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Drug induced neurotoxicity

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28461881/impact-of-tramadol-and-morphine-abuse-on-the-activities-of-acetylcholine-esterase-na-k-atpase-and-related-parameters-in-cerebral-cortices-of-male-adult-rats
#9
Abd El-Hamid Mohamed Elwy, Ghada Tabl
OBJECTIVE: To determine the effect of the most commonly abused drugs (tramadol and morphine), on acetylcholine esterase (AChE), Na(+)/K(+)-ATPase activities and related parameters, Na(+) and K(+) as biomarkers of neurotoxicity. METHODS: Tramadol - as a weak μ opioid receptor agonist- and morphine - as opiate analgesic drugs, were chosen for the present study. Four series of experimental animals were conducted for either tramadol or morphine: control series; repeated single equal doses (therapeutic dose) series; cumulative increasing doses series and delay (withdrawal) series (96 hours withdrawal period after last administration), at time period intervals 7, 14 and 21 days...
March 2017: Electronic Physician
https://www.readbyqxmd.com/read/28435263/neuroprotection-against-apoptosis-of-sk-n-mc-cells-using-rmp-7-and-lactoferrin-grafted-liposomes-carrying-quercetin
#10
Yung-Chih Kuo, Chien-Wei Tsao
A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood-brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28431970/effects-of-natural-and-synthetic-isothiocyanate-based-h2s-releasers-against-chemotherapy-induced-neuropathic-pain-role-of-kv7-potassium-channels
#11
Lorenzo Di Cesare Mannelli, Elena Lucarini, Laura Micheli, Ilaria Mosca, Paolo Ambrosino, Maria Virginia Soldovieri, Alma Martelli, Lara Testai, Maurizio Taglialatela, Vincenzo Calderone, Carla Ghelardini
Hydrogen sulfide (H2S) is a crucial signaling molecule involved in several physiological and pathological processes. Nonetheless, the role of this gasotransmitter in the pathogenesis and treatment of neuropathic pain is controversial. The aim of the present study was to investigate the pain relieving profile of a series of slow releasing H2S donors (the natural allyl-isothiocyanate and the synthetics phenyl- and carboxyphenyl-isothiocyanate) in animal models of neuropathic pain induced by paclitaxel or oxaliplatin, anticancer drugs characterized by a dose-limiting neurotoxicity...
April 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28424016/acute-brain-injury-following-illicit-drug-abuse-in-adolescent-and-young-adult-patients-spectrum-of-neuroimaging-findings
#12
Shai Shrot, Andrea Poretti, Elizabeth W Tucker, Bruno P Soares, Thierry Agm Huisman
The use of illicit drugs is currently a major medical problem among adolescents. Several illicit drugs have a high abuse potential and can be neurotoxic causing high morbidity and mortality. The clinical manifestation of adolescents with acute drug-induced neurotoxicity is often characterized by non-specific symptoms and findings. Early diagnosis is important to prevent death and permanent long-term neurological impairments. We report on clinical and neuroimaging findings in five adolescents with acute brain imaging following illicit drug intoxication to highlight the role of neuroimaging findings in the diagnostic work-up of pediatric acute drug-induced neurotoxicity...
April 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28421199/valproic-acid-protects-primary-dopamine-neurons-from-mpp-induced-neurotoxicity-involvement-of-gsk3%C3%AE-phosphorylation-by-akt-and-erk-through-the-mitochondrial-intrinsic-apoptotic-pathway
#13
Chi Zhang, Xianrui Yuan, Zhongliang Hu, Songlin Liu, Haoyu Li, Ming Wu, Jian Yuan, Zijin Zhao, Jun Su, Xiangyu Wang, Yiwei Liao, Qing Liu
Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP(+) model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28410131/substance-use-disorder-a-bio-directional-subset-of-reward-deficiency-syndrome
#14
Kenneth Blum, Mark Gold, Zsolt Demetrovics, Trevor Archer, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan
This commentary is to inform clinicians challenged with an increase in people seeking treatment for Substance Use Disorder (SUD), that the ninety percent revolving door, is, in part, due to post-withdrawal, untreated neurotoxicity. This impairment attenuates neurotransmitter signaling and compromises resting state functional connectivity, leading to unwanted sequelae including depression, sleep disturbances, sensation seeking, lack of satisfaction and impulsivity. Neuroimaging studies indicate that neurobiological recovery can take years...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28397504/-chemotherapy-related-cognitive-impairment-in-patients-with-hodgkin-lymphoma-pathophysiology-and-risk-factors
#15
D Fayette, Ľ Gahérová, H Móciková, J Marková, T Kozák, J Horáček
BACKGROUND: Cognitive impairment (impairment of memory, attention, or concentration) is documented in 17-75% of patients with various malignancies treated with chemotherapeutic agents that worsen quality of life. CRCI affects patients of all ages. The impairment of cognitive function in connection with chemotherapy is usually mild, but an event. relationship with dementia remains to be confirmed. Chemotherapy in combination with radiotherapy in Hodgkin lymphoma can cure 80-90% of patients...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28395522/nanotechnology-application-to-local-anaesthesia-la
#16
Mahmoud Reza Moradkhani, Arash Karimi, Babak Negahdari
Several advancements have been made on the exact release of local anaesthetics formulation and its efficiency at inducing motor and sensory block for an extended time has been harnessed in clinical practice. The use of sustained release formulations delivers analgesia for a lengthier period of time with one administration, thereby reducing complications that usually arise with administration of conventional analgesia. In addition, controlled release of an anaesthetic drug is said to prevent overdosing, reduced side effects, especially cardiotoxicity, neurotoxicity and tissue lesions...
April 10, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28391554/translesion-synthesis-dna-polymerase-kappa-is-indispensable-for-dna-repair-synthesis-in-cisplatin-exposed-dorsal-root-ganglion-neurons
#17
Ming Zhuo, Murat F Gorgun, Ella W Englander
In the peripheral nervous system (PNS) in the absence of tight blood barrier, neurons are at increased risk of DNA damage, yet the question of how effectively PNS neurons manage DNA damage remains largely unanswered. Genotoxins in systemic circulation include chemotherapeutic drugs that reach peripheral neurons and damage their DNA. Because neurotoxicity of platinum-based class of chemotherapeutic drugs has been implicated in PNS neuropathies, we utilized an in vitro model of Dorsal Root Ganglia (DRGs) to investigate how peripheral neurons respond to cisplatin that forms intra- and interstrand crosslinks with their DNA...
April 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28386520/behavioral-and-stereological-analysis-of-the-effects-of-intermittent-feeding-diet-on-the-orally-administrated-mdma-ecstasy-in-mice
#18
Zeinab Ebrahimian, Zeinab Karimi, Mohammad Javad Khoshnoud, Mohammad Reza Namavar, Bahram Daraei, Mohsen Raza Haidari
Background: 3,4-methylenedioxy-methamphetamine or MDMA (also known as "ecstasy" or "molly") is a commonly abused drug that affects behavior and can lead to neuronal damage. Intermittent feeding is an effective dietary protocol that promotes neuroprotection and improves behavioral outcomes in animal models of neurotoxicity and neurodegenerative diseases. In this study, we investigated the behavioral and histological outcomes of the effect of intermittent feeding on the orally administered MDMA in mice. Methods: The animals (male albino mice) were divided into four groups: ad libitum (AL), intermittent feeding (IF) (food given every other day), and AL and IF control groups...
January 2017: Innovations in Clinical Neuroscience
https://www.readbyqxmd.com/read/28384882/polymyxin-b-induced-diffuse-cutaneous-hyperpigmentation
#19
Sandeep Lahiry, Shouvik Choudhury, Ayan Mukherjee, Prajesh Kiran Bhunya, Moumita Bala
Polymyxin B is a polypeptide-antibiotic, primarily used for resistant Gram-negative infections, first obtained from bacterium Bacillus polymyxa in the late 1940s. Antibiotic spectrum are restricted to mainly gram negative bacterias like Enterobacter, E. coli, Klebsiella, Salmonella, Pasteurella, Bordetella, Shigella; and particularly organisms like Pseudomonas aeruginosa and Acinetobacter baumannii, which are extremely potent to acquire antibiotic resistance. Side effects include neurotoxicity and acute renal tubular necrosis...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28374576/docking-based-design-and-synthesis-of-galantamine-ndash-camphane-hybrids-as-inhibitors-of-acetylcholinesterase
#20
Georgi Stavrakov, Irena Philipova, Dimitrina Zheleva-Dimitrova, Iva Valkova, Evdokiya Salamanova, Spiro Konstantinov, Irini Doytchinova
Galantamine (GAL) as an acetylcholinesterase inhibitor (AChEI) is among the main drugs approved for the treatment of Alzheimer's disease. It fits perfectly into acetylcholinesterase (AChE) binding gorge but it is too short to fill it. The amyloid beta (Aβ) peptide binds in the peripheral anionic site (PAS) at the entrance of the binding gorge of AChE and initiates the formation of amyloid plaques. The blockade of PAS prevents from AChE-induced Aβ aggregation. In the present study, we describe the design of a series of galantamine-camphane hybrids as AChEIs...
April 4, 2017: Chemical Biology & Drug Design
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