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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/28731367/methamphetamine-causes-photoreceptor-cell-damage-through-promoting-polarization-of-macrophages-and-inducing-inflammatory-response
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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)...
July 3, 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
#10
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
#11
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...
June 29, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28657934/multitarget-botanical-pharmacotherapy-in-major-depression-a-toxic-brain-hypothesis
#12
Siu W Tang, Wayne H Tang, Brain E Leonard
A significant number of patients with major depression do not respond optimally to current antidepressant drugs. As depression is likely to be a heterogeneous disorder, it is possible that existing neurotransmitter-based antidepressant drugs do not fully address other pathologies that may exist in certain cases. Biological pathologies related to depression that have been proposed and studied extensively include inflammation and immunology, hypercortisolemia, oxidative stress, and impaired angiogenesis. Such pathologies may induce neurodegeneration, which in turn causes cognitive impairment, a symptom increasingly being recognized in depression...
June 27, 2017: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28656087/toxicology-effects-of-berberis-vulgaris-barberry-and-its-active-constituent-berberine-a-review
#13
REVIEW
Seyede Zohre Kamrani Rad, Maryam Rameshrad, Hossein Hosseinzadeh
Berberis vulgaris and berberine, its main component, traditionally have been used for treatment of various disorders. The pharmacological properties of them have been investigated using different in vivo and in vitro models. In spite of beneficial effects of B. vulgaris on different cell lines, there are documents have revealed negative impacts of it on animal and human. In this regards, the determination of its toxicity in a scientific view is necessary. In current report, we provide classified information about the toxicity of B...
May 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28655613/int131-increases-dendritic-arborization-and-protects-against-a%C3%AE-toxicity-by-inducing-mitochondrial-changes-in-hippocampal-neurons
#14
Juan A Godoy, Juan M Zolezzi, Nibaldo C Inestrosa
In previous studies, we have demonstrated the beneficial effects of classic PPARγ agonists on neuroprotection against Aβ oligomer neurotoxicity in a double transgenic mouse model of Alzheimer' disease (AD). INT-131, a novel, non-thiazolidinedione compound that belongs to a new family of drugs, selective PPARγ modulators (SPPARMs), has provided an emerging opportunity for the treatment of type 2 diabetes mellitus and metabolic syndrome. However, its role in the central nervous system has not been studied...
June 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28653974/hla-g-3-utr-polymorphisms-predict-drug-induced-g3-4-toxicity-related-to-folinic-acid-5-fluorouracil-oxaliplatin-folfox4-chemotherapy-in-non-metastatic-colorectal-cancer
#15
Marica Garziera, Saverio Virdone, Elena De Mattia, Lucia Scarabel, Erika Cecchin, Jerry Polesel, Mario D'Andrea, Nicoletta Pella, Angela Buonadonna, Adolfo Favaretto, Giuseppe Toffoli
Polymorphisms in drug-metabolizing enzymes might not completely explain inter-individual differences in toxicity profiles of patients with colorectal cancer (CRC) that receive folinic acid/5-fluorouracil/oxaliplatin (FOLFOX4). Recent data indicate that the immune system could contribute to FOLFOX4 outcomes. In light of the immune inhibitory nature of human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, we aimed to identify novel genomic markers of grades 3 and 4 (G3-4) toxicity related to FOLFOX4 therapy in patients with CRC...
June 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28650104/alzheimer-s-disease-and-metabolic-syndrome-a-link-from-oxidative-stress-and-inflammation-to-neurodegeneration
#16
REVIEW
Eduardo Rojas-Gutierrez, Guadalupe Muñoz-Arenas, Samuel Treviño, Blanca Espinosa, Raúl Chavez, Karla Rojas, Gonzalo Flores, Alfonso Díaz, Jorge Guevara
Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles (NFT). Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome (MetS) and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage...
June 26, 2017: Synapse
https://www.readbyqxmd.com/read/28645087/ep2-receptor-agonist-ono-ae1-259-01-attenuates-pentylenetetrazole-and-pilocarpine-induced-seizures-but-causes-hippocampal-neurotoxicity
#17
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
#18
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
#19
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
#20
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
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