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Pernilla Videhult Pierre, Jakob Haglöf, Birgitta Linder, Mikael K R Engskog, Torbjörn Arvidsson, Curt Pettersson, Anette Fransson, Göran Laurell
BACKGROUND: Ototoxicity from treatment with the anticancer drug cisplatin remains a clinical problem. A wide range of intracellular targets of cisplatin has been found in vivo. AIM: To investigate cisplatin-induced change of the serum metabolite profile and its association with ototoxicity. MATERIAL AND METHODS: Guinea pigs (n = 14) were treated with cisplatin (8 mg/kg b.w., i.v.) 30 min after administration of the otoprotector candidate sodium thiosulfate (group STS; n = 7) or sodium chloride (group NaCl; n = 7)...
October 2017: Acta Oto-laryngologica
Serena Notartomaso, Giada Mascio, Matteo Bernabucci, Cristina Zappulla, Pamela Scarselli, Milena Cannella, Tiziana Imbriglio, Roberto Gradini, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti
Background L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results A seven-day treatment with L-acetylcarnitine (100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain...
January 2017: Molecular Pain
Meng Yu, Hong-Mei Jia, Feng-Xia Cui, Yong Yang, Yang Zhao, Mao-Hua Yang, Zhong-Mei Zou
Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)...
March 10, 2017: International Journal of Molecular Sciences
Haonan Zhou, Pengjie Zhang, Zhiguo Hou, Jiabin Xie, Yuming Wang, Bin Yang, Yanyan Xu, Yubo Li
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances...
November 25, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Salman A Alotaibi, Abdulrazaq Alanazi, Saleh A Bakheet, Naif O Alharbi, Mahmoud N Nagi
Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen-induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes...
January 2016: Journal of Biochemical and Molecular Toxicology
Evan L Pannkuk, Evagelia C Laiakis, Simon Authier, Karen Wong, Albert J Fornace
Due to concerns surrounding potential large-scale radiological events, there is a need to determine robust radiation signatures for the rapid identification of exposed individuals, which can then be used to guide the development of compact field deployable instruments to assess individual dose. Metabolomics provides a technology to process easily accessible biofluids and determine rigorous quantitative radiation biomarkers with mass spectrometry (MS) platforms. While multiple studies have utilized murine models to determine radiation biomarkers, limited studies have profiled nonhuman primate (NHP) metabolic radiation signatures...
August 2015: Radiation Research
Sarah E Seiler, Timothy R Koves, Jessica R Gooding, Kari E Wong, Robert D Stevens, Olga R Ilkayeva, April H Wittmann, Karen L DeBalsi, Michael N Davies, Lucas Lindeboom, Patrick Schrauwen, Vera B Schrauwen-Hinderling, Deborah M Muoio
Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise...
July 7, 2015: Cell Metabolism
José-Ramón Rueda, Virginia Guillén, Javier Ballesteros, Maria-Isabel Tejada, Ivan Solà
BACKGROUND: People with fragile X syndrome (FXS) have an intellectual dysfunction that can range from very mild to severe. Symptoms can include speech and language delays and behavioural difficulties such as aggression or self injurious behaviours, emotional lability, and anxiety-related problems (for example obsessive-compulsive symptoms and perseverative behaviours). In some cases, affected people may have an additional diagnosis of attention deficit hyperactivity disorder or an autism spectrum disorder...
2015: Cochrane Database of Systematic Reviews
Federica Ferrari, Antonella Gorini, Roberto Federico Villa
Synaptic energy state and mitochondrial dysfunction are crucial factors in many brain pathologies. l-acetylcarnitine, a natural derivative of carnitine, improves brain energy metabolism, and has been proposed for the Therapy of many neurological and psychiatric diseases. The effects of the drug on the maximum rate (Vmax) of enzymatic activities related to hippocampal synaptic energy utilization were evaluated, in the perspective of its employment for Dementias and Depression Therapy. Two types of synaptic plasma membranes (SPM1 and SPM2) were isolated from the hippocampus of rats treated with l-acetylcarnitine (30 and 60mg/kg i...
June 5, 2015: European Journal of Pharmacology
Brian R Holder, Colleen A McNaney, David Luchetti, Eric Schaeffer, Dieter M Drexler
Acetyl-L-carnitine (ALCAR) is a potential biomarker for the modulation of brain neurotransmitter activity, but is also present in cerebrospinal fluid (CSF). Recent studies have utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) based assays to detect and quantify ALCAR within biofluids such as urine, plasma and serum, using various sample pretreatment procedures. In order to address the need to quantify ALCAR in CSF on a high-throughput scale, a new and simple HILIC-MS/MS assay has been successfully developed and validated...
September 2015: Biomedical Chromatography: BMC
Janos Kerner, Elizabeth Yohannes, Kwangwon Lee, Ashraf Virmani, Aleardo Koverech, Claudio Cavazza, Mark R Chance, Charles Hoppel
Previously we showed that in vivo treatment of elderly Fisher 344 rats with acetylcarnitine abolished the age-associated defect in respiratory chain complex III in interfibrillar mitochondria and improved the functional recovery of the ischemic/reperfused heart. Herein, we explored mitochondrial protein acetylation as a possible mechanism for acetylcarnitine's effect. In vivo treatment of elderly rats with acetylcarnitine restored cardiac acetylcarnitine content and increased mitochondrial protein lysine acetylation and increased the number of lysine-acetylated proteins in cardiac subsarcolemmal and interfibrillar mitochondria...
January 2015: Mechanisms of Ageing and Development
Michael S Dodd, Helen J Atherton, Carolyn A Carr, Daniel J Stuckey, James A West, Julian L Griffin, George K Radda, Kieran Clarke, Lisa C Heather, Damian J Tyler
BACKGROUND: Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. METHODS AND RESULTS: Using hyperpolarized carbon-13 ((13)C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats...
November 2014: Circulation. Cardiovascular Imaging
Yue-Tao Liu, Jing-Bo Peng, Hong-Mei Jia, Da-Yong Cai, Hong-Wu Zhang, Chang-Yuan Yu, Zhong-Mei Zou
Xin-Ke-Shu (XKS), a patent traditional Chinese medicine (TCM) preparation, has been commonly used for the treatment of coronary heart disease in China. In order to understand its mechanism of action, a metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) was utilized to profile the plasma metabolic fingerprints of atherosclerosis (AS) rabbits with and without XKS treatment. The metabolic profile of model group clearly separated from normal, and that of XKS group was closer to the control group...
September 25, 2014: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Junfang Wu, Jie Niu, Xiaopeng Li, Xianwei Wang, Zhikun Guo, Fenxi Zhang
BACKGROUND: Bone marrow derived mesenchymal stem cells (bmMSCs) are multipotent cells that can differentiate into diverse cell types, including cardiomyocytes. BmMSC-based transplantation is capable of repairing acute and chronic myocardial infarction. Prior to the transplantation, MSCs are usually induced in vitro by biological reagents and chemicals for directional differentiation. Transforming growth factor beta (TGF-β) is one of the most commonly used biological reagents for induction of cardiomyocyte differentiation of bmMSCs...
May 18, 2014: BMC Developmental Biology
Yasuro Furuichi, Naoko Goto-Inoue, Yasuko Manabe, Mitsutoshi Setou, Kazumi Masuda, Nobuharu L Fujii
Carnitine is well recognized as a key regulator of long-chain fatty acyl group translocation into the mitochondria. In addition, carnitine, as acetylcarnitine, acts as an acceptor of excess acetyl-CoA, a potent inhibitor of pyruvate dehydrogenase. Here, we provide a new methodology for accurate quantification of acetylcarnitine content and determination of its localization in skeletal muscles. We used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to visualize acetylcarnitine distribution in rat skeletal muscles...
October 2014: Biochimica et Biophysica Acta
M Besouw, E Cornelissen, D Cassiman, L Kluijtmans, L van den Heuvel, E Levtchenko
BACKGROUND: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequate correction of plasma carnitine...
2014: JIMD Reports
Enrica Bianchi, Lorenzo Di Cesare Mannelli, Cristina Menicacci, Paola Lorenzoni, Margherita Aglianò, Carla Ghelardini
AIMS: in the present study, our aim was to validate in vivo the prophylactic role of acetyl-l-carnitine (ALC) using an established knee osteoarthritis (OA) animal model which mimics the pathological changes of OA in humans, targeting cartilage and causing chondrocyte death. MAIN METHODS: animal model was obtained by an intra-articular injection of monosodium iodoacetate (MIA) into rat femorotibial joint space. Pain was measured in animals submitted to MIA model by paw pressure and compression behavioral tests in the presence or absence of ALC...
June 13, 2014: Life Sciences
Jie Zhang, Zhenzhen Huang, Minjian Chen, Yankai Xia, Francis L Martin, Wei Hang, Heqing Shen
OBJECTIVE: To identify the differential urinary metabolic pattern of oligozoospermic infertile men and to determine the potential biomarkers indicative of infertility. DESIGN: Observational study. SETTING: University hospital. PATIENT(S): Totals of 158 fertile volunteers and 135 oligozoospermic infertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary metabolic profiles were acquired with the use of liquid chromatography/mass spectrometry...
July 2014: Fertility and Sterility
Evagelia C Laiakis, Tytus D Mak, Sebastien Anizan, Sally A Amundson, Christopher A Barker, Suzanne L Wolden, David J Brenner, Albert J Fornace
The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4-6 h postirradiation (a single dose of 1...
April 2014: Radiation Research
Sugiharto Sugiharto, Mette S Hedemann, Charlotte Lauridsen
BACKGROUND: The processes of weaning and exposure to pathogenic bacteria induce stress responses, which may alter the metabolism. In this study, we investigated the changes in plasma metabolites and immune responses in piglets in response to the stress induced by weaning and Escherichia coli challenge. RESULTS: Fecal dry matter decreased (P = 0.003) and nearly half (44.4%) the piglets developed diarrhea on day 2 and 3 postweaning. The concentration of plasma immunoglobulin A was higher (P < 0...
2014: Journal of Animal Science and Biotechnology
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