DOCSLIB.ORG

Large Amounts of Picolinic Acid Are Lethal but Small Amounts Increase the Conversion of Tryptophan-Nicotinamide in Rats

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Large Amounts of Picolinic Acid Are Lethal but Small Amounts Increase the Conversion of Tryptophan-Nicotinamide in Rats J Nutr Sci Vitaminol, 60, 334–339, 2014 Large Amounts of Picolinic Acid Are Lethal but Small Amounts Increase the Conversion of Tryptophan-Nicotinamide in Rats Katsumi SHIBATA and Tsutomu FUKUWATARI Department of Nutrition, School of Human Cultures, The University of Shiga Prefecture, Shiga 522–8533, Japan (Received May 13, 2014) Summary Picolinic acid (PiA) is an endogenous metabolite of tryptophan that has been reported to possess a wide range of physiological actions. We investigated the effects of dietary PiA on the metabolism of tryptophan to nicotinamide in growing rats. Feeding an ordinary diet containing 1% PiA to growing rats (6 wk) caused death within a few days. Toxicity of PiA was higher than that of analogs such as nicotinic acid and quinolinic acid. Feeding an ordinary diet containing 0.05% and 0.1% PiA did not elicit decreased intake of food or loss in body weight. PiA did not affect the in vitro liver activities of quinolinic acid phosphoribosyltransferase or a-amino-b-carboxymuconate-e-semialdehyde decarbox- ylase (ACMSDase, a Zn-dependent enzyme). Concentrations of NAD and NADP in the liver and blood were not affected by PiA. PiA administration did not affect tryptophan metabo- lites such as anthranilic acid, kynurenic acid, and xanthurenic acid. However, quinolinic acid and subsequent metabolites such as nicotinamide and its catabolites were increased by administration of a diet containing 0.05% PiA but not by a 0.1% PiA diet. These results suggest that the in vivo activity of ACMSDase is controlled by the Zn level. Therefore, a small amount of PiA has a beneficial effect for conversion of tryptophan to nicotinamide, but an excessive amount of PiA can be very toxic. Key Words picolinic acid, tryptophan, nicotinamide, toxicity, rat Picolinic acid (PiA) is a metabolite of the complete As in the case of QA, excessive amounts of nicotinic degradation pathway of tryptophan (Trp) (see, Fig. 1), acid, Nam, N1-methylnicotinic acid, and N1-methylnic- which has been reported to possess a wide range of otinamide (MNA) affect food intake and body-weight physiological actions (e.g., neuroprotective (1, 2) and gain only slightly (10). Administration of nicotinic acid immunological (3) effects) and zinc (Zn) metabolism (4). and Nam elicit a much greater increase in Nam catabo- PiA formation is controlled by the activities of two lites such as MNA, N1-methyl-2-pyridone-5-carbox- enzymes: a-amino-b-carboxymuconate-e-semialdehyde amide (2-Py) and N1-methyl-4-pyridone-3-carboxamide decarboxylase (ACMSDase) and a-aminomuconate-e- (4-Py). However, administration of MNA and N1-meth- semialdehyde dehydrogenase (AMSDHase). ACMSDase ylnicotinic acid do not produce increases in Nam catab- catalyzes the reaction of a-amino-b-carboxymuconate- olites (10). Whether dietary PiA affects the metabolism e-semialdehyde (ACMS) to a-aminomuconate-e-semial- of Trp to Nam is unknown. We investigated the effects dehyde (AMS) and AMSDHase the reaction of AMS to of dietary PiA on the growth, food intake, and metabo- 2-aminoadipic acid in the presence of NAD(P)H. lism of Trp to Nam in growing rats. PiA is created by non-enzymatic means from AMS. MATERIALS AND METHODS Quinolinic acid (QA) is produced non-enzymatically from ACMS, which is metabolized to nicotinic acid Chemicals. Vitamin-free milk casein, sucrose, and mononucleotide by QA phosphoribosyltransferase L-methionine were obtained from Wako Pure Chemical (QPRTase) in the presence of 5-phosphoribosyl 1-pyro- Industries, Ltd. (Osaka, Japan). Corn oil was purchased phosphate (PRPP). QA is the direct precursor of NAD in from Ajinomoto (Tokyo, Japan). Gelatinized cornstarch, the tryptophan (Trp)-nicotinamide (Nam) biosynthetic a mineral mixture (11), and a vitamin mixture (11) pathway, but dietary QA is not incorporated efficiently were purchased from Oriental Yeast Co., Ltd. (Tokyo, into NAD molecules (5). The low replacement efficiency Japan). PiA, anthranilic acid (AnA), QA and Nam were of QA for NAD is considered to result from inefficient obtained from Wako Pure Chemical Industries. MNA penetration of QA into cells (6–9). chloride, xanthurenic acid (XA), kynurenic acid (KA), The toxicity of QA is reported to be low. For exam- and 3-hydroxyanthranilic acid (3-HA) were purchased ple, feeding a diet containing 0.5% QA to weaning rats from Tokyo Chemical Industries (Tokyo, Japan). Com- affects food intake and body-weight gain slightly com- pounds 2-Py and 4-Py were synthesized according to pared with those of rats fed a non-QA control diet (10). the method of Pullman and Colowick (12) and that of Shibata et al. (13), respectively. All other chemicals were E-mail: [email protected] of the highest purity available from commercial sources. 334 Picolinic Acid and Tryptophan Metabolism 335 Fig. 1. Metabolic pathway of Trp. ACMS, a-amino-b-carboxymuconate-e-semialdehyde; AMS, a-aminomuconate-e-semi- aldehyde; NMN, nicotinamide mononucleotide. Table 1. Compositions of diets. 20% Casein diet 10.05% PiA 10.10% PiA 11.0% PiA g/kg diet Vitamin-free casein 200 200 200 200 L-Methionine 2 2 2 2 Gelatinized-cornstarch 464 463.5 463 454 Sucrose 224 224 224 224 Corn oil 50 50 50 50 Mineral mixture1 50 50 50 50 Vitamin mixture (NiA-free)1 10 10 10 10 PiA 0 0.5 1 10 1 Shibata K, Matsuo H. 1989. Effect of supplementing low protein diets with the limiting amino acids on the excretion of N1-methylnicotinamide and its pyridones in rats. J Nutr 119, 896–901. Animals and treatment. The care and treatment of and allowed to drink tap water ad libitum for 21 d; this experimental animals conformed to guidelines set by group was the control group (Table 1). The other groups The University of Shiga Prefecture (Shiga, Japan). The (n55) were fed the same diets with PiA addition (Table animal room was maintained at temperature of 22˚C 1) and allowed to drink tap water ad libitum for 21 d. and with 60% humidity. A 12-h light–dark cycle was The concentration of dietary PiA was selected from the also in operation (18:00–06:00). data about the toxicity of quinolinic acid (10) and nico- Six-week-old male Wistar rats obtained from CLEA tinic acid (10, 14). Urine samples (24 h; 09:00–09:00) Japan, Inc. (Tokyo, Japan) were housed individually in were collected at day 21 in amber bottles containing metabolic cages (CT-10; CLEA Japan). Rats were divided 1 mL of 1 mol/L HCl. Acidified urine samples were into four groups at 09:00, which was designated as stored at 225˚C until needed. After the last urine sam- the “zero time” of the experiment elapsed time. One ples had been collected, the rats were killed. Blood from group (n55) was fed a conventional 20% casein diet the carotid artery and the livers were removed, and were 336 SHIBATA K and FUKUWATARI T Fig. 2. Effects of dietary PiA on body-weight changes (A) and food intake (B) in rats. Values are mean6SE for 5 rats. Table 2. Effects of PiA on body weight, food intake, liver weight, NAD concentration and NADP concentration, and liver activities of QPRTase and ACMSDase in rats on day 21. 20% Casein diet 10.05% PiA 10.10% PiA Initial body weight, g 133.861.33 133.760.15 133.460.90 Final body weight, g 273.966.0 274.966.5 268.067.6 Body-weight gain, g/21 d 140.165.9 141.264.2 134.665.7 Total food intake, g/21 d 399610.8 392610.5 397613.6 Liver weight, g 12.2960.34 12.0760.48 11.9360.51 Liver NAD, nmol/g 826642.4 810633.7 824650.1 Liver NADP, nmol/g 43267.8 448637.5 437632.2 Blood NAD, nmol/mL 82.861.7 79.261.4 84.963.0 Blood NADP, nmol/mL 13.560.5 13.860.5 14.760.4 Liver QPRTase, nmol/h/g 1.1860.05 1.1560.04 1.1960.04 Liver ACMSDase, nmol/h/g 0.7460.11 0.9760.16 0.8660.13 Values are means6SE for 5 rats. Significant differences were not observed between values in rows. used for measurements of NAD and NADP as well as the Statistical analyses. Values are the mean6SE. Sig- enzyme activities of QPRTase and ACMSDase. nificance was determined by one-way ANOVA, followed Enzyme assays. The liver was dissected, and one by Tukey’s multiple-comparison test; p,0.05 was con- portion homogenized immediately with a Teflon-glass sidered significant. Prism version 5.0 (Graph Pad, San homogenizer in 5 volumes of cold 50 mmol/L KH2PO4– Diego, CA) was used for all analyses. K HPO buffer at pH 7.0. The resulting homogenate 2 4 RESULTS was used as an enzyme source. The methods of measuring of QPRTase (nicotinate Effects of a high-PiA diet on body weight and food intake nucleotide: pyrophosphate phosphoribosyltransferase, Body weights of rats fed the 1% PiA diet decreased by EC 2.4.2.19) (15) and ACMSDase (EC 4.1.1.45) (16) 1.9 g on day 1, and by 20 g on day 3. Three of the five have been reported previously. rats died on day 6, one rat on day 8, and one rat on day Measurement of Trp metabolites. Amounts of Trp 9. Rats ate 10 g of the 1% PiA diet on day 1, and 3 g/d metabolites such as AnA (17), KA (18), XA (19), 3-HA during days 2 to 5, but ate little after day 5. (19), QA (20), Nam (13), MNA (21), 2-Py (13), and Effects of low PiA on the metabolism of Trp to Nam 4-Py (13) in urine were measured by high-performance Feeding a diet containing low amounts of PiA (0.05% liquid chromatography.
Load more

Recommended publications
  • CHAPTER 29 ORGANIC CHEMICALS VI 29-1 Notes 1
    )&f1y3X CHAPTER 29 ORGANIC CHEMICALS VI 29-1 Notes 1. Except where the context otherwise requires, the headings of this chapter apply only to: (a) Separate chemically defined organic compounds, whether or not containing impurities; (b) Mixtures of two or more isomers of the same organic compound (whether or not containing impurities), except mixtures of acyclic hydrocarbon isomers (other than stereoisomers), whether or not saturated (chapter 27); (c) The products of headings 2936 to 2939 or the sugar ethers and sugar esters, and their salts, of heading 2940, or the products of heading 2941, whether or not chemically defined; (d) Products mentioned in (a), (b) or (c) above dissolved in water; (e) Products mentioned in (a), (b) or (c) above dissolved in other solvents provided that the solution constitutes a normal and necessary method of putting up these products adopted solely for reasons of safety or for transport and that the solvent does not render the product particularly suitable for specific use rather than for general use; (f) The products mentioned in (a), (b), (c), (d) or (e) above with an added stabilizer (including an anticaking agent) necessary for their preservation or transport; (g) The products mentioned in (a), (b), (c), (d), (e) or (f) above with an added antidusting agent or a coloring or odoriferous substance added to facilitate their identification or for safety reasons, provided that the additions do not render the product particularly suitable for specific use rather than for general use; (h) The following products, diluted to standard strengths, for the production of azo dyes: diazonium salts, couplers used for these salts and diazotizable amines and their salts.
    [Show full text]
  • Inventory Size (Ml Or G) 103220 Dimethyl Sulfate 77-78-1 500 Ml
    Inventory Bottle Size Number Name CAS# (mL or g) Room # Location 103220 Dimethyl sulfate 77-78-1 500 ml 3222 A-1 Benzonitrile 100-47-0 100ml 3222 A-1 Tin(IV)chloride 1.0 M in DCM 7676-78-8 100ml 3222 A-1 103713 Acetic Anhydride 108-24-7 500ml 3222 A2 103714 Sulfuric acid, fuming 9014-95-7 500g 3222 A2 103723 Phosphorus tribromide 7789-60-8 100g 3222 A2 103724 Trifluoroacetic acid 76-05-1 100g 3222 A2 101342 Succinyl chloride 543-20-4 3222 A2 100069 Chloroacetyl chloride 79-04-9 100ml 3222 A2 10002 Chloroacetyl chloride 79-04-9 100ml 3222 A2 101134 Acetyl chloride 75-36-5 500g 3222 A2 103721 Ethyl chlorooxoacetate 4755-77-5 100g 3222 A2 100423 Titanium(IV) chloride solution 7550-45-0 100ml 3222 A2 103877 Acetic Anhydride 108-24-7 1L 3222 A3 103874 Polyphosphoric acid 8017-16-1 1kg 3222 A3 103695 Chlorosulfonic acid 7790-94-5 100g 3222 A3 103694 Chlorosulfonic acid 7790-94-5 100g 3222 A3 103880 Methanesulfonic acid 75-75-2 500ml 3222 A3 103883 Oxalyl chloride 79-37-8 100ml 3222 A3 103889 Thiodiglycolic acid 123-93-3 500g 3222 A3 103888 Tetrafluoroboric acid 50% 16872-11-0 1L 3222 A3 103886 Tetrafluoroboric acid 50% 16872-11-0 1L 3222 A3 102969 sulfuric acid 7664-93-9 500 mL 2428 A7 102970 hydrochloric acid (37%) 7647-01-0 500 mL 2428 A7 102971 hydrochloric acid (37%) 7647-01-0 500 mL 2428 A7 102973 formic acid (88%) 64-18-6 500 mL 2428 A7 102974 hydrofloric acid (49%) 7664-39-3 500 mL 2428 A7 103320 Ammonium Hydroxide conc.
    [Show full text]
  • United States Patent (19) (11 Patent Number: 4859,592 Hagedorn Et Al
    United States Patent (19) (11 Patent Number: 4859,592 Hagedorn et al. 45 Date of Patent: Aug. 22, 1989 54 PRODUCTION OF PICOL.INIC ACID AND OTHER PUBLICATIONS PYRIDINE PRODUCTS VIA PSEUDOMONAS Dagley, et al., "New Pathways in the Oxidative Metab olism of Aromatic Compounds by Micro-Organisms'; (76 Inventors: Scott R. Hagedorn, Old Coach Rd., Summit, N.J. 07087; Anthony J. East, Nature, V. 188, pp. 560-566 (1960). 63 Niles Ave., Madison, N.J. O7940; Moser et al., “Decarboxylation of 5-Sub Sol J. Barer, 271 White Oak Ridge stituted-2-Pyridinecarboxylic Acids', J. Org. Chem., Rd., Bridgewater, N.J. 08807 V. 37, No. 24, pp. 3938-3940 (1972). Primary Examiner-Elizabeth C. Weimar 21) Appl. No.: 759,038 Attorney, Agent, or Firm-Mathews, Woodbridge, 22 Filed: Jul. 26, 1985 Goebel, Pugh & Collins (51) Int. Cl." ........................ C12P 17/12; C12N 1/20; (57) ABSTRACT C12R 1/40 (52) U.S. Cl. ................................. 435/122; 435/253.3; This invention provides a process for the bioconversion 435/877 of a non-growth aromatic feed to an accumulated quan tity of a picolinic acid product with reduced accumula (58) Field of Search ............. 435/122, 253, 877, 253.3 tion of 2-hydroxymuconic semialdehyde, and con 56 References Cited ducted in the presence of ammonium or a primary U.S. PATENT DOCUMENTS amine, which acid subsequently can be converted by 4,654,303 3/1987 Hagedorn ......................... 435/1723 chemical means to a pyridine product. 4,666,841 5/1987 Hagedorn ... ... 435/122 4,673,646 6/1987 Hagedorn ............ was sex as a was u + 435/146 6 Claims, 2 Drawing Sheets U.S.
    [Show full text]
  • Metabotropic Glutamate Receptors
    mGluR Metabotropic glutamate receptors mGluR (metabotropic glutamate receptor) is a type of glutamate receptor that are active through an indirect metabotropic process. They are members of thegroup C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatoryneurotransmitter. The mGluRs perform a variety of functions in the central and peripheral nervous systems: mGluRs are involved in learning, memory, anxiety, and the perception of pain. mGluRs are found in pre- and postsynaptic neurons in synapses of the hippocampus, cerebellum, and the cerebral cortex, as well as other parts of the brain and in peripheral tissues. Eight different types of mGluRs, labeled mGluR1 to mGluR8, are divided into groups I, II, and III. Receptor types are grouped based on receptor structure and physiological activity. www.MedChemExpress.com 1 mGluR Agonists, Antagonists, Inhibitors, Modulators & Activators (-)-Camphoric acid (1R,2S)-VU0155041 Cat. No.: HY-122808 Cat. No.: HY-14417A (-)-Camphoric acid is the less active enantiomer (1R,2S)-VU0155041, Cis regioisomer of VU0155041, is of Camphoric acid. Camphoric acid stimulates a partial mGluR4 agonist with an EC50 of 2.35 osteoblast differentiation and induces μM. glutamate receptor expression. Camphoric acid also significantly induced the activation of NF-κB and AP-1. Purity: ≥98.0% Purity: ≥98.0% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 100 mg Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg (2R,4R)-APDC (R)-ADX-47273 Cat. No.: HY-102091 Cat. No.: HY-13058B (2R,4R)-APDC is a selective group II metabotropic (R)-ADX-47273 is a potent mGluR5 positive glutamate receptors (mGluRs) agonist.
    [Show full text]
  • Control of Growth by Picolinic Acid
    Proc. Nati. Acad. Sci. USA Vol. 74, No. 7, pp. 2889-2893, July 1977 Cell Biology Control of growth by picolinic acid: Differential response of normal and transformed cells (cell synchrony/chelating agents/NAD+/pyridine derivatives/viral transformation) J. A. FERNANDEZ-POL*t, VINCENT H. BONO, JR.J, AND GEORGE S. JOHNSON* * Laboratory of Molecular Biology and * Laboratory of Medicinal Chemistry and Biology, National Cancer Institute, Bethesda, Maryland 20014 Communicated by Nathan 0. Kaplan, April 14, 1977 ABSTRACT Picolinic acid reversibly inhibits the growth under 95% air/5% CO2, humidified atmosphere, at 37°. The of cultured cells. Fourteen other pyridine derivatives were in- cell lines used are listed in Table 1. Unless otherwise indicated, effective or toxic. Untransformed normal rat kidney (NRK) cells cells were planted at 1.5 X 105 cells per dish. Twenty-four hours are reversibly arrested in the G1 stage of the growth cycle as later, media were replaced by new media with or shown by cell counts, mitotic index, [3H]thymidine incorpora- (treated) tion, and flow microfluorometry. Flow microfluorometry was without (control) picolinic acid. All cells lines were treated with used to monitor the effects of picolinic acid on numerous other picolinic acid at 1.5,2,2.5,3, and 4 mM and analyzed for 4 days cell lines. Normal cells are blocked in GI, whereas transformed with media change every other day. cells show responses that are dependent upon the transforming Cells were analyzed for DNA content by flow microfluo- virus and independent of species or origin of the cell line. Kir- rometry (FMF) after trypsinization and suspension in pro- sten sarcoma virus-transformed cells are blocked in GI.
    [Show full text]
  • The Breakdown of Pyruvate by Cell-Free Extracts of the Rumen Micro-Organism LC
    Vol. 74 METABOLISM OF XANTHURENIC ACID 525 with acid; no direct proof, however, is given that that the hydroxyl group in position 8 is bound to this transformation is brought about by detach- glucuronic acid. ment of a glucuronic residue from the hydroxyl group in position 4 of xanthurenic acid. The fact The authors are grateful to Professor Benassi of the that the R. values of Rothstein & Greenberg's Institute of Pharmaceutical Chemistry of the University of compounds B and D in butanol-acetic acid-water Padova for a kind gift of a sample of 8-methylxanthurenic (4:1:5) differ from those of our compounds indicate acid ethyl ester. that they are not the same substances. The differ- REFERENCES ence might tentatively be ascribed to the fact that xanthurenic acid can be conjugated in the living Baglioni, C., Fasella, P., Turano, C. & Siliprandi, N. (1960). organism in several ways and that differences exist G. Biochim. (in the Press). not only between various species, e.g. the rabbit Block, R. J. & Boiling, D. (1951). The Aminoacid Compo8i- and the rat (Rothstein & Greenberg, 1957), but tion of Protein and Foods, p. 413. Springfield, Mass.: also between different races of the same C. Thomas. species. Consden, R., Gordon, A. H. & Martin, A. J. P. (1944). Biochem. J. 38, 224. SUMMARY Dalglesh, C. E. (1952). Biochem. J. 52, 3. Dalgliesh, C. E. (1955). J. clin. Path. 8, 73. 1. Two major metabolites of xanthurenic acid Daigliesh, C. E. (1956). Biochem. J. 64, 481. were found in the urine of albino rats after intra- Dent, C.
    [Show full text]
  • Neurotransmitters-Sample-Report
    Neurotransmitters Test the messengers of your neural network 1(866) 364-0963 www.vibrant-wellness.com 1360 Bayport Ave. Ste. B [email protected] San Carlos, CA 94070 Neurotransmitters Vibrant Wellness | 1360 Bayport Ave, Ste B. San Carlos, CA 94070 1(866) 364-0963 | [email protected] | www. vibrant-wellness.com Final Report Date: 06-19-2020 16:03 Specimen Collected: 06-18-2020 16:03 Accession ID: 2006190275 Specimen Received: 06-19-2020 10:03 LAST NAME FIRST NAME GENDER DATE OF BIRTH ACCESSION ID DATE OF SERVICE PATIENT TEST2 MALE 1998-01-06 2006190275 06-18-2020 16:03 PATIENT PROVIDER Name: TEST2 PATIENT Practice Name: Vibrant IT4 Practice Date of Birth: 1998-01-06 Provider Name: Demo Client, DDD (999994) Gender: Male Street Address: TEST STREET Age: 22 City: TEST CITY State: KY Fasting: FASTING Zip #: 42437 Telephone #: Fax #: 000-000-0000 Vibrant Wellness is pleased to present to you, 'Neurotransmitters', to help you make healthy lifestyle, dietary and treatment choices in consultation with your healthcare provider. It is intended to be used as a tool to encourage a general state of health and well-being. The Vibrant Neurotransmitters is a test to measure inhibitory, excitatory and other neurotransmitters . The panel is designed to give a complete picture of an individual’s levels of neurotransmitters in urine. Interpretation of Report: The report contains the complete list of the all urine neurotransmitters tested with quantitative results to enable a full overview along with the corresponding reference ranges. The classification of Red indicates a result that is outside the reference range and the classification of Green denotes a result that is within the reference range.
    [Show full text]
  • The Effect of Rosmarinic Acid on Apoptosis and Nnos Immunoreactivity Following Intrahippocampal Kainic Acid Injections in Rats
    Basic and Clinical January, February 2020, Volume 11, Number 1 Research Paper: The Effect of Rosmarinic Acid on Apoptosis and nNOS Immunoreactivity Following Intrahippocampal Kainic Acid Injections in Rats Safoura Khamse1* , Seyed Shahabeddin Sadr1,2 , Mehrdad Roghani3* , Mina Rashvand1 , Maryam Mohammadian4 , Narges Mare- fati1 , Elham Harati1 , Fatemeh Ebrahimi1 1. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. 3. Neurophysiology Research Center, Shahed University, Tehran, Iran. 4. Department of Physiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Use your device to scan and read the article online Citation: Khamse, S., Sadr, Sh., Roghani, M., Rashvand, M., Mohammadian, M., & Marefati, N., et al. The Effect of Ros- marinic Acid on Apoptosis and nNOS Immunoreactivity Following Intrahippocampal Kainic Acid Injections in Rats Basic and Clinical Neuroscience, 11(1), 41-48. http://dx.doi.org/10.32598/bcn.9.10.340 http://dx.doi.org/10.32598/bcn.9.10.340 A B S T R A C T Introduction: Kainic Acid (KA) is an ionotropic glutamate receptor agonist. KA can induce neuronal overactivity and excitotoxicity. Rosmarinic Acid (RA) is a natural polyphenolic Article info: compound with antioxidant, anti-apoptotic, anti-neurodegenerative, and anti-inflammatory Received: 12 Apr 2018 properties. This study aimed to assess the effect of RA on apoptosis, nNOS-positive neurons First Revision: 10 May 2018 number, as well as Mitogen-Activated Protein Kinase (MAPK) and Cyclooxygenase-2 (COX- Accepted: 27 Oct 2018 2) immunoreactivity, following intrahippocampal Kainic acid injection in rats.
    [Show full text]
  • Chemical Products
    CUSTOM MANUFACTURING AND FINE CHEMICAL SOURCING 768 N. Bethlehem Pike ⚫ Lower Gwynedd, PA 19002 USA Tel: (215) 628-2946 ⚫ Fax: (215) 628-4262 ⚫ Web: www.richmanchemical.com Chemical Products This is a representative list of products which Richman Chemical Inc. supplied, sourced for our customers, or custom manufactured. This partial list shows only what we have done in the past, and it may not include what we are capable of doing for you. Therefore, if you are looking for a specific material not on our list, please call with your inquiry. Satisfying your unique or special needs is our full time business.
    [Show full text]
  • Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity
    fnins-14-00620 June 27, 2020 Time: 15:13 # 1 REVIEW published: 24 June 2020 doi: 10.3389/fnins.2020.00620 Kynurenine and Tetrahydrobiopterin Pathways Crosstalk in Pain Hypersensitivity Ananda Staats Pires1,2, Vanessa X. Tan1, Benjamin Heng1, Gilles J. Guillemin1* and Alexandra Latini2* 1 Neuroinflammation Group, Department of Biomedical Sciences, Centre for Motor Neuron Disease Research, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia, 2 Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil Despite the identification of molecular mechanisms associated with pain persistence, no Edited by: significant therapeutic improvements have been made. Advances in the understanding Marianthi Papakosta, of the molecular mechanisms that induce pain hypersensitivity will allow the Takeda Pharmaceutical Company Limited, United States development of novel, effective, and safe therapies for chronic pain. Various pro- Reviewed by: inflammatory cytokines are known to be increased during chronic pain, leading Wladyslaw-Lason, to sustained inflammation in the peripheral and central nervous systems. The Institute of Pharmacology (PAS), Poland pro-inflammatory environment activates additional metabolic routes, including the Ewa Krystyna kynurenine (KYN) and tetrahydrobiopterin (BH4) pathways, which generate bioactive Szczepanska-Sadowska, soluble metabolites with the potential to modulate neuropathic and inflammatory pain Medical University of Warsaw, Poland sensitivity. Inflammation-induced upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) *Correspondence: Gilles J. Guillemin and guanosine triphosphate cyclohydrolase I (GTPCH), both rate-limiting enzymes [email protected] of KYN and BH4 biosynthesis, respectively, have been identified in experimental Alexandra Latini [email protected] chronic pain models as well in biological samples from patients affected by chronic pain.
    [Show full text]
  • Kainic Acid-Induced Neurotoxicity: Targeting Glial Responses and Glia-Derived Cytokines
    388 Current Neuropharmacology, 2011, 9, 388-398 Kainic Acid-Induced Neurotoxicity: Targeting Glial Responses and Glia-Derived Cytokines Xing-Mei Zhang1 and Jie Zhu1,2, 1Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; 2Department of Neurology, The First Hospital of Jilin University, Changchun, China Abstract: Glutamate excitotoxicity contributes to a variety of disorders in the central nervous system, which is triggered primarily by excessive Ca2+ influx arising from overstimulation of glutamate receptors, followed by disintegration of the endoplasmic reticulum (ER) membrane and ER stress, the generation and detoxification of reactive oxygen species as well as mitochondrial dysfunction, leading to neuronal apoptosis and necrosis. Kainic acid (KA), a potent agonist to the -amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate class of glutamate receptors, is 30-fold more potent in neuro- toxicity than glutamate. In rodents, KA injection resulted in recurrent seizures, behavioral changes and subsequent degeneration of selective populations of neurons in the brain, which has been widely used as a model to study the mechanisms of neurode- generative pathways induced by excitatory neurotransmitter. Microglial activation and astrocytes proliferation are the other characteristics of KA-induced neurodegeneration. The cytokines and other inflammatory molecules secreted by activated glia cells can modify the outcome of disease progression. Thus, anti-oxidant and anti-inflammatory treatment could attenuate or prevent KA-induced neurodegeneration. In this review, we summarized updated experimental data with regard to the KA-induced neurotoxicity in the brain and emphasized glial responses and glia-oriented cytokines, tumor necrosis factor-, interleukin (IL)-1, IL-12 and IL-18.
    [Show full text]
  • Nutritional and Herbal Therapies for Children and Adolescents
    Nutritional and Herbal Therapies for Children and Adolescents A Handbook for Mental Health Clinicians Nutritional and Herbal Therapies for Children and Adolescents A Handbook for Mental Health Clinicians George M. Kapalka Associate Professor, Monmouth University West Long Branch, NJ and Director, Center for Behavior Modifi cation Brick, NJ AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 32 Jamestown Road, London NW1 7BY, UK 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, CA 92101-4495, USA Copyright © 2010 Elsevier Inc. All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher. Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (44) (0) 1865 843830; fax (44) (0) 1865 853333; email: [email protected]. Alternatively, visit the Science and Technology Books website at www.elsevierdirect.com/rights for further information Notice No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material
    [Show full text]