The nigrostriatal pathway is a dopaminergic pathway that connects the substantia nigra with the dorsal striatum. Loss of dopamine neurons in the substantia nigra is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function in this pathway. This study aimed at evaluating the protective role of two anti-inflammatory drugs, indomethacin and nimesulide separately or in combination with vitamin C against biochemical disturbances, brain damage and motor impairment in rotenone-induced mice model of Parkinson's disease. Animals were divided into 7 groups. 1 st received the vehicle (DEMSO); 2nd received rotenone (1.5 mg/kg); 3rd received rotenone then were left for two weeks recovery; 4th rotenone + indomethacin (10 mg/kg); 5th received rotenone + indomethacin in combination with vitamin C (25 mg/kg). 6th received rotenone + nimesulide (10 mg/kg); group 7 received rotenone + nimesulide in combination with vitamin C. All treatments were given subcutaneously three times per week for one month. Rotenone treatment caused significant Increases in brain malondialdehyde (MDA), nitric oxide (NO), but induced significant decreases in brain reduced glutathione (GSH) level, acetylcholinesterase (AChE) activity, dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels. These changes lasted for two weeks after the termination of rotenone treatment. Histologically, Rotenone caused degeneration of neurons in striatum, cellular infiltration, atrophy, pyknosis, necrosis, as well as focal gliosis in cerebral cortex and pyknosis of pyramidal cells in the hippocampus. Furthermore, rotenone treatment caused a significant impairment in the motor function of the mice (stair test). Co-administration of indomethacin or nimesulide separately or in combination with vitamin C to rotenone treated mice resulted in alleviation of biochemical and motor activity but not the histological disturbances caused by rotenone treatment alone.
| Published in | European Journal of Clinical and Biomedical Sciences (Volume 3, Issue 4) |
| DOI | 10.11648/j.ejcbs.20170304.11 |
| Page(s) | 67-79 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Parkinson's Disease, Substantia Nigra, Striatum, Nigrostriatal, Rotenone, Indomethacin, Nimesulide
| [1] | Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T (Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies) Am. J. Pathol., 1998; 152, 879–884. |
| [2] | Cicchetti F, Drouin-Ouellet J, Gross RE (Environmental toxins and Parkinson's disease: what have we learned from pesticide-induced animal models) Trends Pharmacol Sci., 2009; 30, 475-483. |
| [3] | Marsden CD (Problems with long-term levodopa therapy for Parkinson's disease) Clin Neuropharmacol., 1994; 17, Suppl. 2, S32–S44. |
| [4] | Tedroff JM (Functional consequences of dopaminergic degeneration in Parkinson’s disease) Adv Neurol., 1999; 80: 67-70. |
| [5] | Bonnet A, Houeto J (Pathophysiology of Parkinson's disease) Biomed Pharmacotherapy, 1999; 53 (3), 117-121. |
| [6] | Sulzer D, Surmeier DJ (Neuronal vulnerability, pathogenesis and Parkinson’s disease) Mov Disord., 2013; 28, 715–724. |
| [7] | Politis M, Loane C (Serotonergic Dysfunction in Parkinson's Disease and Its Relevence to Disability) Scientific World Journal, 2011; 11, 1726-1734. |
| [8] | Halliday GM, Li YW, Blumbergs PC, Joh TH, Cotton RG, Howe PR, Blessing WW, Geffen LB (Neuropathology of immunohistochemically identified brainstem neurons in Parkinson’s disease) Ann Neurol., 1990; 27: 373–85. |
| [9] | Sherer TB, Betarbet R, Greenamyre JT (Environment, mitochondria, and Parkinson’s disease) Neuroscientist, 2002; 8: 192–197. |
| [10] | Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW (Rotenone, paraquat, and Parkinson’s disease) Environ Health Perspect., 2011; 119 (6), 866–872. |
| [11] | Wang A, Costello S, Cockburn M, Zhang X, Bronstein J, Ritz B (Parkinson’s disease risk from ambient exposure to pesticides) Eur J Epidemiol., 2011; 26(7): 547–555. |
| [12] | Lev N, Melamed E. (Heredity in Parkinson's disease: new findings) Isr Med Assoc J., 2001; 3, 435. |
| [13] | Di Monte DA, Lavasani M, Manning-Bog AB (Environmental factors in Parkinson’s disease) Neurotoxicology., 2002; 23(4–5):487–502. |
| [14] | Schapira AH (Mitochondria in the aetiology and pathogenesis of Parkinson’s disease) Lancet Neurol., 2008; 7:97–109. |
| [15] | Moldovan L, Moldovan NI (Oxygen free radicals and redox biology of organelles) Histochemistry and Cell Biology, 2004; vol. 122, no. 4, pp. 395–412. |
| [16] | Turrens JF (Superoxide production by the mitochondrial respiratory chain) Biosci Rep., 1997; 17(1), 3–8. |
| [17] | Facchinetti F, Dawson VL, Dawson TM (Free radicals as mediators of neuronal injury) Cell Mol Neurobiol., 1998; 18:667–682. |
| [18] | Halliwell B. (Free radicals and antioxidants – quo vadis) Trends Pharmacol Sci., 2011; 32, 125–130. |
| [19] | Moncada S. (Nitric oxide in the vasculature: physiology and pathophysiology) Ann N Y Acad Sci., 1997; 811:60-67. |
| [20] | Saran M, Michel C, Bors W. (Reaction of NO with Oº2-. Implications for the action of endothelium-derived relaxing factor (EDRF)) Free Radic Res Commun., 1990; 10:221-6. |
| [21] | Agil A, Duran R, Barrero F, Morales B, Arauzo M, Alba F (Plasma lipid peroxidation in sporadic Parkinson's disease. Role of the L-dopa) J Neurol Sci., 2006; 240, 31-36. |
| [22] | Alam Z, Daniel S, Lees A, Marsden D, Jenner P, Halliwell B (A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease) J Neurochem., 1997; 69, 1326-1329. |
| [23] | Dringen R (Metabolism and functions of glutathione in brain) Prog Neurobiol., 2000; 62:649–671. |
| [24] | Floor E, Wetzel MG (Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay) J Neurochem., 1998; 70:268–275. |
| [25] | Przedborski S, Jackson-Lewis V (ROS and Parkinson’s disease: a view to a kill. In Free Radicals in Brain Pathophysiology) G. Poli, E. Cadenas, and L. Packer, eds. New York: Marcel Dekker, niInc., 2000; pp. 273–290. |
| [26] | Sánchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell A, Isacson O (Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease) Journal of Neuroinflammation, 2004; 1:6. |
| [27] | Hirsch EC, Hunot S, Hartmann A. (Neuroinflammatory processes in Parkinson’s disease) Parkinsonism Relat Disord., 2005; 11 (Suppl 1): S9–S15. |
| [28] | Schulte T, Schols L, Muller T, Woitalla D, Berger K, Kruger R. (Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson’s disease) Neurosci Lett., 2002; 326:70–72. |
| [29] | Vane JR, Botting RM (Anti-inflammatory drugs and their mechanism of action) Inflamm Res., 1998; 47 (suppl 2): S78-S87. |
| [30] | O’Banion MK (Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology) Crit. Rev. Neurobiol., 1999; 13, 45–82. |
| [31] | Flower RJ (The development of COX2 inhibitors) Nat Rev Drug Discov., 2003; 2, 179–191. |
| [32] | Laurence L, Brunton J, John S, Keit L, editors (Non-dteroidal anti-inflammatory drugs) McGraw Hill. Goodman and Gill's. The pharmacological basis of therapeutics, 2006; pp. 673-706. |
| [33] | Vane JR (Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs) Nature (London), 1971; 231, 232–235. |
| [34] | Regula J, Butruk E, Dekkers CP, de Boer SY, Raps D, Simon L, Terjung A, Thomas KB, Luhmann R, Fischer R (Prevention of NSAID-associated gastrointestinal lesions: a comparison study pantoprazole versus omeprazole) Am. J. Gastroenterol., 2006; 101 (8), 1747–1755. |
| [35] | Chen H, Zhang SM, Hernán MA, Schwarzschild MA, Willett WC, Colditz GA, Speizer FE, Ascherio A (Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease) Arch Neurol., 2003; 60 (8): 1059-64. |
| [36] | Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A (Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease) Ann Neurol., 2005; 58: 963–967. |
| [37] | Herna´n MA, Logroscino G, García Rodríguez LA (Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease) Neurology, 2006; 66:1097–1099. |
| [38] | Manthripragada AD, Schernhammer ES, Qiu J, Friis S, Wermuth L, Olsen JH, Ritz B (Non-steroidal anti-inflammatory drug use and the risk of Parkinson's disease) Neuroepidemiology, 2011; 36 (3): 155-61. |
| [39] | Becker CJick SS Meier CR (NSAID use and risk of Parkinson disease: a population-based case-control study) Eur J Neurol., 2011; 18 (11): 1336-42. |
| [40] | Hardman JG, Limbird LE, Gilman AG. Goodman and Gilman’s (The Pharmacological Basic of Therapeutics) 10th International Edition, The McGraw-Hill Companies Inc., 2001. |
| [41] | Kurkowska-Jastrzebska I, Babiuch M, Joniec I, Przybylkowski A, Czlonkowski A, Czlonkowska A (Indomethacin protects against neurodegeneration caused by MPTP intoxication in mice) Int. Immunopharmacol., 2002; 2, 1213–1218. |
| [42] | Hawboldt J (Adverse events associated with NSAIDs) US Pharm., 2008; 33 (12): HS5-HS13. |
| [43] | Kataoka H, Horie Y, Koyama R, Nakatsugi S, Furukawa M (Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a preferential COX-2 inhibitor in the stomach) Dig Dis Sci., 2000; 45, 1366–1375. |
| [44] | Chandra J, Bhatnagar SK (Antipyretics in children) Indian J Pediatr., 2002; 69, 69–74. |
| [45] | Dhir A, Naidu PS, Kulkarni SK (Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice) Seizure, 2007; 16, 691. |
| [46] | Wang Y, Deng XL, Xiao XH, Yuan BX (A non-steroidal anti-inflammatory agent provides significant protection during focal ischemic stroke with decreased expression of matrix metalloproteinases) Curr Neurovasc Res., 2007; 4, 176. |
| [47] | Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov A, Greenamyre T (Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. nature neuroscience) volume 3 no 12, 2000. |
| [48] | He Y, Imam SZ, Dong Z, Jankovic J, Ali SF, Appel SH, Le W (Role of nitric oxide in rotenone-induced nigro-striatal injury) Journal of Neurochemistry, 2003; 86, 1338–1345. |
| [49] | Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H. (Antioxidant effects of estradiol and 2-hydroxyestradiol on iron induced lipid per¬oxidation of rat liver microsomes) Steroids, 1994; 59 (6): 383–388. |
| [50] | Ellman GL (Tissue sulfhydryl groups) Arch Biochem., 1959; 82 (1): 70–77. |
| [51] | Moshage H, Kok B, Huizenga JR, Jansen PL (Nitrite and nitrate deter¬mination in plasma: a critical evaluation) Clin Chem., 1995; 41 (6 Pt 1): 892–896. |
| [52] | Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (A new and rapid colorimetric determination of acetylcholinesterase activity) Biochem Pharmacol., 1961; 7: 88–95. |
| [53] | Gorun V, Proinov I, Baltescu V, Balaban G, Barzu O (Modified Ellman procedure for assay of cholinesterases in crude enzymatic preparation) Anal Biochem., 1978; 86 (1): 324–326. |
| [54] | Ciarlone AE (Further modification of a fluoremetric method for analyzing brain amines) Microchem. J., 1978; 23: 9-12. |
| [55] | Shore PA, Olin JS (Identification and chemical assay of norepinephrine in brain and other tissues) J Pharmacol EXP Ther., 1958; 122 (3): 295-300. |
| [56] | Baird AL, Meldrum A, Dunnett SB (The staircase test of skilled reaching in mice) Brain Res Bull., 2001; 54: 243–250. |
| [57] | Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT (Mechanism of toxicity in rotenone models of Parkinson’s disease) J Neurosci., 2003; 23: 10756-64. |
| [58] | Beal MF (Mitochondria and neurodegeneration) Novartis Found Symp., 2007; 287: 183–192. |
| [59] | Hensley K, Pye QN, Maidt ML, Stewart CA, Robinson KA, Floyd RA (Interaction of alpha-phenyl-N-tert-butyl nitrone and alternative electron acceptors with complex 1 indicates a substrate reduction site upstream from the rotenone binding site). J. Neurochem., 1998; 71, 2549–2557. |
| [60] | Verma R, Nehru B (Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson’s disease). Neurochem Int., 2009; 55 (6): 369–75. |
| [61] | Xiong N, Huang J, Zhang Z, Zhang Z, Xiong J (Stereotaxical Infusion of Rotenone: A Reliable Rodent Model for Parkinson's Disease) PLoSONE, 2009; 4 (11), e7878. |
| [62] | Chang CY, Song MJ, Jeon SB, Yoon HJ, Lee DK, Kim IH, Suk K, Choi DK, Park EJ ( Dual functionality of myeloper¬oxidase in rotenone-exposed brain-resident immune cells) Am J Pathol., 2011; 179 (2): 964–979. |
| [63] | Esterbauer H, Schaur JS, Zollner H. (Chemistry and biochemistry of 4- hydroxynonenal, malonaldehyde and related aldehydes) Free Radic Biol Med., 1991; 11: 81-128. |
| [64] | Gutteridge JM (Lipid peroxidation and antioxidants as biomarkers of tissue damage) Clin Chem., 1995; 41 (12 Pt 2): 1819–1828. |
| [65] | Murray, J., Taylor, S. W., Zhang, B., Ghosh, S. S., Capaldi, R. A. (2003). Oxidative damage to mitochondrial complex I due to peroxynitrite; Identification of reactive tyrosines by Mass spectrometry. J Biol Chem. 278 (39): 37223-30. |
| [66] | Vali S, Mythri R, Jagatha B, Padiadpu J, Ramanujan K, Andersen J. (Integrating glutathione metabolism and mitochondrial dysfunction with implications for Parkinson's Disease: a dynamic model) Neurosci., 2007; 149, 917-930. |
| [67] | Asanuma M, Miyazaki I. (Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson’s disease) Curr Pharm., 2008; 14: 1428 –1434. |
| [68] | Antony S, Gudluru S, Pal B, Vadivelan R, Kumar MN, Elango K, Suresh B (Indomethacin, nifedipine and its combination produced anti-Parkinson’s activity in 6-OHDA lesioned rat model) Pharmacie Globale (IJCP), 2010; 4 (05). |
| [69] | Asanuma M, Nishibayashi-Asanuma S, Miyazaki I, Kohno M, Ogawa N. (Neuroprotective effects of non-steroidal antiinflammatory drugs by direct scavenging of nitric oxide radicals) J Neurochem., 2001; 76: 1895-904. |
| [70] | Gupta A, Dhir A, Kumar A, Kulkarni SK (Effect of preferential cyclooxygenase-2 (COX-2) inhibitor against 1-methyl-4 phenyl-1, 2, 3-tertahydropyridine (MPTP)-induced striatal lesions in rats: Behavioral, biochemical and histological evidences) Indian Journal of Experimental Biology, 2010; 48, pp. 577-585. |
| [71] | Hoglinger G, Feger J, Prigent A, Michel P, Parain K, Champy P, Ruberg M, Oertel W, Hirsh E (Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats) J. Neurochem., 2003; 84, 491–502. |
| [72] | Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung, R, Jackson S, Gille G, Spillantini MG, Reichmann H, Funk R (Progression of Parkinson’s Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice) PLoS ONE. 2010; 5 (1): e8762. |
| [73] | Hirsch EC, Hunot S (Neuroinflammation in Parkinson's disease: A target for neuroprotection?) Lancet Neurol. 2009; 8, 382–397. |
| [74] | Lotharius J, Brundin P (Pathogenesis of Parkinson's disease: dopamine, vesicles and α-synuclein) Nat Rev Neurosci., 2002; 3 (12), 932-942. |
| [75] | Jana S, Maiti AK, Bagh MB, Banerjee K, Das A, Roy A, Chakrabarti S (Dopamine but not 3,4- dihydroxy phenylacetic acid (DOPAC) inhibits brain respiratory chain activity by autooxidation and mitochondria catalyzed oxidation to quinone products: implications in Parkinson’s disease) Brain Res., 2007; 1139: 195–200. |
| [76] | Gao HM, Hong JS, Zhang W, Liu B. (Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons) J. Neurosci., 2002; 22, 782–790. |
| [77] | LaVoie MJ, Hastings TG (Peroxynitrite- and nitrite-induced oxidation of dopamine: implications for nitric oxide in dopaminergic cell loss) J. Neurochem., 1999; 73, 2546–2554. |
| [78] | Imam SZ, Newport GD, Itzhak Y, Cadet JL, Islam F, Slikker W, Ali SFJr (Peroxynitrite plays a role in methamphetamine-induced dopaminergic neurotoxicity: evidence from mice lacking neuronal nitric oxide synthase gene or overexpressing copper-zinc superoxide dismutase) J. Neurochem., 2001; 76, 745–749. |
| [79] | Minghetti L (2004). (Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases) J. Neuropathol. Exp. Neurol., 2004; 63, 901-910. |
| [80] | Abdel-Rahman M, Ahmed HH, Moniem AE (Ameliorative effect of grape seed extract against rotenone-induced neurotoxicity in adult male albino rats) JASMR, 2008; 3 (2), 227-242. |
| [81] | Jellinger K. (New developments in the pathology of Parkinson's disease) Adv Neurol., 1990; 53: 1–16. |
| [82] | Zgaljardic DJ, Foldi NS, Borod JC (Cognitive and behavioral dysfunction in Parkinson’s disease: neurochemical and clinicopathological contributions) J Neural Transm., 2004; 111:1287–1301. |
| [83] | Zhang X, Lu L, Liu S, Ye W, Wu J. (Acetylcholinesterase deficiency decreases apoptosis in dopaminergic neurons in the neurotoxin model of Parkinson's disease. International Journal of Biochemistry) 2013; Vol. 45 Issue 2, p265-272. 8p. |
| [84] | Shimada H, Hirano S, Shinotoh H, Aotsuka A, Sato K, Tanaka N, Ota T, Asahina M, Fukushi K, Kuwabara S, Hattori T, Suhara T, Irie T (Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET) Neurology, 2009; 73: 273–8. |
| [85] | Zarow C, Lyness SA, Mortimer JA, Chui HC (Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases) Arch Neurol., 2003; 60: 337–41. |
| [86] | Selden NR, Gitelman DR, Salamon-Murayama N, Parrish TB, Mesulam MM (Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain) Brain, 1998; 121: 2249–57. |
| [87] | Sergei A, David A, Mei Q, Mark V. (Human Keratinocytes Synthesize, Secrete, and Degrade Acetylcholine) J Invest Dermatol., 1993; 101: 32-36. |
| [88] | McKinney M, Coyle JT (The potential for muscarinic receptor subtype-specefic pharmacotherapy for Alzheimer's disease) Mayo Clin Proc., 1991; 66: 1225-1237. |
| [89] | Jakeman P, Maxwell S. (Effects of antioxidant vitamin supplementation on muscle function after eccentric exercise) Eur J Appl Physiol., 1993; 67: 426-30. |
| [90] | Makar TK, Nedergaard M, Preuss A, Gelbard AS, Perumal AS and Cooper AJ (Vitamin E, ascorbate, glutathione, glutathione disulfide, and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: evidence that astrocytes play an important role in antioxidative processes in the brain) Journal of Neurochemistry, 1994; 62: 45-53. |
| [91] | Wagner GC, Carelli RM, Jarvis MF (Ascorbic acid reduces the dopamine depletion induced by methamphetamine and the l-methyl-4-phenylpyridinium ion) Neuropharmacology, 1986; 25: 559-561. |
| [92] | Nehru B, Verma R, Khanna P, Sharma SK (Behavioral alterations in rotenone model of Parkinson’s disease: attenuation by co-treatment of centrophenoxine) Brain Res., 2008; 1201: 122–7. |
| [93] | Weiner D, Levey A, Brann M. (Expression of muscarian acetylcholine and dopamine receptor mRNAs in rat basal ganglia) Proc. Nati. Acad. Sci. USA., 1990; Vol. 87, pp. 7050-7054. |
| [94] | Zhu W, Wang D, Zheng J, An Y, Wang Q, Zhang W, Jin L, Gao H, Lin L. (Effect of (R)-Salsolinol and N-Methyl-(R)-Salsolinol on the Balance Impairment between Dopamine and Acetylcholine in Rat Brain: Involvement in Pathogenesis of Parkinson Disease) Clinical Chemistry, 2008; 54:4; 705–712. |
APA Style
Nagi Ali Ibrahim, Omar Mohamed Abdel-Salam, Yasser Ashry Khadrawy, Amal Mohamed Hashem, Eman Mohamed Sameer. (2017). Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice. European Journal of Clinical and Biomedical Sciences, 3(4), 67-79. https://doi.org/10.11648/j.ejcbs.20170304.11
ACS Style
Nagi Ali Ibrahim; Omar Mohamed Abdel-Salam; Yasser Ashry Khadrawy; Amal Mohamed Hashem; Eman Mohamed Sameer. Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice. Eur. J. Clin. Biomed. Sci. 2017, 3(4), 67-79. doi: 10.11648/j.ejcbs.20170304.11
AMA Style
Nagi Ali Ibrahim, Omar Mohamed Abdel-Salam, Yasser Ashry Khadrawy, Amal Mohamed Hashem, Eman Mohamed Sameer. Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice. Eur J Clin Biomed Sci. 2017;3(4):67-79. doi: 10.11648/j.ejcbs.20170304.11
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author = {Nagi Ali Ibrahim and Omar Mohamed Abdel-Salam and Yasser Ashry Khadrawy and Amal Mohamed Hashem and Eman Mohamed Sameer},
title = {Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice},
journal = {European Journal of Clinical and Biomedical Sciences},
volume = {3},
number = {4},
pages = {67-79},
doi = {10.11648/j.ejcbs.20170304.11},
url = {https://doi.org/10.11648/j.ejcbs.20170304.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ejcbs.20170304.11},
abstract = {The nigrostriatal pathway is a dopaminergic pathway that connects the substantia nigra with the dorsal striatum. Loss of dopamine neurons in the substantia nigra is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function in this pathway. This study aimed at evaluating the protective role of two anti-inflammatory drugs, indomethacin and nimesulide separately or in combination with vitamin C against biochemical disturbances, brain damage and motor impairment in rotenone-induced mice model of Parkinson's disease. Animals were divided into 7 groups. 1 st received the vehicle (DEMSO); 2nd received rotenone (1.5 mg/kg); 3rd received rotenone then were left for two weeks recovery; 4th rotenone + indomethacin (10 mg/kg); 5th received rotenone + indomethacin in combination with vitamin C (25 mg/kg). 6th received rotenone + nimesulide (10 mg/kg); group 7 received rotenone + nimesulide in combination with vitamin C. All treatments were given subcutaneously three times per week for one month. Rotenone treatment caused significant Increases in brain malondialdehyde (MDA), nitric oxide (NO), but induced significant decreases in brain reduced glutathione (GSH) level, acetylcholinesterase (AChE) activity, dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels. These changes lasted for two weeks after the termination of rotenone treatment. Histologically, Rotenone caused degeneration of neurons in striatum, cellular infiltration, atrophy, pyknosis, necrosis, as well as focal gliosis in cerebral cortex and pyknosis of pyramidal cells in the hippocampus. Furthermore, rotenone treatment caused a significant impairment in the motor function of the mice (stair test). Co-administration of indomethacin or nimesulide separately or in combination with vitamin C to rotenone treated mice resulted in alleviation of biochemical and motor activity but not the histological disturbances caused by rotenone treatment alone.},
year = {2017}
}
TY - JOUR T1 - Non-Steroidal Anti-Inflammatory Drugs and Vitamin C in the Rotenone Induced Nigrostriatal Damage in Mice AU - Nagi Ali Ibrahim AU - Omar Mohamed Abdel-Salam AU - Yasser Ashry Khadrawy AU - Amal Mohamed Hashem AU - Eman Mohamed Sameer Y1 - 2017/07/04 PY - 2017 N1 - https://doi.org/10.11648/j.ejcbs.20170304.11 DO - 10.11648/j.ejcbs.20170304.11 T2 - European Journal of Clinical and Biomedical Sciences JF - European Journal of Clinical and Biomedical Sciences JO - European Journal of Clinical and Biomedical Sciences SP - 67 EP - 79 PB - Science Publishing Group SN - 2575-5005 UR - https://doi.org/10.11648/j.ejcbs.20170304.11 AB - The nigrostriatal pathway is a dopaminergic pathway that connects the substantia nigra with the dorsal striatum. Loss of dopamine neurons in the substantia nigra is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function in this pathway. This study aimed at evaluating the protective role of two anti-inflammatory drugs, indomethacin and nimesulide separately or in combination with vitamin C against biochemical disturbances, brain damage and motor impairment in rotenone-induced mice model of Parkinson's disease. Animals were divided into 7 groups. 1 st received the vehicle (DEMSO); 2nd received rotenone (1.5 mg/kg); 3rd received rotenone then were left for two weeks recovery; 4th rotenone + indomethacin (10 mg/kg); 5th received rotenone + indomethacin in combination with vitamin C (25 mg/kg). 6th received rotenone + nimesulide (10 mg/kg); group 7 received rotenone + nimesulide in combination with vitamin C. All treatments were given subcutaneously three times per week for one month. Rotenone treatment caused significant Increases in brain malondialdehyde (MDA), nitric oxide (NO), but induced significant decreases in brain reduced glutathione (GSH) level, acetylcholinesterase (AChE) activity, dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels. These changes lasted for two weeks after the termination of rotenone treatment. Histologically, Rotenone caused degeneration of neurons in striatum, cellular infiltration, atrophy, pyknosis, necrosis, as well as focal gliosis in cerebral cortex and pyknosis of pyramidal cells in the hippocampus. Furthermore, rotenone treatment caused a significant impairment in the motor function of the mice (stair test). Co-administration of indomethacin or nimesulide separately or in combination with vitamin C to rotenone treated mice resulted in alleviation of biochemical and motor activity but not the histological disturbances caused by rotenone treatment alone. VL - 3 IS - 4 ER -
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