgenic mice suggest that calcium dysregulation may contribute to these pathological effects. Even though AD mouse models remain a valuable resource to investigate amyloid neurotoxicity, the concomitant presence of soluble Aβ species, fibrillar Aβ, and fragments of amyloid precursor protein (APP) complicate the interpretation of the phenotypes. METHOD: To explore the specific contribution of soluble oligomeric Aβ (oAβ) to calcium dyshomeostasis and synaptic morphological changes, we acutely exposed the healthy mouse brain, at 3 to 6 months of age, to naturally occurring soluble oligomers and investigated their effect on calcium levels using in vivo multiphoton imaging...
March 21, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28323108/chronic-methamphetamine-exposure-significantly-decreases-microglia-activation-in-the-arcuate-nucleus
#3
Steven A Lloyd, Beau Corkill, Matthew C Bruster, Rick L Roberts, Ryan A Shanks
Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis...
March 18, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28322979/3-4-methylenedioxymethamphetamine-mdma-ecstasy-produces-edema-due-to-bbb-disruption-induced-by-mmp-9-activation-in-rat-hippocampus
#4
Mercedes Pérez-Hernández, María Encarnación Fernández-Valle, Ana Rubio-Araiz, Rebeca Vidal, María Dolores Gutiérrez-López, Esther O'Shea, María Isabel Colado
The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats...
March 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28319548/tanshinone-iia-attenuates-sevoflurane-neurotoxicity-in-neonatal-mice
#5
Yimeng Xia, Heng Xu, Chenfei Jia, Xiaodong Hu, Yu Kang, Xiaoxuan Yang, Qingsheng Xue, Guorong Tao, Buwei Yu
BACKGROUND: Sevoflurane is the most widely used inhalational anesthetic in pediatric medicine. Despite this, sevoflurane has been reported to exert potentially neurotoxic effects on the developing brain. Clinical interventions and treatments for these effects are limited. Tanshinone IIA (Tan IIA), extracted from Salvia miltiorrhiza (Danshen), has been documented to alleviate cognitive decline in traditional applications. Therefore, we hypothesized that preadministration of Tan IIA may attenuate sevoflurane-induced neurotoxicity, suggesting that Tan IIA is a new and promising drug capable of counteracting the effects of cognitive dysfunction produced by general anesthetics...
April 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28317148/bortezomib-induced-peripheral-neuropathy-a-genome-wide-association-study-on-multiple-myeloma-patients
#6
Chiara Campo, Miguel Inacio da Silva Filho, Niels Weinhold, Seyed Hamidreza Mahmoudpour, Hartmut Goldschmidt, Kari Hemminki, Maximilian Merz, Asta Försti
The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment...
March 20, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28316031/transactivation-domain-of-human-c-myc-is-essential-to-alleviate-poly-q-mediated-neurotoxicity-in-drosophila-disease-models
#7
Kritika Raj, Surajit Sarkar
Polyglutamine (poly(Q)) disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, represent a group of neurological disorders which arise due to an atypically expanded poly(Q) tract in the coding region of the affected gene. Pathogenesis of these disorders inside the cells begins with the assembly of these mutant proteins in the form of insoluble inclusion bodies (IBs), which progressively sequester several vital cellular transcription factors and other essential proteins, and finally leads to neuronal dysfunction and apoptosis...
March 18, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28291734/safety-assessment-of-the-aqueous-extract-of-the-flowers-of-nymphaea-lotus-linn-nymphaeaceae-acute-neuro-and-subchronic-oral-toxicity-studies-in-albinos-wistar-rats
#8
Mireille Kameni Poumeni, Danielle Claude Bilanda, Paul Désiré Dzeufiet Djomeni, Yolande Sandrine Mengue Ngadena, Marguerite Francine Mballa, Madeleine Chantal Ngoungoure, Agnès Carolle Ouafo, Théophile Dimo, Pierre Kamtchouing
BACKGROUND: Nymphaea lotus Linn (N. lotus) is a medicinal plant widely used in Cameroon popular medicine, to treat neuropsychiatric conditions, male sexual disorders or as food supplement. However, scientific data on the pharmacotoxic profile of this plant are not available. The safety of N. lotus was assessed in acute, neuro- and subchronic toxicity studies by following the OECD guidelines. Effectively, no data have been published until now in regard to its safety on the nervous system...
March 14, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28286483/long-term-effects-pathophysiological-mechanisms-and-risk-factors-of-chemotherapy-induced-peripheral-neuropathies-a-comprehensive-literature-review
#9
REVIEW
Nicolas Kerckhove, Aurore Collin, Sakahlé Condé, Carine Chaleteix, Denis Pezet, David Balayssac
Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28286117/carvedilol-prevents-functional-deficits-in-peripheral-nerve-mitochondria-of-rats-with-oxaliplatin-evoked-painful-peripheral-neuropathy
#10
Aparna Areti, Prashanth Komirishetty, Ashutosh Kumar
Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a)...
March 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28284907/minocycline-protects-rescues-and-prevents-knockdown-transgenic-parkin-drosophila-against-paraquat-iron-toxicity-implications-for-autosomic-recessive-juvenile-parkinsonism
#11
Hector Flavio Ortega-Arellano, Marlene Jimenez-Del-Rio, Carlos Velez-Pardo
Autosomal recessive Juvenile Parkinsonism (AR-JP) is a chronic, progressive neurodegenerative disorder caused by mutation in the PARKIN gene, and invariably associated with dopaminergic (DAergic) neuronal loss and brain iron accumulation. Since current medical therapy is symptomatic and lacks significant disease-modifying effects, other treatment approaches are urgently needed it. In the present work, we investigate the role of minocycline (MC) in paraquat (PQ)/iron-induced neurotoxicity in the Drosophila TH>parkin-RNAi/+ (w[*]; UAS-parkin-RNAi; TH-GAL4) fly and have shown the following: (i) MC increased life span and restored the locomotor activity of knockdown (KD) transgenic parkin flies in comparison with the control (vehicle) group; (ii) MC at low (0...
March 8, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28274858/neurotoxicity-induced-by-methamphetamine-heroin-combination-in-pc12-cells
#12
Xiang Tian, Qin Ru, Qi Xiong, Kai Yue, Lin Chen, Baomiao Ma, Weimin Gan, Yuanren Si, Huqiao Xiao, Chaoying Li
Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. The combination of psychostimulants and opioids produces more serious effects than either drug alone and is responsible for numerous deaths. In recent years, owing to its increased use, methamphetamine (METH), a psychostimulant, has become a popular choice for use in combination with opioids, especially heroin. However, little is known about the neurotoxicity of METH/heroin combination. The aims of this study were to evaluate whether METH/heroin combination was more neurotoxic than either drug alone and analyze the possible neurotoxic mechanisms using rat pheochromocytoma (PC12) cells...
March 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28269783/modulating-the-balance-of-synaptic-and-extrasynaptic-nmda-receptors-shows-positive-effects-against-amyloid-%C3%AE-induced-neurotoxicity
#13
Yan Huang, Wei Shen, Jie Su, Bin Cheng, Dong Li, Gang Liu, Wen-Xia Zhou, Yong-Xiang Zhang
Alzheimer's disease (AD) patients suffer a disturbance in the balance between synaptic (GluN2A, mediating the protective pathway) and extrasynaptic NMDA receptors (NMDARs) (GluN2B, mediating the excitotoxic pathway), and, therefore, restoring the balance of GluN2A and GluN2B should be beneficial for AD. In this study, the GluN2B-selective antagonist, ifenprodil, and the non-selective NMDAR agonist, NMDA, had little effect on amyloid-β (Aβ)-induced long-term potentiation deficits. Enhancing the activity of GluN2A had a protective effect against Aβ, and specific activation of GluN2A and inhibition of GluN2B showed a better protective effect...
March 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28260103/protective-effect-of-arctigenin-on-ethanol-induced-neurotoxicity-in-pc12-cells
#14
Jia Huang, Lan Xiao, Jing-Xiang Wei, Ya-Hai Shu, Shi-Qi Fang, Yong-Tang Wang, Xiu-Min Lu
As a neurotropic substance, ethanol can damage nerve cells through an increase in the production of free radicals, interference of neurotrophic factor signaling pathways, activation of endogenous apoptotic signals and other molecular mechanisms. Previous studies have revealed that a number of natural drugs extracted from plants offer protection of nerve cells from damage. Among these, arctigenin (ATG) is a lignine extracted from Arctium lappa (L.), which has been found to exert a neuroprotective effect on scopolamine‑induced memory deficits in mice with Alzheimer's disease and glutamate-induced neurotoxicity in primary neurons...
February 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28256519/autophagy-down-regulates-pro-inflammatory-mediators-in-bv2-microglial-cells-and-rescues-both-lps-and-alpha-synuclein-induced-neuronal-cell-death
#15
Claudio Bussi, Javier Maria Peralta Ramos, Daniela S Arroyo, Emilia A Gaviglio, Jose Ignacio Gallea, Ji Ming Wang, Maria Soledad Celej, Pablo Iribarren
Autophagy is a fundamental cellular homeostatic mechanism, whereby cells autodigest parts of their cytoplasm for removal or turnover. Neurodegenerative disorders are associated with autophagy dysregulation, and drugs modulating autophagy have been successful in several animal models. Microglial cells are phagocytes in the central nervous system (CNS) that become activated in pathological conditions and determine the fate of other neural cells. Here, we studied the effects of autophagy on the production of pro-inflammatory molecules in microglial cells and their effects on neuronal cells...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28254502/maternal-exposure-to-titanium-dioxide-nanoparticles-during-pregnancy-and-lactation-alters-offspring-hippocampal-mrna-bax-and-bcl-2-levels-induces-apoptosis-and-decreases-neurogenesis
#16
Alireza Ebrahimzadeh Bideskan, Abbas Mohammadipour, Alireza Fazel, Hossein Haghir, Houshang Rafatpanah, Mahmoud Hosseini, Aliakbar Rajabzadeh
INTRODUCTION: The usage of Titanium dioxide nanoparticles (TiO2-NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO2-NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO2-NPs on rat offspring hippocampus during developmental period...
February 26, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28241493/neuronal-stress-and-injury-caused-by-hiv-1-cart-and-drug-abuse-converging-contributions-to-hand
#17
REVIEW
Ana B Sanchez, Marcus Kaul
Multiple mechanisms appear to contribute to neuronal stress and injury underlying HIV-associated neurocognitive disorders (HAND), which occur despite the successful introduction of combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can itself be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine (METH), seems to compromise antiretroviral therapy and aggravate HAND. However, the combined effect of virus and recreational and therapeutic drugs on the brain is still incompletely understood...
February 23, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28239323/metronidazole-induced-encephalopathy-in-a-patient-with-crohn-s-disease
#18
Jihye Kim, Jaeyoung Chun, Jae Yong Park, Seung Wook Hong, Joo Young Lee, Jin Woo Kang, Seongjun Hwang, Sang-Bae Ko, Jong Pil Im, Joo Sung Kim
Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug...
January 2017: Intestinal Research
https://www.readbyqxmd.com/read/28212938/the-combined-effects-of-3-4-methylenedioxymethamphetamine-mdma-and-selected-substituted-methcathinones-on-measures-of-neurotoxicity
#19
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 16, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28212849/hydrogen-sulfide-endoplasmic-reticulum-stress-and-alcohol-mediated-neurotoxicity
#20
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
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