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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/28645087/ep2-receptor-agonist-ono-ae1-259-01-attenuates-pentylenetetrazole-and-pilocarpine-induced-seizures-but-causes-hippocampal-neurotoxicity
#1
Aline Carré Santos, Fernanda Rossatto Temp, Joseane Righes Marafiga, Micheli Mainardi Pillat, Amanda Titzel Hessel, Leandro Rodrigo Ribeiro, Lígia Gomes Miyazato, Mauro Schneider Oliveira, Carlos Fernando Mello
Epilepsy is a common and devastating neurological disease affecting more than 50 million people worldwide. Accumulating experimental and clinical evidence suggests that inflammatory pathways contribute to the development of seizures in various forms of epilepsy. In this context, while the activation of the PGE2 EP2 receptor causes early neuroprotective and late neurotoxic effects, the role of EP2 receptor in seizures remains unclear. We investigated whether the systemic administration of the highly selective EP2 agonist ONO-AE1-259-01 prevented acute pentylenetetrazole (PTZ)- and pilocarpine-induced seizures...
June 20, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#2
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28643232/caffeine-protects-against-anticonvulsant-induced-neurotoxicity-in-the-developing-rat-brain
#3
Stefanie Endesfelder, Ulrike Weichelt, Cornelia Schiller, Marco Sifringer, Ivo Bendix, Christoph Bührer
Phenobarbital is the most commonly used drug for the treatment of neonatal seizures but may induce neurodegeneration in the developing brain. Methylxanthine caffeine is used for the treatment of apnea in newborn infants and appears to be neuroprotective, as shown by antiapoptotic and anti-inflammatory effects in oxidative stress models in newborn rodents and reduced rates of cerebral palsy in human infants treated with caffeine. We hypothesized that caffeine may counteract the proapoptotic effects of phenobarbital in newborn rats...
June 22, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28642731/efficacy-of-drug-interventions-for-chemotherapy-induced-chronic-peripheral-neurotoxicity-a-network-meta-analysis
#4
Xiying Fu, Huijie Wu, Jinyao Li, Can Wang, Ming Li, Qianqian Ma, Wei Yang
Peripheral neurotoxicity is a disturbing issue for cancer patients who are treated with chemotherapy. Several medications have been developed for preventing chemotherapy-induced chronic neurotoxicity (CICNT) however; their relative efficacies have not yet been studied. In this study, we conducted a network meta-analysis to give intervention recommendations. The literature was searched in a variety of databases and eligible studies were chosen based on predefined criteria. Data extraction and statistical analysis was performed, and the results are displayed using the odds ratio (OR) and corresponding 95% credible intervals (CrI) with respect to overall and severe neurotoxicity...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28636017/effect-of-cisplatin-on-the-transport-activity-of-pii-type-atpases
#5
Francesco Tadini-Buoninsegni, Giacomo Sordi, Serena Smeazzetto, Giovanni Natile, Fabio Arnesano
Cisplatin (cis-diamminedichlorido-Pt(ii)) is extensively used as a chemotherapeutic agent against various types of tumors. However, cisplatin administration causes serious side effects, including nephrotoxicity, ototoxicity and neurotoxicity. It has been shown that cisplatin can interact with P-type ATPases, e.g., Cu(+)-ATPases (ATP7A and ATP7B) and Na(+),K(+)-ATPase. Cisplatin-induced inhibition of Na(+),K(+)-ATPase has been related to the nephrotoxic effect of the drug. To investigate the inhibitory effects of cisplatin on the pumping activity of PII-type ATPases, electrical measurements were performed on sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+),K(+)-ATPase embedded in vesicles/membrane fragments adsorbed on a solid-supported membrane...
June 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28621212/methamphetamine-causes-neurotoxicity-by-promoting-polarization-of-macrophages-and-inflammatory-response
#6
X Li, F Wu, L Xue, B Wang, J Li, Y Chen, T Chen
Macrophages, especially their activation state, are closely related to the progression of neurotoxicity. Classically activated macrophages (M1) are proinflammatory effectors, while alternatively activated macrophages (M2) exhibit anti-inflammatory properties. As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (Meth) abuse may lead to long-lasting abnormalities in the neuronal system. The present study investigated the effect of Meth at subtoxic concentration on macrophage activation state and its underlying toxicity to neuronal cells...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28620884/kinetic-pharmacodynamic-model-of-chemotherapy-induced-peripheral-neuropathy-in-patients-with-metastatic-breast-cancer-treated-with-paclitaxel-nab-paclitaxel-or-ixabepilone-calgb-40502-alliance
#7
Shailly Mehrotra, Manish R Sharma, Elizabeth Gray, Kehua Wu, William T Barry, Clifford Hudis, Eric P Winer, Alan P Lyss, Deborah L Toppmeyer, Alvaro Moreno-Aspitia, Thomas E Lad, Mario Valasco, Beth Overmoyer, Hope Rugo, Mark J Ratain, Jogarao V Gobburu
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity caused by several chemotherapeutic agents. Currently, CIPN is managed by empirical dose modifications at the discretion of the treating physician. The goal of this research is to quantitate the dose-CIPN relationship to inform the optimal strategies for dose modification. Data were obtained from the Cancer and Leukemia Group B (CALGB) 40502 trial, a randomized phase III trial of paclitaxel vs. nab-paclitaxel vs. ixabepilone as first-line chemotherapy for locally recurrent or metastatic breast cancer...
June 15, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28600844/pain-in-chemotherapy-induced-peripheral-neurotoxicity
#8
REVIEW
Paola Marmiroli, Arianna Scuteri, David R Cornblath, Guido Cavaletti
Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a potentially dose-limiting side effect of the treatment of several cancers. CIPN is predominantly or exclusively sensory, and it is frequently associated with unpleasant symptoms, overall referred to as "pain". However, given the markedly different clinical presentation and course of CIPN depending on the antineoplastic drug used, the broad term "pain" in the specific context of CIPN needs to be reconsidered and refined. In fact, a precise identification of the features of CIPN has relevant implication in the design of rational-based clinical trials and in the selection of possible active drugs...
June 10, 2017: Journal of the Peripheral Nervous System: JPNS
https://www.readbyqxmd.com/read/28597409/progression-and-persistence-of-neurotoxicity-induced-by-mdma-in-dopaminergic-regions-of-the-mouse-brain-and-association-with-noradrenergic-gabaergic-and-serotonergic-damage
#9
Giulia Costa, Micaela Morelli, Nicola Simola
The amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) is known to induce neurotoxic damage in dopaminergic regions of the mouse brain. In order to characterize how the number of administrations influenced the severity of MDMA-induced dopaminergic damage and to describe the localization and persistence of this damage, we evaluated the changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) in different regions of the mouse brain. Moreover, we investigated whether dopaminergic damage was associated with noradrenergic, GABAergic, and serotonergic damage, by evaluating the changes in noradrenaline transporter (NET), glutamic acid decarboxylase-67 (GAD-67), and serotonin transporter (SERT)...
June 9, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28595944/ido-chronic-immune-activation-and-tryptophan-metabolic-pathway-a-potential-pathophysiological-link-between-depression-and-obesity
#10
REVIEW
Adriano José Maia Chaves Filho, Camila Nayane Carvalho Lima, Silvânia Maria Mendes Vasconcelos, David Freitas de Lucena, Michael Maes, Danielle Macedo
Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs)...
June 5, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28593578/induced-pluripotent-stem-cell-based-modeling-of-neurodegenerative-diseases-a-focus-on-autophagy
#11
REVIEW
Johannes Jungverdorben, Andreas Till, Oliver Brüstle
The advent of cell reprogramming has enabled the generation of induced pluripotent stem cells (iPSCs) from patient skin fibroblasts or blood cells and their subsequent differentiation into tissue-specific cells, including neurons and glia. This approach can be used to recapitulate disease-specific phenotypes in classical cell culture paradigms and thus represents an invaluable asset for disease modeling and drug validation in the framework of personalized medicine. The autophagy pathway is a ubiquitous eukaryotic degradation and recycling system, which relies on lysosomal degradation of unwanted and potentially cytotoxic components...
June 7, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28562386/neurotoxicity-of-anesthetic-drugs-an-update
#12
Federico Bilotta, Lis A Evered, Shaun E Gruenbaum
PURPOSE OF REVIEW: This article reviews the most recently published evidence that investigated anesthesia-induced neurotoxicity in both animals and humans, especially as it pertains to the perinatal period. RECENT FINDINGS: Several recent studies have focused on better understanding the complex mechanisms that underlie intravenous and volatile anesthesia-induced neurotoxicity in animals. Adjuvant agents that target these pathways have been investigated for their effectiveness in attenuating the neuroapoptosis and neurocognitive deficits that result from anesthesia exposure, including dexmedetomidine, rutin, vitamin C, tumor necrosis factor α, lithium, apocynin, carreic acid phenethyl ester...
May 27, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28532421/glutamate-excitotoxicity-induced-by-orally-administered-propionic-acid-a-short-chain-fatty-acid-can-be-ameliorated-by-bee-pollen
#13
Afaf El-Ansary, Huda S Al-Salem, Alqahtani Asma, Abeer Al-Dbass
BACKGROUND: Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups. METHODS: Twenty-four young male Western Albino rats 3-4 weeks of age, and 45-60 g body weight were enrolled in the present study...
May 22, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28527032/methylone-and-mdpv-activate-autophagy-in-human-dopaminergic-sh-sy5y-cells-a-new-insight-into-the-context-of-%C3%AE-keto-amphetamines-related-neurotoxicity
#14
Maria João Valente, Cristina Amaral, Georgina Correia-da-Silva, José Alberto Duarte, Maria de Lourdes Bastos, Félix Carvalho, Paula Guedes de Pinho, Márcia Carvalho
Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity has hitherto not been investigated. In the present study, we show that two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), elicit morphological changes consistent with autophagy and neurodegeneration, including formation of autophagic vacuoles and neurite retraction in dopaminergic SH-SY5Y cells...
May 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28507726/adapting-tissue-engineered-in-vitro-cns-models-for-high-throughput-study-of-neurodegeneration
#15
Caitriona O'Rourke, Charlotte Lee-Reeves, Rosemary Al Drake, Grant Ww Cameron, A Jane Loughlin, James B Phillips
Neurodegenerative conditions remain difficult to treat, with the continuing failure to see therapeutic research successfully advance to clinical trials. One of the obstacles that must be overcome is to develop enhanced models of disease. Tissue engineering techniques enable us to create organised artificial central nervous system tissue that has the potential to improve the drug development process. This study presents a replicable model of neurodegenerative pathology through the use of engineered neural tissue co-cultures that can incorporate cells from various sources and allow degeneration and protection of neurons to be observed easily and measured, following exposure to neurotoxic compounds - okadaic acid and 1-methyl-4-phenylpyridinium...
January 2017: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/28505155/oxidative-stress-and-expression-of-insulin-signaling-proteins-in-the-brain-of-diabetic-rats-role-of-nigella-sativa-oil-and-antidiabetic-drugs
#16
Mahmoud Balbaa, Shaymaa A Abdulmalek, Sofia Khalil
BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28504195/fgf18-protects-against-6-hydroxydopamine-induced-nigrostriatal-damage-in-a-rat-model-of-parkinson-s-disease
#17
Xingzhi Guo, Tingting Liu, Diandian Zhao, Xiaofeng Wang, Dongmei Liu, Yang He, Chang Shan, Yingying Kong, Weiwei Hu, Bei Tao, Lihao Sun, Hongyan Zhao, Shengtian Li, Jianmin Liu
Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD). However, the underlying mechanism of this injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in midbrain development and has been reported to protect neurons from ischemic injury, we investigated whether FGF18 exerted a protective effect on dopaminergic neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3β signaling pathway...
May 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28495355/tafenoquine-is-not-neurotoxic-following-supertherapeutic-dosing-in-rats
#18
Geoffrey S Dow, Tracey Brown, Mark Reid, Bryan Smith, Stephen Toovey
BACKGROUND: Tafenoquine is a new drug for malaria prevention. The goal of the present work was to conduct a specific neurobehavioral study in rats with histopathological assessment of the brain. METHODS: The clinical, hematological, behavioral, motor activity, and neurohistopathologic changes induced by different dose levels of tafenoquine were evaluated following single super-therapeutic dose administration. Toxicokinetic data were generated to allow extrapolation to clinical exposures...
May 8, 2017: Travel Medicine and Infectious Disease
https://www.readbyqxmd.com/read/28487766/malathion-increases-apoptotic-cell-death-by-inducing-lysosomal-membrane-permeabilization-in-n2a-neuroblastoma-cells-a-model-for-neurodegeneration-in-alzheimer-s-disease
#19
Ramu Venkatesan, Yong Un Park, Eunhee Ji, Eui-Ju Yeo, Sun Yeou Kim
Malathion is an organophosphate with severe neurotoxic effects. Upon acute exposure, malathion initially enhances cholinergic activity by inhibition of acetylcholinesterase, which is its major pathological mechanism. Malathion also induces non-cholinergic neuronal cell death in neurodegenerative conditions; the associated molecular mechanism is not well-characterized. To investigate the molecular mechanism of malathion-induced cell death, N2a mouse neuroblastoma cells were exposed to malathion and cell death-related parameters were examined...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28470518/ferroptosis-and-cell-death-analysis-by-flow-cytometry
#20
Daishi Chen, Ilker Y Eyupoglu, Nicolai Savaskan
Cell death and its recently discovered regulated form ferroptosis are characterized by distinct morphological, electrophysiological, and pharmacological features. In particular ferroptosis can be induced by experimental compounds and clinical drugs (i.e., erastin, sulfasalazine, sorafenib, and artesunate) in various cell types and cancer cells. Pharmacologically, this cell death process can be inhibited by iron chelators and lipid peroxidation inhibitors. Relevance of this specific cell death form has been found in different pathological conditions such as cancer, neurotoxicity, neurodegeneration, and ischemia...
2017: Methods in Molecular Biology
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