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Natural compound peripheral neurotoxicity

Ankit Seth, Piyoosh A Sharma, Avanish Tripathi, Priyanka K Choubey, Pavan Srivastava, Prabhash N Tripathi, Sushant Kumar Shrivastava
BACKGROUND: Nipecotic acid is considered to be one of the most potent inhibitors of neuronal and glial γ- aminobutyric acid (GABA) uptake in vitro. However nipecotic acid does not readily cross the blood-brain barrier (BBB) following peripheral administration, owing to its hydrophilic nature. OBJECTIVE: A series of substituted acetonaphthones tethered nipecotic acid derivatives were designed and synthesized with an aim to improve the lipophilicity and the blood-brain barrier (BBB) permeation...
January 15, 2018: Medicinal Chemistry
Lorenzo Di Cesare Mannelli, Alessandra Pacini, Laura Micheli, Angelo Pietro Femia, Mario Maresca, Matteo Zanardelli, Alfredo Vannacci, Eugenia Gallo, Anna Rita Bilia, Giovanna Caderni, Fabio Firenzuoli, Alessandro Mugelli, Carla Ghelardini
Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. In the absence of effective pharmacological compounds, the opportunity to identify safe adjuvant treatments among medicinal plants seems appropriate. Astragali radix is an adaptogenic herbal product recently analyzed in platinum-treated cancer patients. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy...
February 10, 2017: Scientific Reports
Thiago Carrazoni, Marines de Avila Heberle, Ana Paula Artusi Perin, Ana Paula Zanatta, Polyana Veloso Rodrigues, Fabiola Duarte Machado Dos Santos, Carlos Gabriel Moreira de Almeida, Ricardo Vaz Breda, Douglas Silva Dos Santos, Paulo Marcos Pinto, Jaderson Costa da Costa, Celia Regina Carlini, Cháriston André Dal Belo
BACKGROUND: Ureases of Canavalia ensiformis are natural insecticides with a still elusive entomotoxic mode of action. We have investigated the mechanisms involved in the neurotoxicity induced by Jack Bean Urease (JBU) in Nauphoeta cinerea (Olivier). METHODS: To carry out this study we have employed biochemical and neurophysiological analysis of different cockroach organ systems. RESULTS AND CONCLUSIONS: The injection of the insects with JBU (0...
August 10, 2016: Toxicology
Kyoji Taguchi
Peripheral neuropathy is a common adverse effect of paclitaxel and oxaliplatin treatment. The major dose-limiting side effect of these drugs is peripheral sensory neuropathy. The symptoms of paclitaxel-induced neuropathy are mostly sensory and peripheral in nature, consisting of mechanical allodynia/hyperalgesia, tingling, and numbness. Oxaliplatin-induced neurotoxicity manifests as rapid-onset neuropathic symptoms that are exacerbated by cold exposure and as chronic neuropathy that develops after several treatment cycles...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Soghra Mehri, Mohammad Ali Meshki, Hossein Hosseinzadeh
Acrylamide (ACR) is a water-soluble monomer which has broad application in different industries and also can form in food during heating process. This monomer is a potent neurotoxic and damages the central and the peripheral nervous system in human and animals. Oxidative stress has been mentioned as an important pathway in ACR neurotoxicity, therefore the purpose of the current study was evaluation of possible effects of linalool which is a naturally enantiomer monoterpene compound. Linalool has shown antioxidant properties in several studies...
April 2015: Drug and Chemical Toxicology
K Ilavarasi, P Chermakani, S Arif Nisha, D Sheeja Malar, K Pandima Devi
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental toxin formed as an unintentional by-product of incomplete combustion. Several therapeutic approaches have evolved to combat its toxicity since it elicits immunotoxicity, neurotoxicity, hepatotoxicity, carcinogenicity and lethality. Search for drugs from natural resources especially from seaweeds has become intense due to their enormous pharmacological potential. Hence, the present study aims at revealing the protective effect of methanolic extract of G...
April 2015: Drug and Chemical Toxicology
Soghra Mehri, Hamed Veis Karami, Faezeh Vahdati Hassani, Hossein Hosseinzadeh
BACKGROUND: Acrylamide (ACR) is a well-known industrial toxic chemical that produces neurotoxicity, which is characterized by progressive central and peripheral neuronal degeneration. Chrysin is a natural, biologically active flavonoid compound, which is commonly found in many plants. The antioxidant and neuroprotective properties of chrysin have been demonstrated. METHODS: In this study, the possible effect of chrysin on ACR-induced toxicity was evaluated in both in vitro and in vivo experiments...
2014: Iranian Biomedical Journal
Dawn L Hershman, Joseph M Unger, Katherine D Crew, Lori M Minasian, Danielle Awad, Carol M Moinpour, Lisa Hansen, Danika L Lew, Heather Greenlee, Louis Fehrenbacher, James L Wade, Siu-Fun Wong, Gabriel N Hortobagyi, Frank L Meyskens, Kathy S Albain
PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN. PATIENTS AND METHODS: A 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) -Taxane scale at 12 weeks...
July 10, 2013: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Roberto Scelsi, Stefano M Candura
Many peripheral neuropathies are caused by the (acute or chronic) toxic action of metals, solvents, pesticides, and other occupational and environmental contaminants. These agents often reproduce the anatomoclinical pictures of hereditary (e.g., Charcot-Marie-Tooth disease), autoimmune (Guillain-Barrè syndrome), or dysmetabolic (thiamine deficiency, diabetic neuropathy) forms. Toxic peripheral neuropathies can be classified on the basis of etiology, clinical features (sensitive, motor, sensitive-motor), or histopathology: neuronopathies (uncommon, mostly secondary to retrograde axonal degeneration; e...
October 2012: Giornale Italiano di Medicina del Lavoro Ed Ergonomia
Jorge Estévez, Iris Mangas, Miguel Ángel Sogorb, Eugenio Vilanova
Organophosphorus compounds (OPs) cause neurotoxic disorders through interactions with well-known target esterases, such as acetylcholinesterase and neuropathy target esterase (NTE). However, the OPs can potentially interact with other esterases of unknown significance. Therefore, identifying, characterizing and elucidating the nature and functional significance of the OP-sensitive pool of esterases in the central and peripheral nervous systems need to be investigated. Kinetic models have been developed and applied by considering multi-enzymatic systems, inhibition, spontaneous reactivation, the chemical hydrolysis of the inhibitor and "ongoing inhibition" (inhibition during the substrate reaction time)...
March 25, 2013: Chemico-biological Interactions
Mansour S Al Moundhri, Suhail Al-Salam, Ahmed Al Mahrouqee, S Beegam, Badreldin H Ali
Cisplatin is commonly used against several solid tumors, and oxaliplatin is an effective cytotoxic drug used in colorectal cancer. A major clinical issue affecting 10-40 % of patients treated with cisplatin or oxaliplatin is severe peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with symptoms including cold sensitivity and neuropathic pain. The biochemical basis of the neurotoxicity is uncertain, but is associated with oxidative stress. Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer, and anti-inflammatory actions...
March 2013: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
Patrick G Morris, Monica N Fornier
Taxanes, derived from the bark of the Pacific yew tree, were the last major group of cytotoxic agents to be developed. Their proven efficacy in a variety of malignancies has constituted a real breakthrough in the treatment of cancer. Wider clinical use of taxanes has several important limitations, including acquired and intrinsic tumor resistance, hypersensitivity reactions, and cumulative neurotoxicity and hematopoietic toxicity. Epothilones, naturally occurring macrolide antibiotics that also act on the microtubule, are a novel class of compounds that may circumvent some of these problems...
February 2009: Clinical Advances in Hematology & Oncology: H&O
Paola Milla, Mario Airoldi, Günther Weber, Anne Drescher, Ulrich Jaehde, Luigi Cattel
Oxaliplatin is a promising drug for cancer therapy and the oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) regimen has become the standard adjuvant treatment for colorectal cancer. However, the oxaliplatin-induced neurotoxicity still represents a clinical problem leading to a discontinuation of the therapy. Many strategies have been proposed in order to manage the neurotoxicity, but their effect on antitumoral efficacy is still unclear. In this study, we investigated the effect of reduced glutathione administration on neurotoxicity, oxaliplatin pharmacokinetics, and platinum-DNA (Pt-DNA) adduct formation in patients affected by colorectal cancer treated with FOLFOX4 adjuvant regimen...
June 2009: Anti-cancer Drugs
Albert L Shroads, Xu Guo, Vaishali Dixit, Hui-Ping Liu, Margaret O James, Peter W Stacpoole
Dichloroacetate (DCA) is an investigational drug for certain metabolic diseases. It is biotransformed principally by the zeta-1 family isoform of glutathione transferase (GSTz1), also known as maleylacetoacetate isomerase (MAAI), which catalyzes the penultimate step in tyrosine catabolism. DCA causes a reversible peripheral neuropathy in several species, including humans. However, recent clinical trials indicate that adults are considerably more susceptible to this adverse effect than children. We evaluated the kinetics and biotransformation of DCA and its effects on tyrosine metabolism in nine patients treated for 6 months with 25 mg/kg/day and in rats treated for 5 days with 50 mg/kg/day...
March 2008: Journal of Pharmacology and Experimental Therapeutics
Lucia Helena Martini, Lucas Cereser, Isaac Zanonato Junior, Fluvia Melina Alves Jardim, Deusa Aparecida Vendite, Marcos Emilio dos Santos Frizzo, Rosendo A Yunes, João Batista Calixto, Susana Wofchuk, Diogo O Souza
Natural products including those derived from plants, have over the years greatly contributed to the development of therapeutic drugs. Polygodial and drimanial are sesquiterpenes isolated from the bark of the plant Drymis Winteri (Winteraceae) that exhibit antinociceptive properties. Since peripheral glutamate presents nociceptive actions, in this study it was investigated the effects of hydroalcooholic extracts from Drymis winteri (polygodial and drimanial) on the glutamatergic system in rat brain. Polygodial and drimanial inhibited glutamate uptake by astrocytes, as well as by cortical, hippocampal and striatal slices, and increased synaptosomal glutamate release...
March 2006: Neurochemical Research
Gregory D Leonard, Maurice A Wright, Mary G Quinn, Suzanne Fioravanti, Nancy Harold, Barbara Schuler, Rebecca R Thomas, Jean L Grem
BACKGROUND: New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. Oxaliplatin, an agent used in first-line therapy for metastatic colorectal cancer, causes acute and chronic neurotoxicity. This study was performed to carefully assess the incidence, type and duration of oxaliplatin neurotoxicity. METHODS: A detailed questionnaire was completed after each chemotherapy cycle for patients with metastatic colorectal cancer enrolled in a phase I trial of oxaliplatin and capecitabine...
2005: BMC Cancer
Orlando Ghirardi, Pietro Lo Giudice, Claudio Pisano, Mario Vertechy, Augusta Bellucci, Loredana Vesci, Sante Cundari, Mariarosaria Miloso, Laura Maria Rigamonti, Gabriella Nicolini, Claudio Zanna, Paolo Carminati
BACKGROUND: Oxaliplatin (OHP) is severely neurotoxic and induces the onset of a disabling sensory peripheral neuropathy. Acetyl-L-carnitine (ALC), a natural compound with neuroprotective action, was tested to determine whether it plays a protective role in OHP-induced neuropathy. MATERIALS AND METHODS: Peripheral neuropathy was induced in Wistar rats, and the effect of OHP alone or in combination with ALC was assessed, using behavioral and neurophysiological methods...
July 2005: Anticancer Research
Claudio Pisano, Graziella Pratesi, Diletta Laccabue, Franco Zunino, Pietro Lo Giudice, Augusta Bellucci, Licia Pacifici, Barbara Camerini, Loredana Vesci, Massimo Castorina, Sandra Cicuzza, Giovanni Tredici, Paola Marmiroli, Gabriella Nicolini, Stefania Galbiati, Menotti Calvani, Paolo Carminati, Guido Cavaletti
PURPOSE: Antineoplastic drugs belonging to platinum or taxane families are severely neurotoxic, inducing the onset of disabling peripheral neuropathies with different clinical signs. Acetyl-L-carnitine (ALC) is a natural occurring compound with a neuroprotective activity in several experimental paradigms. In this study we have tested the hypothesis that ALC may have a protective role on cisplatin and paclitaxel-induced neuropathy. EXPERIMENTAL DESIGN: Sensory nerve conduction velocity (SNCV) was measured in rats before, at end, and after an additional follow-up period from treatments with cisplatin, paclitaxel, or with the respective combination with ALC...
November 15, 2003: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Goran A Jamal, Stig Hansen, Peter O O Julu
A large number of published studies support the notion that long term, low level (LTLL) exposure to organophosphorus (OP) esters may cause neurological and neurobehavioral effects. In order to differentiate these from other effects of OP such as the acute cholinergic episodes, intermediate syndrome and organophosphate induced delayed neuropathy (OPIDN), the term Chronic Organophosphate Induced Neuropsychiatric Disorder (COPIND) will be used purely for the ease of reference. The question addressed in this particular review is whether LTLL exposure to OP may produce neurotoxicity...
December 27, 2002: Toxicology
A C Kuhlmann, T R Guilarte
The peripheral benzodiazepine receptor (PBR) is currently used as a marker of inflammation and gliosis following brain injury. Previous reports suggest that elevated PBR levels in injured brain tissue are specific to activated microglia and infiltrating macrophages. We have produced hippocampal lesions using the neurotoxicant trimethyltin (TMT) to examine the cellular and subcellular nature of the PBR response. Degenerating, argyrophilic pyramidal neurons were observed in the hippocampus at 2 and 14 days after TMT exposure...
April 2000: Journal of Neurochemistry
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