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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/28820078/effects-of-excitotoxic-lesion-with-inhaled-anesthetics-on-nervous-system-cells-of-rodents
#1
Maria Fernanda Quiroz Padilla, Gemma Guillazo-Blanch, Magdy Sanchez, Maria Andrea Dominguez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28808138/an-ampk-dependent-regulatory-pathway-in-tau-mediated-toxicity
#2
Alessia Galasso, Charles S Cameron, Bruno G Frenguelli, Kevin G Moffat
Neurodegenerative tauopathies are characterized by accumulation of hyperphosphorylated tau aggregates primarily degraded by autophagy.The 5'AMP-activated protein kinase (AMPK) is expressed in most cells, including neurons. Alongside its metabolic functions, it is also known to be activated in Alzheimer's brains, phosphorylate tau and be a critical autophagy activator. Whether it plays a neurotoxic or neuroprotective role remains unclear. Complexly in tauopathies, while stress conditions can result in AMPK activation enhancing tau-mediated toxicity, AMPK activation is not always concomitant with autophagic induction...
August 14, 2017: Biology Open
https://www.readbyqxmd.com/read/28807678/metformin-lowers-%C3%AE-synuclein-phosphorylation-and-upregulates-neurotrophic-factor-in-the-mptp-mouse-model-of-parkinson-s-disease
#3
Nikita Katila, Sunil Bhurtel, Sina Shadfar, Sunil Srivastav, Sabita Neupane, Uttam Ojha, Gil-Saeng Jeong, Dong-Young Choi
In spite of the massive research for the identification of neurorestorative or neuroprotective intervention for curing Parkinson's disease (PD), there is still lack of clinically proven neuroprotective agents. Metformin, a common anti-hyperglycemic drug has been known to possess neuroprotective properties. However, specific mechanisms by which metformin protects neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity remain to be elucidated. In this study, we assessed the neuroprotective effects of metformin in the subchronic MPTP model of PD, and explored its feasible mechanisms for neuroprotection...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807675/substantial-protection-against-mptp-associated-parkinson-s-neurotoxicity-in-vitro-and-in-vivo-by-anti-cancer-agent-su4312-via-activation-of-mef2d-and-inhibition-of-mao-b
#4
Baojian Guo, Shengquan Hu, Chengyou Zheng, Hongyu Wang, Fangcheng Luo, Haitao Li, Wei Cui, Xifei Yang, Guozhen Cui, Shinghung Mak, Tony Chung-Lit Choi, Edmond Dik-Lung Ma, Yuqiang Wang, Simon Ming Yuen Lee, Zaijun Zhang, Yifan Han
We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinson's disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28806057/rational-design-and-multi-biological-profiling-of-novel-donepezil-trolox-hybrids-against-alzheimer-s-disease-with-cholinergic-antioxidant-neuroprotective-and-cognition-enhancing-properties
#5
Pei Cai, Si-Qiang Fang, Xue-Lian Yang, Jia-Jia Wu, Qiao-Hong Liu, Hao Hong, Xiao-Bing Wang, Lingyi Kong
A novel series of donepezil-trolox hybrids were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41...
August 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28782144/syndrome-of-inappropriate-antidiuretic-hormone-secretion-from-concomitant-use-of-itraconazole-and-vindesine
#6
H Zhou, L Li, Y Zhou, Y Han
WHAT IS KNOWN AND OBJECTIVE: Several studies have reported that itraconazole-induced inhibition of vincristine (VCR) metabolism might result in neurological impairment and syndrome of inappropriate antidiuretic hormone (SIADH). However, there are few reports concerning adverse drug reactions (ADRs) resulting from concomitant use of vindesine (VDS) and itraconazole. Here, we report the first case of adverse drug interactions (ADIs) between itraconazole and VDS in a Chinese child with acute lymphocytic leukaemia (ALL)...
August 6, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28770436/in-vitro-and-ex-vivo-neurotoxic-effects-of-efavirenz-are-greater-than-those-of-other-common-antiretrovirals
#7
Vincent T Ciavatta, Edyta K Bichler, Iris A Speigel, Courtney C Elder, Shavonne L Teng, William R Tyor, Paul S García
Although antiretroviral (ARV) therapy has reduced the incidence of severe dementia associated with HIV infection, there has been a rise in milder neurocognitive complaints. Data from HIV patients taking ARVs have shown measurable neurocognitive improvements during drug cessation, suggesting a neurotoxic role of the therapy itself. Mechanisms underlying potential ARV neurotoxicity have not been thoroughly investigated, however pathologic oxidative stress and mitochondrial dysfunction have been suspected. Using DIV 16 primary rat cortical neuron culture, we tested eight ARVs from the three most commonly prescribed ARV classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) for effects on neuron viability and morphology after 24 h of drug exposure...
August 2, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28760072/omega-3-fatty-acid-attenuates-oxidative-stress-in-cerebral-cortex-cerebellum-and-hippocampus-tissue-and-improves-neurobehavioral-activity-in-chronic-lead-induced-neurotoxicity
#8
Pramod Kumar Singh, Manish Kumar Singh, Rajesh Singh Yadav, Rajendra Nath, Anju Mehrotra, Akash Rawat, Rakesh Kumar Dixit
OBJECTIVES: In view of the increasing risk of lead on human health, the present study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid on chronic lead-induced neurotoxicity and behavioral impairment in rats. METHODS: Different neurobehavioral parameters, biochemical assays, and histopathological analyses in brain regions of rats were conducted. RESULTS: Rats exposed to different doses of lead (lead acetate 2...
August 1, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28750834/protective-effect-of-atorvastatin-on-d-galactose-induced-aging-model-in-mice
#9
Elham Kaviani, Mohammadreza Rahmani, Ayat Kaeidi, Ali Shamsizadeh, Mohamad Allahtavakoli, Nazanin Mozafari, Iman Fatemi
Atorvastatin (Ator), competitive inhibitors of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, is a cholesterol lowering drug. Ator has been shown to have neuroprotective, antioxidant and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. Here we assessed the effect of Ator on the d-galactose (d-gal)-induced aging in mice. For this purpose, Ator (0.1 and 1mg/kg/p.o.), was administrated daily in d-gal-received (500mg/kg/p.o.) mice model of aging for six weeks...
July 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28731367/methamphetamine-causes-photoreceptor-cell-damage-through-promoting-polarization-of-macrophages-and-inducing-inflammatory-response
#10
Aihui Zhang, Laiwei Wu, Zilin Chen, Guoqiang Huang, Xiaohe Lu
Classically activated macrophages (M1) are proinflammatory effectors and closely related to the progression of neurotoxicity. As a powerful psychostimulant and addictive drug, methamphetamine (Meth) abuse could result in long-lasting abnormalities in retina. This study investigated the effect of Meth at nontoxic concentration on macrophage activation state and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by Meth on 661 W cells after coculturing with RAW264.7 macrophage...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28729624/taxanes-and-platinum-derivatives-impair-schwann-cells-via-distinct-mechanisms
#11
Satoshi Imai, Madoka Koyanagi, Ziauddin Azimi, Yui Nakazato, Mayuna Matsumoto, Takashi Ogihara, Atsushi Yonezawa, Tomohiro Omura, Shunsaku Nakagawa, Shuji Wakatsuki, Toshiyuki Araki, Shuji Kaneko, Takayuki Nakagawa, Kazuo Matsubara
Impairment of peripheral neurons by anti-cancer agents, including taxanes and platinum derivatives, has been considered to be a major cause of chemotherapy-induced peripheral neuropathy (CIPN), however, the precise underlying mechanisms are not fully understood. Here, we examined the direct effects of anti-cancer agents on Schwann cells. Exposure of primary cultured rat Schwann cells to paclitaxel (0.01 μM), cisplatin (1 μM), or oxaliplatin (3 μM) for 48 h induced cytotoxicity and reduced myelin basic protein expression at concentrations lower than those required to induce neurotoxicity in cultured rat dorsal root ganglion (DRG) neurons...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724203/huprine-x-attenuates-the-neurotoxicity-induced-by-kainic-acid-especially-brain-inflammation
#12
J Relat, B Pérez, P Camps, D Muñoz-Torrero, A Badia, M V Clos
Huprine X (HX) is a synthetic anticholinesterasic compound that exerts a potent inhibitory action on acetylcholinesterase (AChE) activity, an agonist effect on cholinergic receptors, neuroprotective activity in different neurotoxicity models in vivo and in vitro and cognition enhancing effects in non-transgenic (C57BL/6) and transgenic (3xTg-AD, APPswe) mice. In the present study, we assessed the ability of HX (0.8 mg/kg, 21 days) to prevent the damage induced by kainic acid (KA; 28 mg/kg) regarding apoptosis, glia reactivity and neurogenesis in mouse brain...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28714389/a-peptide-based-pro-drug-ameliorates-amyloid-%C3%AE-induced-neuronal-apoptosis-in-in-vitro-sh-sy5y-cells
#13
Sourav Kumar, Ashim Paul, Sourav Kalita, Awanish Kumar, Saurabh Srivastav, Somoday Hazra, Anup Kumar Ghosh, Bhubaneswar Mandal, Amal Chandra Mondal
BACKGROUND: Alzheimer's disease (AD), a common protein misfolding neurodegenerative disorder, is one of the most common forms of dementia. Amyloid precursor protein (APP) derived amyloid-β (Aβ) proteins accumulated into interneuronal spaces and plays a crucial role in the disease progression and its pathology. The aggregated Aβ exerts its neurotoxic effects by inducing apoptosis and oxidative damage in neuronal cells. OBJECTIVES: We have investigated the effects of a synthesized Pro-Drug peptide (PDp) on Aβ1-40 induced cytotoxicity in human neuroblastoma SH-SY5Y cells, represents one of the most effective strategies in combating human AD...
July 13, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28703078/chrysophanol-suppresses-pro-inflammatory-response-in-microglia-via-regulation-of-drp1-dependent-mitochondrial-fission
#14
Unbin Chae, Ju-Sik Min, Hanna Lee, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
OBJECTIVES: Chrysophanol, also called chrysophanic acid, is a natural anthraquinone compound found in Rheum palmatum. R. palmatum has been used in oriental medicine in ancient East Asia. Microglial cells represent not only the forefront immune defense in the central nervous system but also the most reactive sensors to various threats. However, activated microglia can exert neurotoxic effects via excessive production of cytotoxic molecules and proinflammatory cytokines. Therefore, modulation of microglial cell activation is important for maintaining neuronal function...
July 13, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28699522/targeting-human-astrocytes-calcium-sensing-receptors-for-treatment-of-alzheimer-s-disease
#15
Anna Chiarini, Ubaldo Armato, James F Whitfield, Ilaria Dal Pra
Understanding the pathophysiology of Alzheimer's disease (AD) in the principal human neural cells is necessary for finding therapeutics for this illness. To help do this, we have been using freshly cultured functionally normal cerebral cortical adult human astrocytes (NAHAs) and postnatal neurons. The findings show that amyloid-β oligomers (Aβ-os) binding to calcium-sensing receptors (CaSRs) on NAHAs and neuron surfaces trigger signals capable of driving AD pathogenesis. This Aβ•CaSR signalling shifts the amyloid precursor protein (APP) from its α-secretase shedding producing neurotrophic/neuroprotective soluble (s)APPα to its β-secretase cleaving engendering AD-driving Aβ42/Aβ42-os peptides...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28694175/daily-consumption-of-methylene-blue-reduces-attentional-deficits-and-dopamine-reduction-in-a-6-ohda-model-of-parkinson-s-disease
#16
Elizabeth S Smith, Madeline E Clark, Gwendolyn A Hardy, David J Kraan, Elisa Biondo, F Gonzalez-Lima, Lawrence K Cormack, Marie Monfils, Hongjoo J Lee
Recently, alternative drug therapies for Parkinson's disease (PD) have been investigated as there are many shortcomings of traditional dopamine-based therapies including difficulties in treating cognitive and attentional dysfunction. A promising therapeutic avenue is to target mitochondrial dysfunction and oxidative stress in PD. One option might be the use of methylene blue (MB), an antioxidant and metabolic enhancer. MB has been shown to improve cognitive function in both intact rodents and rodent disease models...
July 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/28685675/the-beneficial-effects-of-sulfur-containing-amino-acids-on-cisplatin-induced-cardiotoxicity-and-neurotoxicity-in-rodents
#17
Gvozden Rosic, Jovana Joksimovic, Dragica Selakovic, Vladimir Jakovljevic, Vladimir Zivkovic, Ivan Srejovic, Marko Djuric, Dragan Djuric
Cisplatin is one the most frequently used chemotherapeutic drugs for several decades. Although its antineoplastic effect has been reported in treatment of numerous malignances, various adverse effects seem to be the crucial limiting factor for its administration. Beside the most commonly described nephro- and hepatotoxicity, cisplatin therapy is also accompanied with gastrointestinal, reproductive, hematological, cardiovascular and neurological side effects. Since it has been reported that cisplatin induce oxidative damage in various tissues (by means of altered ROS production, as well as by depletion of antioxidants), it seems reasonable that huge efforts had been put in the investigations of antioxidant supplementation as potential therapeutical approach for attenuation of cisplatin toxicities...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28684237/monoaminergic-toxicity-induced-by-cathinone-phthalimide-an-in-vitro-study
#18
Susan M Lantz, Hector Rosas-Hernandez, Elvis Cuevas, Bonnie Robinson, Kenner C Rice, William E Fantegrossi, Syed Z Imam, Merle G Paule, Syed F Ali
Bath salts, or synthetic cathinones, have cocaine-like or amphetamine-like properties and induce psychoactive effects via their capacity to modulate serotonin (5-HT) and dopamine (DA). Structurally distinct synthetic cathinones are continuously being generated to skirt existing drug laws. One example of these modified compounds is cathinone phthalimide (CP), which has already appeared on the global market. The lack of toxicological studies on the effects of CP on monoaminergic systems led to the development of the present study in order to generate an acute toxicity profile for CP, and to clarify whether it primarily affects both dopamine and serotonin, like the synthetic cathinones mephedrone and methylone, or primarily affects dopamine, like 3, 4-methylenedioxypyrovalerone (MDPV)...
August 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28668652/an-integrative-investigation-of-the-toxicity-of-aconiti-kusnezoffii-radix-and-the-attenuation-effect-of-its-processed-drug-using-a-uhplc-q-tof-based-rat-serum-and-urine-metabolomics-strategy
#19
Zhenyu Sui, Qing Li, Lin Zhu, Zhenru Wang, Chunxiao Lv, Ran Liu, Huarong Xu, Bosai He, Zuojing Li, Kaishun Bi
Aconiti kusnezoffii radix (AKR), the root of Aconitum kusnezoffii Reichb., is commonly used in the treatment of the rheumatoid arthritis. However, the clinical application is limited due to its potential toxicity. Therefore, to investigate the mechanism of its potential neurotoxicity and nephrotoxicity, a comprehensive metabolomics study combined with serum biochemistry and histopathology measurements was carried out. A UHPLC-Q-TOF mass spectrometry based metabolomics approach was applied to characterize the AKR toxicity, while the toxicity attenuation effects of Aconiti kusnezoffii radix cocta (AKRC) on Wistar rats were also investigated...
June 21, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28668282/brain-infusion-of-%C3%AE-synuclein-oligomers-induces-motor-and-non-motor-parkinson-s-disease-like-symptoms-in-mice
#20
Juliana T S Fortuna, Matthias Gralle, Danielle Beckman, Fernanda S Neves, Luan P Diniz, Paula S Frost, Fernanda Barros-Aragão, Luís E Santos, Rafaella A Gonçalves, Luciana Romão, Daniele C Zamberlan, Felix A A Soares, Carolina Braga, Debora Foguel, Flávia C A Gomes, Fernanda G De Felice, Sergio T Ferreira, Julia R Clarke, Cláudia P Figueiredo
Parkinson's disease (PD) is characterized by motor dysfunction, which is preceded by a number of non-motor symptoms including olfactory deficits. Aggregation of α-synuclein (α-syn) gives rise to Lewy bodies in dopaminergic neurons and is thought to play a central role in PD pathology. However, whether amyloid fibrils or soluble oligomers of α-syn are the main neurotoxic species in PD remains controversial. Here, we performed a single intracerebroventricular (i.c.v.) infusion of α-syn oligomers (α-SYOs) in mice and evaluated motor and non-motor symptoms...
August 30, 2017: Behavioural Brain Research
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