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Drug induced neurotoxicity

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https://www.readbyqxmd.com/read/29665383/impact-of-aging-alzheimer-s-disease-and-parkinson-s-disease-on-the-blood-brain-barrier-transport-of-therapeutics
#1
Yijun Pan, Joseph A Nicolazzo
Older people are at greater risk of medicine-induced toxicities resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein...
April 14, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29656349/the-designer-drug-3-fluoromethcathinone-induces-oxidative-stress-and-activates-autophagy-in-ht22-neuronal-cells
#2
Kamila Siedlecka-Kroplewska, Agata Wrońska, Grzegorz Stasiłojć, Zbigniew Kmieć
Synthetic cathinones are psychoactive substances, derivatives of a natural psychostimulant cathinone. Although many synthetic cathinones have lost their legal status in many countries, their abuse still continues worldwide. Recently, they have been reported to exert neurotoxic effects in vitro and in vivo. The molecular mechanisms of their action have not been fully elucidated. Recently, they have been linked to the induction of oxidative stress, autophagy, and apoptosis. The aim of this study was to investigate whether 3-fluoromethcathinone (3-FMC), a synthetic cathinone, is able to induce oxidative stress, autophagy, and apoptosis in HT22 immortalized mouse hippocampal cells...
April 14, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29644532/methamphetamine-induces-apoptosis-of-microglia-via-the-intrinsic-mitochondrial-dependent-pathway
#3
Anna V Sharikova, Elizabeth Quaye, Jun Yong Park, Maxwell C Maloney, Habben Desta, Ramkumar Thiyagarajan, Kenneth L Seldeen, Neil U Parikh, Parteet Sandhu, Alexander Khmaladze, Bruce R Troen, Stanley A Schwartz, Supriya D Mahajan
Methamphetamine (METH) is a drug of abuse, the acute and chronic use of which induces neurotoxic responses in the human brain, ultimately leading to neurocognitive disorders. Our goals were to understand the impact of METH on microglial mitochondrial respiration and to determine whether METH induces the activation of the mitochondrial-dependent intrinsic apoptosis pathway in microglia. We assessed the expression of pro- apoptosis genes using qPCR of RNA extracted from a human microglial cell line (HTHU). We examined the apoptosis-inducing effects of METH on microglial cells using digital holographic microscopy (DHM) to quantify real-time apoptotic volume decrease (AVD) in microglia in a noninvasive manner...
April 11, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29629511/repeated-administration-of-3-4-methylenedioxymethamphetamine-mdma-elevates-the-levels-of-neuronal-nitric-oxide-synthase-in-the-nigrostriatal-system-possible-relevance-to-neurotoxicity
#4
Giulia Costa, Micaela Morelli, Nicola Simola
Previous studies have consistently demonstrated that the amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) induces dopaminergic damage in the mouse brain, and that this effect is most marked in the nigrostriatal system. Moreover, it has been suggested that the overproduction of nitric oxide (NO) may participate in the dopaminergic damage induced by MDMA. To further elucidate this issue, we evaluated the levels of the enzyme nitric oxide synthase (nNOS), which catalyzes the production of NO, in mice treated with regimens of MDMA that induce progressive and persistent neurotoxicity in the dopaminergic nigrostriatal system...
April 9, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29627381/restorative-effect-of-l-dopa-treatment-against-ochratoxin-a-induced-neurotoxicity
#5
Pratiksha V Bhat, T Anand, Manu T Mohan, Farhath Khanum
The toxic effects of Ochratoxin A (OTA), a fungal secondary metabolite of the genera Aspergillus and Penicillium with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) a Parkinson inducing drug were investigated to evaluate the neurotoxic effects exerted by OTA. OTA is known to contaminate food and feedstuff leading to a wide range of toxicity like nephrotoxicity, hepatotoxicity, and immunotoxicity. However, due to the dearth of available information on the possible mechanisms of OTA neurotoxicity and neurodegeneration the current study was undertaken...
April 5, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29626288/evidence-for-intrathecal-sodium-butyrate-as-a-novel-option-for-leptomeningeal-metastasis
#6
Hidemitsu Nakagawa, Yoshihiro Yui, Satoru Sasagawa, Kazuyuki Itoh
INTRODUCTION: The prognosis for leptomeningeal metastasis (LM) remains extremely poor regardless of intrathecal chemotherapy with various drugs, and thus, new treatments are necessary. Butyrate is an endogenous 4-carbon saturated fatty acid, has been investigated as an anti-tumor agent because of its multiple suppressive effects on several tumors. In this study, we investigated the cellular basis of sodium butyrate (SB), a sodium salt compound of butyrate, in vitro and evaluated the clinical potential of intrathecal SB administration for LM in vivo...
April 6, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29615861/lead-induced-atypical-parkinsonism-in-rats-behavioral-electrophysiological-and-neurochemical-evidence-for-a-role-of-noradrenaline-depletion
#7
Mariam Sabbar, Claire Delaville, Philippe De Deurwaerdère, Nouria Lakhdar-Ghazal, Abdelhamid Benazzouz
Background: Lead neurotoxicity is a major health problem known as a risk factor for neurodegenerative diseases, including the manifestation of parkinsonism-like disorder. While lead is known to preferentially accumulate in basal ganglia, the mechanisms underlying behavioral disorders remain unknown. Here, we investigated the neurophysiological and biochemical correlates of motor deficits induced by sub-chronic injections of lead. Methods: Sprague Dawely rats were exposed to sub-chronic injections of lead (10 mg/kg, i...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29614669/harpagoside-rescues-the-memory-impairments-in-chronic-cerebral-hypoperfusion-rats-by-inhibiting-pten-activity
#8
Chen Chen, Haifeng Zhang, Hongliang Xu, Rui Xue, Yake Zheng, Tianwen Wu, Yajun Lian
Vascular dementia (VaD) is the second most common dementia worldwide. Unlike Alzheimer's disease, VaD does not yet have effective therapeutic drugs. Harpagoside is the most important component extracted from Harpagophytum procumbens, a traditional Chinese medicine that has been widely used. The neuroprotective effects of harpagoside have been studied in Aβ- and MPTP-induced neurotoxicity. However, whether harpagoside is protective against VaD is not clear. In this study, with the use of chronic cerebral hypoperfusion rats, a well-known VaD model, we demonstrated that chronic administration (two months) of harpagoside was able to restore both the spatial learning/memory and fear memory impairments...
March 24, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29592839/high-resolution-mass-spectrometry-based-methodologies-for-identification-of-etravirine-bioactivation-to-reactive-metabolites-in-vitro-and-in-vivo-approaches
#9
Ana L A Godinho, Inês L Martins, João Nunes, Catarina Charneira, Jorge Grilo, Diogo M Silva, Sofia A Pereira, Karina Soto, M Conceição Oliveira, M Matilde Marques, Cristina C Jacob, Alexandra M M Antunes
Drug bioactivation to reactive metabolites capable of covalent adduct formation with bionucleophiles is a major cause of drug-induced adverse reactions. Therefore, elucidation of reactive metabolites is essential to unravel the toxicity mechanisms induced by drugs and thereby identify patient subgroups at higher risk. Etravirine (ETR) was the first second-generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) to be approved, as a therapeutic option for HIV-infected patients who developed resistance to the first-generation NNRTIs...
March 25, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29582256/probiotic-treatment-reduces-the-autistic-like-excitation-inhibition-imbalance-in-juvenile-hamsters-induced-by-orally-administered-propionic-acid-and-clindamycin
#10
Afaf El-Ansary, Abir Ben Bacha, Geir Bjørklund, Nora Al-Orf, Ramesa Shafi Bhat, Nadine Moubayed, Kawther Abed
Increasing evidence suggests that the gut microbiota plays a key role in the central nervous system (CNS), and alterations of the gut microbiota composition due to environmental factors can contribute to neurodevelopmental disorders. Animal modeling may help to identify drugs that can normalize the altered gut microbiota and thereby ameliorate abnormal brain signaling pathways. The purpose of the present study was to investigate the therapeutic potency of probiotics such as Bifidobacteria and Lactobacilli on glutamate excitotoxicity as a neurotoxic effect induced by clindamycin and propionic acid (PPA) in juvenile hamsters...
March 27, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29571023/pretreatment-with-taurine-prevented-brain-injury-and-exploratory-behaviour-associated-with-administration-of-anticancer-drug-cisplatin-in-rats
#11
Olatunde Owoeye, Isaac A Adedara, Ebenezer O Farombi
The neurotoxicity associated with cisplatin treatment is one of the major side effects compromising the efficacy of the anti-cancer treatment. The present study investigated the possible protective effects of taurine, an intracellular amino acid, on cisplatin-induced brain injury and exploratory behaviour using five groups of ten female rats each. Group I received drinking water only. Group II orally received taurine alone at 200 mg/kg whereas Group III received cisplatin alone intraperitoneally at 10 mg/kg...
March 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29566486/discovery-of-benzenesulfonamide-derivatives-as-carbonic-anhydrase-inhibitors-with-effective-anti-convulsant-action-design-synthesis-and-pharmacological-evaluation
#12
Chandra Bhushan Mishra, Shikha Kumari, Andrea Angeli, Silvia Bua, Manisha Tiwari, Claudiu T Supuran
Two series of novel benzenesulfonamide derivatives were synthesized and evaluated for their human carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against four isoforms, hCA I, hCA II, hCA VII and hCA IX. It was found that compounds of both series showed low to medium nanomolar inhibitory potential against all isoforms. Some of these derivatives displayed selective inhibition against the epileptogenesis-associated isoforms hCA II and VII, within the nanomolar range. These potent hCA II and VII inhibitors were evaluated as anticonvulsant agents against MES as well as sc-PTZ induced convulsions...
March 22, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29560440/chronic-voluntary-oral-methamphetamine-induces-deficits-in-spatial-learning-and-hippocampal-protein-kinase-mzeta-with-enhanced-astrogliosis-and-cyclooxygenase-2-levels
#13
Jorge A Avila, Roseanna M Zanca, Denis Shor, Nicholas Paleologos, Amber A Alliger, Maria E Figueiredo-Pereira, Peter A Serrano
Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA...
February 2018: Heliyon
https://www.readbyqxmd.com/read/29560079/fluorogold-labeled-organotypic-retinal-explant-culture-for-neurotoxicity-screening-studies
#14
Adrian Smedowski, Marita Pietrucha-Dutczak, Ruchi Maniar, Michael Ajeleti, Iwona Matuszek, Joanna Lewin-Kowalik
Preclinical toxicity screening of the new retinal compounds is an absolute requirement in the pathway of further drug development. Since retinal neuron cultivation and in vivo studies are relatively expensive and time consuming, we aimed to create a fast and reproducible ex vivo system for retinal toxicity screening. For this purpose, we used rat retinal explant culture that was retrogradely labeled with the FluoroGold before the isolation. Explants were exposed to a toxic concentration of gentamicin and ciliary neurotrophic factor (CNTF), a known neuroprotective agent...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29557360/neuroprotective-effects-of-statins-against-amyloid-%C3%AE-induced-neurotoxicity
#15
REVIEW
Hsin-Hua Li, Chih-Li Lin, Chien-Ning Huang
A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD). In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ) levels by affecting amyloid precursor protein (APP) cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD...
February 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29551974/neurobehavioral-effects-of-cephalosporins-assessment-of-locomotors-activity-motor-and-sensory-development-in-zebrafish
#16
Ying Han, Yangmin Zheng, Jingpu Zhang, Changqin Hu
Most third- and fourth-generation cephalosporins, such as cefotaxime, cefmenoxime, cefepime, and cefpirome, contain an aminothiazoyl ring at the C-7 position. Drug impurity, which may be produced either during synthesis or upon degradation, can induce adverse effects. Various reports have indicated that neurotoxicity is a side effect of cephalosporin. In this study, we developed methods for assessing the free-swimming activities and behaviors in zebrafish larvae in response to continuous darkness and stimulation of light-to-dark photoperiod transition by chemical treatments...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29547827/pharmacological-characterization-of-the-cannabinoid-receptor-2-agonist-%C3%AE-caryophyllene-on-seizure-models-in-mice
#17
Jana Tchekalarova, Keylla da Conceição Machado, Antonio Luiz Gomes Júnior, Ana Amélia de Carvalho Melo Cavalcante, Albena Momchilova, Rumyana Tzoneva
PURPOSE: Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice. METHODS: Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test...
March 12, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29530454/neuropharmacological-evaluation-on-four-traditional-herbs-used-as-nervine-tonic-and-commonly-available-as-shankhpushpi-in-india
#18
Neeraj K Sethiya, Alok Nahata, Pawan Kumar Singh, S H Mishra
OBJECTIVE: The present study was undertaken to evaluate the neuropharmacological effect of four herbs commonly identified as source of Shankhpushpi. BACKGROUND: Shankhpushpi is an Ayurvedic drug, widely used for its actions on the central nervous system, especially to improve intellect and boost memory. Four botanicals viz. Canscora decussata Schult. (CD), Clitorea ternatea Linn. (CT), Convolvulus pluricaulis Choisy. (CP) and Evolvulus alsinoides Linn. (EA) are considered as sources of Shankhpushpi by Indian practitioners on the basis of their morphological descriptions given in ancient texts...
March 9, 2018: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/29521239/hypnotic-effect-of-portulaca-oleracea-l-on-pentobarbital-induced-sleep-in-mice
#19
Shokouhsadat Hamedi, Fatemeh Forouzanfar, Hasan Rakhshandeh, Amirali Arian
OBJECTIVE: In Iranian Traditional Medicine, the herbs with cold and wet temperament can help to improve insomnia. Portulaca oleracea has cold and wet temperament, so the present study was carried out to investigate the sleep-prolonging effect of Portulaca oleracea. METHODS: This work was an experimental study on mice which were randomly divided into these groups: saline (control); Diazepam:) positive control); hydro-alcoholic extract of Portulaca oleracea (12.5, 25, 50, 75 and 100 mg/kg) by Soxhlet apparatus and maceration; in the effective (dose25 mg/kg), different fractions of extract were tested...
March 8, 2018: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29502215/identification-of-a-less-toxic-vinca-alkaloid-derivative-for-use-as-a-chemotherapeutic-agent-based-on-in-silico-structural-insights-and-metabolic-interactions-with-cyp3a4-and-cyp3a5
#20
Nikhat Saba, Alpana Seal
Vinca alkaloids are chemotherapeutic agents used in the treatment of both pediatric and adult cancer patients. Cytochrome P450 3A5 (CYP3A5) is 9- to 14-fold more efficient at clearing vincristine than cytochrome P450 3A4 (CYP3A4) is. However, patients who express an inactive form of the polymorphic CYP3A5 enzyme suffer from severe neurotoxicity during vincristine treatment, resulting in chemotherapy failure. Previous studies have found that the addition of new features to the parent drug can enhance its binding affinity to tubulin manyfold and could therefore yield novel anticancer drugs...
March 4, 2018: Journal of Molecular Modeling
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