Abstract
Systemic administration of 3-nitropropionic acid (3-NPA) is commonly used to induce Huntington’s disease (HD)-like symptoms in experimental animals. Here, the potential neuroprotective efficiency of rutin and selenium (RSe) co-administration on 3-NPA-induced HD-like symptoms model in mice was investigated. 3-NPA injection evoked severe alterations in redox status, as indicated via increased striatal malondialdehyde and nitric oxide levels, accompanied by a decrease in levels of antioxidant molecules including glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Moreover, 3-NPA potentiated inflammatory status by enhancing the production of interleukin-1β, tumor necrosis factor-α, and myeloperoxidase activity. Pro-apoptotic cascade was also recorded in the striatum as evidenced through upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. 3-NPA activated astrocytes as indicated by the upregulated glial fibrillary acidic protein and inhibited brain-derived neurotrophic factor. Furthermore, perturbations in cholinergic and monoaminergic systems were observed. RSe provided neuroprotective effects by preventing body weight loss, oxidative stress, neuroinflammation, and the apoptotic cascade. RSe inhibited the activation of astrocytes, increased brain-derived neurotrophic factor, and improved cholinergic and monoaminergic transmission following 3-NPA intoxication. Taken together, RSe co-administration may prevent or delay the progression of HD and its associated impairments through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory effects.
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Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Ahmed LA, Darwish HA, Abdelsalam RM, Amin HA (2016) Role of rho kinase inhibition in the protective effect of fasudil and simvastatin against 3-nitropropionic acid-induced striatal neurodegeneration and mitochondrial dysfunction in rats. Mol Neurobiol 53:3927–3938. https://doi.org/10.1007/s12035-015-9303-2
Almeer RS, Kassab RB, AlBasher GI, Alarifi S, Alkahtani S, Ali D, Abdel Moneim AE (2018) Royal jelly mitigates cadmium-induced neuronal damage in mouse cortex. Mol Biol Rep 46:119–131. https://doi.org/10.1007/s11033-018-4451-x
Annapurna A, Ansari MA, Manjunath PM (2013) Partial role of multiple pathways in infarct size limiting effect of quercetin and rutin against cerebral ischemia-reperfusion injury in rats. Eur Rev Med Pharmacol Sci 17:491–500
Bortolatto CF, Jesse CR, Wilhelm EA, Chagas PM, Nogueira CW (2013) Organoselenium bis selenide attenuates 3-nitropropionic acid-induced neurotoxicity in rats. Neurotox Res 23:214–224. https://doi.org/10.1007/s12640-012-9336-5
Cardoso BR, Roberts BR, Bush AI, Hare DJ (2015) Selenium, selenoproteins and neurodegenerative diseases. Metallomics 7:1213–1228. https://doi.org/10.1039/c5mt00075k
Chen JY, Wang EA, Cepeda C, Levine MS (2013) Dopamine imbalance in Huntington’s disease: a mechanism for the lack of behavioral flexibility. Front Neurosci 7:114. https://doi.org/10.3389/fnins.2013.00114
Dalla Corte CL, Bastos LL, Dobrachinski F, Rocha JB, Soares FA (2012) The combination of organoselenium compounds and guanosine prevents glutamate-induced oxidative stress in different regions of rat brains. Brain Res 1430:101–111. https://doi.org/10.1016/j.brainres.2011.10.049
Dhadde SB, Nagakannan P, Roopesh M, Anand Kumar SR, Thippeswamy BS, Veerapur VP, Badami S (2016) Effect of embelin against 3-nitropropionic acid-induced Huntington's disease in rats. Biomed Pharmacother 77:52–58. https://doi.org/10.1016/j.biopha.2015.11.009
Domitrovic R et al (2012) Differential hepatoprotective mechanisms of rutin and quercetin in CCl(4)-intoxicated BALB/cN mice. Acta Pharmacol Sin 33:1260–1270. https://doi.org/10.1038/aps.2012.62
Donato F, de Gomes MG, Goes AT, Seus N, Alves D, Jesse CR, Savegnago L (2013) Involvement of the dopaminergic and serotonergic systems in the antidepressant-like effect caused by 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole. Life Sci 93:393–400. https://doi.org/10.1016/j.lfs.2013.07.024
Drury RAB, Wallington EA (1980) Preparation and fixation of tissues. In: Carleton’s Histological Technique, 5th edn. Oxford University Press, New York pp 41–54
D'Souza GX, Waldvogel HJ (2016) Targeting the cholinergic system to develop a novel therapy for Huntington’s disease. J Huntington's Dis 5:333–342. https://doi.org/10.3233/JHD-160200
Duran-Vilaregut J, Manich G, del Valle J, Pallas M, Camins A, Pelegri C, Vilaplana J (2011) Neuronal apoptosis in the striatum of rats treated with 3-nitropropionic acid is not triggered by cell-cycle re-entry. Neurotoxicology 32:734–741. https://doi.org/10.1016/j.neuro.2011.07.009
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Enogieru AB, Haylett W, Hiss DC, Bardien S, Ekpo OE (2018) Rutin as a potent antioxidant: implications for neurodegenerative disorders. Oxidative Med Cell Longev 2018:6241017. https://doi.org/10.1155/2018/6241017
Farias JG, Puebla M, Acevedo A, Tapia PJ, Gutierrez E, Zepeda A, Calaf G, Juantok C, Reyes JG (2010) Oxidative stress in rat testis and epididymis under intermittent hypobaric hypoxia: protective role of ascorbate supplementation. J Androl 31:314–321. https://doi.org/10.2164/jandrol.108.007054
Fernandez SP, Wasowski C, Loscalzo LM, Granger RE, Johnston GA, Paladini AC, Marder M (2006) Central nervous system depressant action of flavonoid glycosides. Eur J Pharmacol 539:168–176. https://doi.org/10.1016/j.ejphar.2006.04.004
Frank S (2014) Treatment of Huntington’s disease. Neurotherapeutics 11:153–160. https://doi.org/10.1007/s13311-013-0244-z
Gautam R, Singh M, Gautam S, Rawat JK, Saraf SA, Kaithwas G (2016) Rutin attenuates intestinal toxicity induced by methotrexate linked with anti-oxidative and anti-inflammatory effects. BMC Complement Altern Med 16:99. https://doi.org/10.1186/s12906-016-1069-1
Gilbert GJ (2009) Weight loss in Huntington disease increases with higher CAG repeat number. Neurology 73:572; author reply 572. https://doi.org/10.1212/WNL.0b013e3181af0cf4
Gopinath K, Sudhandiran G (2016) Protective effect of naringin on 3-nitropropionic acid-induced neurodegeneration through the modulation of matrix metalloproteinases and glial fibrillary acidic protein. Can J Physiol Pharmacol 94:65–71. https://doi.org/10.1139/cjpp-2015-0035
Heinrikson RL, Meredith SC (1984) Amino acid analysis by reverse-phase high-performance liquid chromatography: precolumn derivatization with phenylisothiocyanate. Anal Biochem 136:65–74
Hsiao HY, Chen YC, Chen HM, Tu PH, Chern Y (2013) A critical role of astrocyte-mediated nuclear factor-kappaB-dependent inflammation in Huntington's disease. Hum Mol Genet 22:1826–1842. https://doi.org/10.1093/hmg/ddt036
Jamwal S, Kumar P (2017) L-theanine, a component of green tea prevents 3-nitropropionic acid (3-NP)-induced striatal toxicity by modulating nitric oxide pathway. Mol Neurobiol 54:2327–2337. https://doi.org/10.1007/s12035-016-9822-5
Kassab RB, Lokman MS, Essawy EA (2018) Neurochemical alterations following the exposure to di-n-butyl phthalate in rats. Metab Brain Dis 34:235–244. https://doi.org/10.1007/s11011-018-0341-0
Kaur N, Jamwal S, Deshmukh R, Gauttam V, Kumar P (2015) Beneficial effect of rice bran extract against 3-nitropropionic acid induced experimental Huntington’s disease in rats. Toxicol Rep 2:1222–1232. https://doi.org/10.1016/j.toxrep.2015.08.004
Khan HA (2010) Selenium partially reverses the depletion of striatal dopamine and its metabolites in MPTP-treated C57BL mice. Neurochem Int 57:489–491. https://doi.org/10.1016/j.neuint.2010.06.020
Khan A, Jamwal S, Bijjem KR, Prakash A, Kumar P (2015) Neuroprotective effect of hemeoxygenase-1/glycogen synthase kinase-3beta modulators in 3-nitropropionic acid-induced neurotoxicity in rats. Neuroscience 287:66–77. https://doi.org/10.1016/j.neuroscience.2014.12.018
Koc S, Cayli S, Aksakal C, Ocakli S, Soyalic H, Somuk BT, Yuce S (2016) Protective effects of melatonin and selenium against apoptosis of olfactory sensory neurons: a rat model study. Am J Rhinol Allergy 30:62–66. https://doi.org/10.2500/ajra.2016.30.4313
Koda T, Kuroda Y, Imai H (2009) Rutin supplementation in the diet has protective effects against toxicant-induced hippocampal injury by suppression of microglial activation and pro-inflammatory cytokines: protective effect of rutin against toxicant-induced hippocampal injury. Cell Mol Neurobiol 29:523–531. https://doi.org/10.1007/s10571-008-9344-4
Kohrle J (2015) Selenium and the thyroid. Curr Opin Endocrinol Diabetes Obes 22:392–401. https://doi.org/10.1097/MED.0000000000000190
Kosti et al (2015) Xanthine oxidase: isolation, assays of activity, and inhibition. J Chem 2015:8. https://doi.org/10.1155/2015/294858
Kudva AK, Shay AE, Prabhu KS (2015) Selenium and inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 309:G71–G77. https://doi.org/10.1152/ajpgi.00379.2014
Lawrence RA, Burk RF (2012) Glutathione peroxidase activity in selenium-deficient rat liver. 1976. Biochem Biophys Res Commun 425:503–509. https://doi.org/10.1016/j.bbrc.2012.08.016
Li SH, Yu ZX, Li CL, Nguyen HP, Zhou YX, Deng C, Li XJ (2003) Lack of huntingtin-associated protein-1 causes neuronal death resembling hypothalamic degeneration in Huntington's disease. J Neurosci 23:6956–6964
Lin SH, Chang HC, Chen PJ, Hsieh CL, Su KP, Sheen LY (2013) The antidepressant-like effect of ethanol extract of daylily flowers ( Jin Zhen Hua) in rats. J Tradit Complement Med 3:53–61. https://doi.org/10.4103/2225-4110.106548
Liu P, Li Y, Liu D, Ji X, Chi T, Li L, Zou L (2018) Tolfenamic acid attenuates 3-nitropropionic acid-induced biochemical alteration in mice. Neurochem Res 43:1938–1946. https://doi.org/10.1007/s11064-018-2615-7
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262S1046-2023(01)91262-9
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Ludolph AC, He F, Spencer PS, Hammerstad J, Sabri M (1991) 3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin. Can J Neurol Sci 18:492–498
Mahdy HM, Mohamed MR, Emam MA, Karim AM, Abdel-Naim AB, Khalifa AE (2014) The anti-apoptotic and anti-inflammatory properties of puerarin attenuate 3-nitropropionic-acid induced neurotoxicity in rats. Can J Physiol Pharmacol 92:252–258. https://doi.org/10.1139/cjpp-2013-0398
Martini LH, Jung F, Soares FA, Rotta LN, Vendite DA, Frizzo MES, Yunes RA, Calixto JB, Wofchuk S, Souza DO (2007) Naturally occurring compounds affect glutamatergic neurotransmission in rat brain. Neurochem Res 32:1950–1956. https://doi.org/10.1007/s11064-007-9393-y
Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175
Mohammadi S (2014) Effect of selenium on neurotoxicity in adult male mice exposed to formaldehyde. Electron Physician 6:939–943. https://doi.org/10.14661/2014.939-943
Nkpaa KW, Onyeso GI (2018) Rutin attenuates neurobehavioral deficits, oxidative stress, neuro-inflammation and apoptosis in fluoride treated rats. Neurosci Lett 682:92–99. https://doi.org/10.1016/j.neulet.2018.06.023
Oboh G, Adewuni TM, Ademiluyi AO, Olasehinde TA, Ademosun AO (2018) Phenolic constituents and inhibitory effects of Hibiscus sabdariffa L. (Sorrel) calyx on cholinergic, monoaminergic, and purinergic enzyme activities. J Diet Suppl 15:910–922. https://doi.org/10.1080/19390211.2017.1406426
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Ola MS, Ahmed MM, Ahmad R, Abuohashish HM, Al-Rejaie SS, Alhomida AS (2015) Neuroprotective effects of rutin in streptozotocin-induced diabetic rat retina. J Mol Neurosci 56:440–448. https://doi.org/10.1007/s12031-015-0561-2
Pagel P, Blome J, Wolf HU (2000) High-performance liquid chromatographic separation and measurement of various biogenic compounds possibly involved in the pathomechanism of Parkinson's disease. J Chromatogr B Biomed Sci Appl 746:297–304
Patel DK, Kumar R, Prasad SK, Sairam K, Hemalatha S (2011) Antidiabetic and in vitro antioxidant potential of Hybanthus enneaspermus (Linn) F. Muell in streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed 1:316–322. https://doi.org/10.1016/S2221-1691(11)60051-8
Pinto Brod LM, Fronza MG, Vargas JP, Ludtke DS, Luchese C, Wilhelm EA, Savegnago L (2016) Involvement of monoaminergic system in the antidepressant-like effect of (octylseleno)-xylofuranoside in the mouse tail suspension test. Prog Neuro-Psychopharmacol Biol Psychiatry 65:201–207. https://doi.org/10.1016/j.pnpbp.2015.10.008
Pravalika K, Sarmah D, Kaur H, Wanve M, Saraf J, Kalia K, Borah A, Yavagal DR, Dave KR, Bhattacharya P (2018) Myeloperoxidase and neurological disorder: a crosstalk. ACS Chem Neurosci 9:421–430. https://doi.org/10.1021/acschemneuro.7b00462
Pyrzanowska J, Piechal A, Blecharz-Klin K, Joniec-Maciejak I, Zobel A, Widy-Tyszkiewicz E (2012) Influence of long-term administration of rutin on spatial memory as well as the concentration of brain neurotransmitters in aged rats. Pharmacol Rep 64:808–816
Rajendran N, Subramaniam S, Lotha R, Pemaiah B, Sivasubramanian A (2016) Isolation and characterization of flavonoids and flavone glycosides from the ethnic traditional medicinal plant Cotoneaster bacillaris Wall. Ex Lindl Der Pharmacia Lettre 8:321–324
Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241. https://doi.org/10.1016/S0140-6736(00)02490-9
Richards G, Messer J, Waldvogel HJ, Gibbons HM, Dragunow M, Faull RL, Saura J (2011) Up-regulation of the isoenzymes MAO-A and MAO-B in the human basal ganglia and pons in Huntington's disease revealed by quantitative enzyme radioautography. Brain Res 1370:204–214. https://doi.org/10.1016/j.brainres.2010.11.020
Santamaria A et al (2005) Selenium reduces the proapoptotic signaling associated to NF-kappaB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum. Synapse 58:258–266. https://doi.org/10.1002/syn.20206
Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS (2002) Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem 306:79–82. https://doi.org/10.1006/abio.2002.5676S0003269702956769
Schwab LC, Garas SN, Drouin-Ouellet J, Mason SL, Stott SR, Barker RA (2015) Dopamine and Huntington’s disease. Expert Rev Neurother 15:445–458. https://doi.org/10.1586/14737175.2015.1025383
Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205. https://doi.org/10.1016/0003-2697(68)90092-4
Seeher S, Carlson BA, Miniard AC, Wirth EK, Mahdi Y, Hatfield DL, Driscoll DM, Schweizer U (2014) Impaired selenoprotein expression in brain triggers striatal neuronal loss leading to co-ordination defects in mice. Biochem J 462:67–75. https://doi.org/10.1042/BJ20140423
Shalaby HN, El-Tanbouly DM, Zaki HF (2018) Topiramate mitigates 3-nitropropionic acid-induced striatal neurotoxicity via modulation of AMPA receptors. Food Chem Toxicol 118:227–234. https://doi.org/10.1016/j.fct.2018.05.022
Sidhu A, Diwan V, Kaur H, Bhateja D, Singh CK, Sharma S, Padi SSV (2018) Nicotinamide reverses behavioral impairments and provides neuroprotection in 3-nitropropionic acid induced animal model ofHuntington's disease: implication of oxidative stress- poly(ADP- ribose) polymerase pathway. Metab Brain Dis 33:1911–1921. https://doi.org/10.1007/s11011-018-0297-0
Singh S, Jamwal S, Kumar P (2015) Piperine enhances the protective effect of curcumin against 3-NP induced neurotoxicity: possible neurotransmitters modulation mechanism. Neurochem Res 40:1758–1766. https://doi.org/10.1007/s11064-015-1658-2
Solovyev ND (2015) Importance of selenium and selenoprotein for brain function: from antioxidant protection to neuronal signalling. J Inorg Biochem 153:1–12. https://doi.org/10.1016/j.jinorgbio.2015.09.003
Suganya SN, Sumathi T (2017) Effect of rutin against a mitochondrial toxin, 3-nitropropionicacid induced biochemical, behavioral and histological alterations-a pilot study on Huntington's disease model in rats. Metab Brain Dis 32:471–481. https://doi.org/10.1007/s11011-016-9929-4
Thome GR et al (2018) Selenothymidine protects against biochemical and behavioral alterations induced by ICV-STZ model of dementia in mice. Chem Biol Interact 294:135–143. https://doi.org/10.1016/j.cbi.2018.08.004
Tunez I, Tasset I, Perez-De La Cruz V, Santamaria A (2010) 3-Nitropropionic acid as a tool to study the mechanisms involved in Huntington’s disease: past, present and future. Molecules 15:878–916. https://doi.org/10.3390/molecules15020878
Videnovic A (2013) Treatment of Huntington disease. Curr Treat Options Neurol 15:424–438. https://doi.org/10.1007/s11940-013-0219-8
Xie Y, Yang W, Chen X, Xiao J (2014) Inhibition of flavonoids on acetylcholine esterase: binding and structure-activity relationship. Food Funct 5:2582–2589. https://doi.org/10.1039/c4fo00287c
Zhang S, Qi Y, Xu Y, Han X, Peng J, Liu K, Sun CK (2013) Protective effect of flavonoid-rich extract from Rosa laevigata Michx on cerebral ischemia-reperfusion injury through suppression of apoptosis and inflammation. Neurochem Int 63:522–532. https://doi.org/10.1016/j.neuint.2013.08.008
Zolali E, Hamishehkar H, Maleki-Dizaji N, Majidi Zolbanin N, Ghavimi H, Kouhsoltani M, Asgharian P (2014) Selenium effect on oxidative stress factors in septic rats. Adv Pharm Bull 4:289–293. https://doi.org/10.5681/apb.2014.042
Zuccato C, Cattaneo E (2007) Role of brain-derived neurotrophic factor in Huntington's disease. Prog Neurobiol 81:294–330. https://doi.org/10.1016/j.pneurobio.2007.01.003
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Abdelfattah, M.S., Badr, S.E.A., Lotfy, S.A. et al. Rutin and Selenium Co-administration Reverse 3-Nitropropionic Acid-Induced Neurochemical and Molecular Impairments in a Mouse Model of Huntington’s Disease. Neurotox Res 37, 77–92 (2020). https://doi.org/10.1007/s12640-019-00086-y
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DOI: https://doi.org/10.1007/s12640-019-00086-y