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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/29228978/asiatic-acid-attenuates-methamphetamine-induced-neuroinflammation-and-neurotoxicity-through-blocking-of-nf-kb-stat3-erk-and-mitochondria-mediated-apoptosis-pathway
#1
Ji-Hyun Park, Young Ho Seo, Jung-Hee Jang, Chul-Ho Jeong, Sooyeun Lee, Byoungduck Park
BACKGROUND: Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway...
December 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29219629/pharmacotherapy-options-for-managing-chemotherapy-induced-peripheral-neurotoxicity
#2
Guido Cavaletti, Paola Marmiroli
Prevention and treatment of chemotherapy-induced peripheral neurotoxicity (CIPN) are clinically-relevant unmet needs. Despite extensive efforts at the preclinical and clinical levels, no effective pharmacological interventions are available, and this unsatisfactory situation reflects a combination of methodological issues and a lack of effectiveness of the tested drugs. Areas covered: This non-systematic, but unbiased review is based on published papers available in PubMed and screened using the broad search string [chemotherapy (and) neuropathy (and) treatment] to analyze the reported data...
December 8, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29214892/rutin-hydrate-ameliorates-cadmium-chloride-induced-spatial-memory-loss-and-neural-apoptosis-in-rats-by-enhancing-levels-of-acetylcholine-inhibiting-jnk-and-erk1-2-activation-and-activating-mtor-signalling
#3
Ghada A Abdel-Aleem, Eman F Khaleel
This study aimed at studying the potential neuroprotective effect of Rutin hydrate (RH) alone or in conjugation with α-tocopherol against cadmium chloride (CdCl2)-induced neurotoxicity and cognitive impairment in rats and to investigate the mechanisms of action. Rats intoxicated with CdCl2 were treated with the vehicle, RH, α-tocopherol or combined treatment were examined, and compared to control rats received vehicle or individual doses of either drug. Data confirmed that RH improves spatial memory function by increasing acetylcholine availability, boosting endogenous antioxidant potential, activating cell survival and inhibiting apoptotic pathways, an effect that is more effective when RH was conjugated with α-tocopherol...
December 7, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29210076/in-vitro-effect-of-antiretroviral-drugs-on-cultured-primary-astrocytes-analysis-of-neurotoxicity-and-matrix-metalloproteinase-inhibition
#4
Tiziana Latronico, Ilaria Pati, Rossana Ciavarella, Anna Fasano, Fabio Mengoni, Miriam Lichtner, Vincenzo Vullo, Claudio Maria Mastroianni, Grazia Maria Liuzzi
There is little information available on the possible toxic effects that antiretroviral (ARV) drugs used for the treatment of human immunodeficiency virus (HIV)-infected subjects, may have on the central nervous system (CNS) resident cells. Moreover, it is unclear whether the efficacy of the ARV drugs may also be due to their ability to exert extravirological effects on factors responsible for the development of HIV brain injury, e.g. matrix metalloproteinases (MMPs). This study investigates the toxicity of three different ARV drugs and on their ability to modulate levels and expression of gelatinases A (MMP-2) and B (MMP-9) in astrocytes...
December 6, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29197621/inhibition-of-histone-deacetylase-6-hdac6-protects-against-vincristine-induced-peripheral-neuropathies-and-inhibits-tumor-growth
#5
Lawrence Van Helleputte, Mandy Kater, Dana P Cook, Caroline Eykens, Elisabeth Rossaert, Wanda Haeck, Tom Jaspers, Natasja Geens, Pieter Vanden Berghe, Conny Gysemans, Chantal Mathieu, Wim Robberecht, Philip Van Damme, Guido Cavaletti, Matthew Jarpe, Ludo Van Den Bosch
As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy...
November 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29197543/role-of-dopamine-d1-receptor-in-3-fluoromethamphetamine-induced-neurotoxicity-in-mice
#6
Phuong-Tram Nguyen, Eun-Joo Shin, Duy-Khanh Dang, Hai-Quyen Tran, Choon-Gon Jang, Ji Hoon Jeong, Yu Jeung Lee, Hyo Jong Lee, Yong Sup Lee, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
3-Fluoromethamphetamine (3-FMA) is an illegal designer drug of methamphetamine (MA) derivative. Up to date, little is known about the neurotoxic potential of 3-FMA. In the present study, we investigated the role of dopamine receptors in neurotoxicity induced by 3-FMA in comparison with MA (35 mg/kg, i.p.) as a control drug. Here we found that 3-FMA (40, 60 or 80 mg/kg, i.p.) produced mortality in a dose-dependent manner in mice. Treatment with 3-FMA (40 mg/kg, i.p.) resulted in significant hyperthermia, oxidative stress and microgliosis (microglial differentiation into M1 phenotype) followed by pro-apoptotic changes and the induction of terminal deoxynucleotidyl transferase dUDP nick end labeling (TUNEL)-positive cells...
November 29, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29191802/peripheral-neuropathy-induced-by-microtubule-targeted-chemotherapies-insights-into-acute-injury-and-long-term-recovery
#7
Krystyna M Wozniak, James J Vornov, Ying Wu, Ying Liu, Valentina A Carozzi, Virginia Rodriquez-Menendez, Elisa Ballarini, Paola Alberti, Eleonora Pozzi, Sara Semperboni, Brett M Cook, Bruce A Littlefield, Kenichi Nomoto, Krista Condon, Sean Eckley, Christopher DesJardins, Leslie Wilson, Mary Ann Jordan, Stuart C Feinstein, Guido Cavaletti, Michael Polydefkis, Barbara S Slusher
Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations in preclinical model systems have focused on either behaviors or acute changes in nerve conduction velocity (NCV) and amplitude, but greater understanding of the underlying nature of axonal injury and its long-term processes is needed as cancer patients live longer. In this study, we used multiple independent endpoints to systematically characterize CIPN recovery in mice exposed to the anti-tubulin cancer drugs eribulin (ERIB), ixabepilone (IXA), paclitaxel (PACLI) or vinorelbine (VINO) at maximal tolerated doses...
November 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/29180229/peroxisomes-contribute-to-oxidative-stress-in-neurons-during-doxorubicin-based-chemotherapy
#8
Jose F Moruno-Manchon, Ndidi-Ese Uzor, Shelli R Kesler, Jeffrey S Wefel, Debra M Townley, Archana Sidalaghatta Nagaraja, Sunila Pradeep, Lingegowda S Mangala, Anil K Sood, Andrey S Tsvetkov
Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy...
November 24, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29176325/cav2-3-r-type-calcium-channels-are-critical-for-mediating-anticonvulsive-and-neuroprotective-properties-of-lamotrigine-in-vivo
#9
Maxine Dibué-Adjei, Marcel A Kamp, Serdar Alpdogan, Etienne E Tevoufouet, Wolfram F Neiss, Jürgen Hescheler, Toni Schneider
BACKGROUND/AIMS: Lamotrigine (LTG) is a popular modern antiepileptic drug (AED), however, its mechanism of action has yet to be fully understood, as it is known to modulate many members of several ion channel families. In heterologous systems, LTG inhibits Cav2.3 (R-type) calcium currents, which contribute to kainic-acid- (KA) induced epilepsy in vivo. To gain insight into the role of R-type currents in LTG drug action in vivo, we compared the effects of LTG to topiramate and lacosamide in Cav2...
November 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29156432/the-effects-of-human-drugs-in-corbicula-fluminea-assessment-of-neurotoxicity-inflammation-gametogenic-activity-and-energy-status
#10
G V Aguirre-Martínez, C André, F Gagné, L M Martín-Díaz
The constant release of pharmaceuticals products to aquatic environment even at low concentrations (ng L(-1) to µg L(-1)) could lead to unknown chronic effects to non-target organisms. The aim of this study was to evaluate neurotoxic responses, inflammation, gametogenic activity and energy status on the fresh water clam C. fluminea after exposure to different concentrations of caffeine (CAF), ibuprofen (IBU), carbamazepine (CBZ), novobiocin (NOV) and tamoxifen (TMX) for 21 days under laboratory conditions...
November 17, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#11
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29150331/anti-amyloidogenic-and-anti-apoptotic-effect-of-%C3%AE-bisabolol-against-a%C3%AE-induced-neurotoxicity-in-pc12-cells
#12
Balakrishnan Shanmuganathan, Venkatesan Suryanarayanan, Sethuraman Sathya, Muralidharan Narenkumar, Sanjeev Kumar Singh, Kandasamy Ruckmani, Kasi Pandima Devi
Alzheimer's disease (AD) is a life-threatening neurodegenerative disorder leading to dementia, with a progressive decline in memory and other thinking skills of elderly populace. Of the multiple etiological factors of AD, the accumulation of senile plaques (SPs) particularly as Aβ oligomers correlates with the relentlessness cognitive impairment in AD patients and play a vital role in AD pathology. Since natural essential oil constituents have successfully served as a source of drugs for AD treatment, the present study aims at the in vitro and in silico investigation of anti-amyloidogenic potential and anti-apoptotic property of the α-bisabolol against Aβ25-35 induced neurotoxicity in PC12 cells...
October 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29146197/illicit-drug-ketamine-induces-adverse-effects-from-behavioral-alterations-and-oxidative-stress-to-p53-regulated-apoptosis-in-medaka-fish-under-environmentally-relevant-exposures
#13
Pei-Han Liao, Wen-Kai Yang, Ching-Hsin Yang, Chun-Hon Lin, Chin-Chu Hwang, Pei-Jen Chen
With increasing problems of drug abuse worldwide, aquatic ecosystems are contaminated by human pharmaceuticals from the discharge of hospital or municipal effluent. However, ecotoxicity data and related toxic mechanism for neuroactive controlled or illicit drugs are still lacking, so assessing the associated hazardous risk is difficult. This study aims to investigate the behavioral changes, oxidative stress, gene expression and neurotoxic or apoptosis effect(s) in larvae of medaka fish (Oryzias latipes) with environmentally relevant exposures of ketamine (KET) solutions for 1-14 days...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29142460/efficacy-and-safety-of-duloxetine-in-chinese-breast-cancer-patients-with-paclitaxel-induced-peripheral-neuropathy
#14
Jiani Wang, Qing Li, Binghe Xu, Tongtong Zhang, Shanshan Chen, Yang Luo
Objective: Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients' quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy (PIPN) in Chinese breast cancer patients. Methods: A total of 102 patients with a median age of 50 (range, 25-60) years, treated in the Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, between November 2014 and January 2017 were finally enrolled...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29137682/cefepime-induced-neurotoxicity-a-systematic-review
#15
Lauren E Payne, David J Gagnon, Richard R Riker, David B Seder, Elizabeth K Glisic, Jane G Morris, Gilles L Fraser
BACKGROUND: Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations...
November 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29134560/neurochemical-and-neurotoxic-effects-of-mdma-ecstasy-and-caffeine-after-chronic-combined-administration-in-mice
#16
Anna Maria Górska, Katarzyna Kamińska, Agnieszka Wawrzczak-Bargieła, Giulia Costa, Micaela Morelli, Ryszard Przewłocki, Grzegorz Kreiner, Krystyna Gołembiowska
MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration...
November 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29129847/effects-of-ketoconazole-on-cyclophosphamide-metabolism-evaluation-of-cyp3a4-inhibition-effect-using-the-in-vitro-and-in-vivo-models
#17
Le Yang, Chenyang Yan, Feng Zhang, Bo Jiang, Shouhong Gao, Youtian Liang, Lifeng Huang, Wansheng Chen
Cyclophosphamide (CP) is widely used in anticancer therapy regimens and 2-dechloroethylcyclophosphamide (DECP) is its side-chain dechloroethylated metabolite. N-dechloroethylation of CP mediated by the enzyme CYP3A4 yields nephrotoxic and neurotoxic chloroacetaldehyde (CAA) in equimolar amount to DECP. This study aimed to evaluate the inhibitory effect of ketoconazole (KTZ) on CP metabolism through in vitro and in vivo drug-drug interaction (DDI) research. Long-term treatment of KTZ induces hepatic injury; thus single doses of KTZ at low, middle, and high levels (10, 20, and 40 mg/kg) were investigated for pharmacokinetic DDI with CP...
November 13, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29125463/pharmacological-augmentation-of-nicotinamide-phosphoribosyltransferase-nampt-protects-against-paclitaxel-induced-peripheral-neuropathy
#18
Peter M LoCoco, April L Risinger, Hudson R Smith, Teresa S Chavera, Kelly A Berg, William P Clarke
Chemotherapy-induced peripheral neuropathy (CIPN) arises from collateral damage to peripheral afferent sensory neurons by anticancer pharmacotherapy, leading to debilitating neuropathic pain. No effective treatment for CIPN exists, short of dose-reduction which worsens cancer prognosis. Here we report that stimulation of nicotinamide phosphoribosyltransferase (NAMPT) produced robust neuroprotection in an aggressive CIPN model utilizing the frontline anticancer drug, paclitaxel (PTX). Daily treatment of rats with the first-in-class NAMPT stimulator, P7C3-A20, prevented behavioral and histologic indicators of peripheral neuropathy, stimulated tissue NAD recovery, improved general health, and abolished attrition produced by a near maximum-tolerated dose of PTX...
November 10, 2017: ELife
https://www.readbyqxmd.com/read/29105512/changes-in-the-metabolome-and-microrna-levels-in-biological-fluids-might-represent-biomarkers-of-neurotoxicity-a-trimethyltin-study
#19
Syed Z Imam, Zhen He, Elvis Cuevas, Hector Rosas-Hernandez, Susan M Lantz, Sumit Sarkar, James Raymick, Bonnie Robinson, Joseph P Hanig, David Herr, Denise MacMillan, Aaron Smith, Serguei Liachenko, Sherry Ferguson, James O'Callaghan, Diane Miller, Christopher Somps, Ingrid D Pardo, William Slikker, Jennifer B Pierson, Ruth Roberts, Binsheng Gong, Weida Tong, Michael Aschner, Mary J Kallman, David Calligaro, Merle G Paule
Neurotoxicity has been linked with exposure to a number of common drugs and chemicals, yet efficient, accurate, and minimally invasive methods to detect it are lacking. Fluid-based biomarkers such as those found in serum, plasma, urine, and cerebrospinal fluid have great potential due to the relative ease of sampling but at present, data on their expression and translation are lacking or inconsistent. In this pilot study using a trimethyl tin rat model of central nervous system toxicity, we have applied state-of-the-art assessment techniques to identify potential individual biomarkers and patterns of biomarkers in serum, plasma, urine or cerebral spinal fluid that may be indicative of nerve cell damage and degeneration...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29095437/metformin-ameliorates-arsenic-trioxide-hepatotoxicity-via-inhibiting-mitochondrial-complex-i
#20
Sunbin Ling, Qiaonan Shan, Peng Liu, Tingting Feng, Xuanyu Zhang, Penghui Xiang, Kangchen Chen, Haiyang Xie, Penghong Song, Lin Zhou, Jimin Liu, Shusen Zheng, Xiao Xu
Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects...
November 2, 2017: Cell Death & Disease
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