Generic placeholder image

Current Aging Science

Editor-in-Chief

ISSN (Print): 1874-6098
ISSN (Online): 1874-6128

Research Article

Parkinsonism-like Disease Induced by Rotenone in Rats: Treatment Role of Curcumin, Dopamine Agonist and Adenosine A2A Receptor Antagonist

Author(s): Asmaa Fathy Aboul Naser, Wessam Magdi Aziz, Yomna Rashad Ahmed, Wagdy Khalil Bassaly Khalil and Manal Abdel Aziz Hamed *

Volume 15, Issue 1, 2022

Published on: 26 May, 2021

Page: [65 - 76] Pages: 12

DOI: 10.2174/1874609814666210526115740

Price: $65

conference banner
Abstract

Background: Parkinsonism is a neurodegenerative disorder that affects elderly people worldwide.

Methods: Curcumin, adenosine A2AR antagonist (ZM241385) and Sinemet® (L-dopa) were evaluated against Parkinson’s disease (PD) induced by rotenone in rats, and the findings were compared to our previous study on mice model.

Results: Rats injected with rotenone showed severe alterations in adenosine A2A receptor gene expression, oxidative stress markers, inflammatory mediator, energetic indices, apoptotic marker and DNA fragmentation levels as compared to the control group. Treatments with curcumin, ZM241385, and Sinemet® restored all the selected parameters. The brain histopathological features of cerebellum regions confirmed our results. By comparing our results with the previous results on mice, we noticed that mice respond to rotenone toxicity and treatments more than rats with regards to behavioral observation, A2AR gene expression, neurotransmitter levels, inflammatory mediator and apoptotic markers, while rats showed higher response to treatments regarding oxidative stress and energetic indices.

Conclusion: Curcumin succeeded in attenuating the severe effects of Parkinson’s disease in the rat model and can be considered as a potential dietary supplement. Adenosine A2AR antagonist has almost the same pattern of improvement as Sinemet® and may be considered as a promising therapy against PD. To compare the role of animal species in response to PD symptoms and treatments, our previous report on mice explored the response of mice to rotenone toxicity in comparison with rats, where rats have shown a higher response to treatments. Therefore, no animal model can perfectly recapitulate all the pathologies of PD.

Keywords: Curcumin, rotenone, rats, parkinsonism, A2AR antagonist, histopathological features.

Graphical Abstract

[1]
Imai Y, Venderova K, Park DS, Cai H, Schmidt E. Animal models of Parkinson’s disease. Parkinsons Dis 2011; 2011364328
[http://dx.doi.org/10.4061/2011/364328] [PMID: 22220287]
[2]
Zeng XS, Geng WS, Jia JJ. Neurotoxin-induced animal models of Parkinson disease: Pathogenic mechanism and assessment. ASN Neuro 2018; 101759091418777438
[http://dx.doi.org/10.1177/1759091418777438] [PMID: 29809058]
[3]
Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nat Rev Neurosci 2017; 18(7): 435-50.
[http://dx.doi.org/10.1038/nrn.2017.62] [PMID: 28592904]
[4]
Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000; 3(12): 1301-6.
[http://dx.doi.org/10.1038/81834] [PMID: 11100151]
[5]
Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24(2): 197-211.
[http://dx.doi.org/10.1016/S0197-4580(02)00065-9] [PMID: 12498954]
[6]
Shahmoradian SH, Lewis AJ, Genoud C, et al. Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes. Nat Neurosci 2019; 22(7): 1099-109.
[http://dx.doi.org/10.1038/s41593-019-0423-2] [PMID: 31235907]
[7]
Terron A, Bal-Price A, Paini A, et al. An adverse outcome pathway for parkinsonian motor deficits associated with mitochondrial complex I inhibition. Arch Toxicol 2018; 92(1): 41-82.
[http://dx.doi.org/10.1007/s00204-017-2133-4] [PMID: 29209747]
[8]
Worth AJ, Basu SS, Snyder NW, Mesaros C, Blair IA. Inhibition of neuronal cell mitochondrial complex I with rotenone increases lipid β-oxidation, supporting acetyl-coenzyme A levels. J Biol Chem 2014; 289(39): 26895-903.
[http://dx.doi.org/10.1074/jbc.M114.591354] [PMID: 25122772]
[9]
Lapointe N, St-Hilaire M, Martinoli MG, et al. Rotenone induces non-specific central nervous system and systemic toxicity. FASEB J 2004; 18(6): 717-9.
[http://dx.doi.org/10.1096/fj.03-0677fje] [PMID: 14766796]
[10]
Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT. Rotenone induces non-specific central nervous system and systemic toxicity. Neurobiol Dis 2009; 34: 279-90.
[http://dx.doi.org/10.1016/j.nbd.2009.01.016] [PMID: 19385059]
[11]
Johnson ME, Bobrovskaya L. An update on the rotenone models of Parkinson’s disease: Their ability to reproduce the features of clinical disease and model gene-environment interactions. Neurotoxicology 2015; 46: 101-16.
[http://dx.doi.org/10.1016/j.neuro.2014.12.002] [PMID: 25514659]
[12]
Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 2004; 44(2): 97-111.
[http://dx.doi.org/10.1080/10408690490424702] [PMID: 15116757]
[13]
Deng SL, Chen WF, Yang BZL, Liu ZL. Protective effects of curcumin and its analogues against free radical-induced oxidative haemolysis of human red blood cells. Food Chem 2006; 98: 112-9.
[http://dx.doi.org/10.1016/j.foodchem.2005.05.063]
[14]
Baliga MS, Katiyar SK. Chemoprevention of photocarcinogenesis by selected dietary botanicals. Photochem Photobiol Sci 2006; 5(2): 243-53.
[http://dx.doi.org/10.1039/B505311K] [PMID: 16465310]
[15]
Suryanarayana P, Krishnaswamy K, Reddy GB. Effect of curcumin on galactose-induced cataractogenesis in rats. Mol Vis 2003; 9: 223-30.
[PMID: 12802258]
[16]
Mukhopadhyay A, Basu N, Ghatak N, Gujral PK. Anti-inflammatory and irritant activities of curcumin analogues in rats. Agents Actions 1982; 12(4): 508-15.
[http://dx.doi.org/10.1007/BF01965935] [PMID: 7180736]
[17]
Arafa HM. Curcumin attenuates diet-induced hypercholesterolemia in rats. Med Sci Monit 2005; 11(7): BR228-34.
[PMID: 15990684]
[18]
Kuroda M, Mimaki Y, Nishiyama T, et al. Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice. Biol Pharm Bull 2005; 28(5): 937-9.
[http://dx.doi.org/10.1248/bpb.28.937] [PMID: 15863912]
[19]
Jain SK, Rains J, Jones K. Effect of curcumin on protein glycosylation, lipid peroxidation, and oxygen radical generation in human red blood cells exposed to high glucose levels. Free Radic Biol Med 2006; 41(1): 92-6.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.03.008] [PMID: 16781457]
[20]
Zheng Z, Poon WS. Rodent model of Parkinson’s disease: Unilateral or bilateral? Alzheimers dis Parkinsonism 2017; 7: 1-5
[21]
Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M. Targeting adenosine A2A receptors in Parkinson’s disease. Trends Neurosci 2006; 29(11): 647-54.
[http://dx.doi.org/10.1016/j.tins.2006.09.004] [PMID: 17030429]
[22]
Morelli M, Di Paolo T, Wardas J, Calon F, Xiao D, Schwarzschild MA. Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. Prog Neurobiol 2007; 83(5): 293-309.
[http://dx.doi.org/10.1016/j.pneurobio.2007.07.001] [PMID: 17826884]
[23]
Hamed MA, Naser AFA, Aziz WM, et al. Natural sources, dopaminergic and non-dopaminergic agents for therapeutic assessment of Parkinsonism in rat model. PharmaNutrition 2020; •••100171
[http://dx.doi.org/10.1016/j.phanu.2019.100171]
[24]
Hamed MA, Mohammed MA, Naser AFA, et al. Optimization of curcuminoids extraction for evaluation against Parkinson’s disease in rats. J Biol Act Prod Nat 2019; 9: 335-51.
[http://dx.doi.org/10.1080/22311866.2019.1698317]
[25]
Xu K, Bastia E, Schwarzschild M. Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson’s disease. Pharmacol Ther 2005; 105(3): 267-310.
[http://dx.doi.org/10.1016/j.pharmthera.2004.10.007] [PMID: 15737407]
[26]
Ochi M, Koga K, Kurokawa M, Kase H, Nakamura J, Kuwana Y. Systemic administration of adenosine A(2A) receptor antagonist reverses increased GABA release in the globus pallidus of unilateral 6-hydroxydopamine-lesioned rats: A microdialysis study. Neuroscience 2000; 100(1): 53-62.
[http://dx.doi.org/10.1016/S0306-4522(00)00250-5] [PMID: 10996458]
[27]
Tozzi A, Tscherter A, Belcastro V, et al. Interaction of A2A adenosine and D2 dopamine receptors modulates corticostriatal glutamatergic transmission. Neuropharmacology 2007; 53(6): 783-9.
[http://dx.doi.org/10.1016/j.neuropharm.2007.08.006] [PMID: 17889039]
[28]
El Shebiney SA, El-Denshary ES, Abdel-Salam OME, et al. Cannabis resin extract in Parkinson’s disease: Behavioral, neurochemical, and histological evaluation Cell Biol. Respir Ther 2014; 3: 1-11.
[29]
Rajeswari A, Sabesan M. Inhibition of monoamine oxidase-B by the polyphenolic compound, curcumin and its metabolite tetrahydrocurcumin, in a model of Parkinson’s disease induced by MPTP neurodegeneration in mice. Inflammopharmacology 2008; 16(2): 96-9.
[http://dx.doi.org/10.1007/s10787-007-1614-0] [PMID: 18408903]
[30]
Fathalla AM, Soliman AM, Ali MH, Moustafa AA. Adenosine A2A receptor blockade prevents rotenone-induced motor impairment in a rat model of Parkinsonism. Front Behav Neurosci 2016; 10: 35.
[http://dx.doi.org/10.3389/fnbeh.2016.00035] [PMID: 26973484]
[31]
Alam M, Schmidt WJ. L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats. Behav Brain Res 2004; 153(2): 439-46.
[http://dx.doi.org/10.1016/j.bbr.2003.12.021] [PMID: 15265640]
[32]
Sanberg P, Martinez R, Shytle R, Cahill D. The catalepsy test: is a standardized method possible?Motor Activity and Movement Disorders. NY, USA: Humana Press 1996.
[http://dx.doi.org/10.1007/978-1-59259-469-6_7]
[33]
Khalil WKB, Booles HF. Protective role of selenium against over-expression of cancer-related apoptotic genes induced by o-cresol in rats. Arh Hig Rada Toksikol 2011; 62(2): 121-9.
[http://dx.doi.org/10.2478/10004-1254-62-2011-2074] [PMID: 21705299]
[34]
Linjawi SAA, Khalil WKB, Salem LM. Detoxified Jatropha curcaskernel meal impact against benzene- induced genetic toxicity in male rats. Int J Pharm 2014; 4: 57-66.
[35]
Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979; 582(1): 67-78.
[http://dx.doi.org/10.1016/0304-4165(79)90289-7] [PMID: 760819]
[36]
Wills ED. Mechanisms of lipid peroxide formation in animal tissues. Biochem J 1966; 99(3): 667-76.
[http://dx.doi.org/10.1042/bj0990667] [PMID: 5964963]
[37]
Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 1978; 186(1): 189-95.
[http://dx.doi.org/10.1016/0003-9861(78)90479-4] [PMID: 24422]
[38]
Montgomery HAC, Dymock JF. The determination of nitrite in water. Analyst (Lond) 1961; 86: 414-6.
[39]
Zagrodzka J, Romaniuk A, Wieczorek M, Boguszewski P. Bicuculline administration into ventromedial hypothalamus: effects on fear and regional brain monoamines and GABA concentrations in rats. Acta Neurobiol Exp (Warsz) 2000; 60(3): 333-43.
[PMID: 11016075]
[40]
Sun X, Wang D, Yu H, Hu L. Serial cytokine levels during wound healing in rabbit maxillary sinus mucosa. Acta Otolaryngol 2010; 130(5): 607-13.
[http://dx.doi.org/10.3109/00016480903352975] [PMID: 19958244]
[41]
Pradeep AR, Suke DK, Prasad MV, et al. Expression of key executioner of apoptosis caspase-3 in periodontal health and disease. J Investig Clin Dent 2016; 7(2): 174-9.
[http://dx.doi.org/10.1111/jicd.12134] [PMID: 25388853]
[42]
Lu T, Xu Y, Mericle MT, Mellgren RL. Participation of the conventional calpains in apoptosis. Biochim Biophys Acta 2002; 1590(1-3): 16-26.
[http://dx.doi.org/10.1016/S0167-4889(02)00193-3] [PMID: 12063165]
[43]
Rice ME, Shelton E. Comparison of the reduction of two tetrazolium salts with succinoxidase activity of tissue homogenates. J Natl Cancer Inst 1957; 18(1): 117-25.
[PMID: 13398820]
[44]
Babson AL, Babson SR. Kinetic colorimetric measurement of serum lactate dehydrogenase activity. Clin Chem 1973; 19(7): 766-9.
[http://dx.doi.org/10.1093/clinchem/19.7.766] [PMID: 4351362]
[45]
Bancroft J, Stevens A. Theory and practice of histological techniques. 4th ed. London: Churchill Livingstone 1996; pp. 40-138.
[46]
Khuwaja G, Khan MM, Ishrat T, et al. Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: Behavioral, neurochemical and immunohistochemical studies. Brain Res 2011; 1368: 254-63.
[47]
Muthian G, Mackey V, Prasad K, Charlton CJ. Curcumin and an antioxidant formulation protect C57BL/6J mice from MPTP-induced Parkinson’s disease like changes: potential neuroprotection for neurodegeneration. Parkinsonism Restless Legs Synd 2018; 8: 49-59.
[http://dx.doi.org/10.2147/JPRLS.S151452]
[48]
Motawi TK, Sadik NAH, Hamed MA, Ali SA, Khalil WKB, Ahmed YR. Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson’s disease mice model. Mol Cell Biochem 2020; 465(1-2): 89-102.
[http://dx.doi.org/10.1007/s11010-019-03670-0] [PMID: 31820278]
[49]
Jin F, Wu Q, Lu YF, Gong QH, Shi JS. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur J Pharmacol 2008; 600(1-3): 78-82.
[http://dx.doi.org/10.1016/j.ejphar.2008.10.005] [PMID: 18940189]
[50]
Schulz JB, Lindenau J, Seyfried J, Dichgans J. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 2000; 267(16): 4904-11.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01595.x] [PMID: 10931172]
[51]
Magalingam KB, Radhakrishnan A, Haleagrahara N. Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells. Int J Immunopathol Pharmacol 2016; 29(1): 30-9.
[http://dx.doi.org/10.1177/0394632015613039] [PMID: 26542606]
[52]
Džoljić E, Grabatinić I, Kostić V. Why is nitric oxide important for our brain? Funct Neurol 2015; 30: 159-63.
[53]
Cui Q, Li X, Zhu H. Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol Med Rep 2016; 13(2): 1381-8.
[http://dx.doi.org/10.3892/mmr.2015.4657] [PMID: 26648392]
[54]
Kish SJ, Tong J, Hornykiewicz O, et al. Preferential loss of serotonin markers in caudate versus putamen in Parkinson’s disease. Brain 2008; 131(Pt 1): 120-31.
[PMID: 17956909]
[55]
Politis M, Loane C. Serotonergic dysfunction in Parkinson’s disease and its relevance to disability. ScientificWorldJournal 2011; 11: 1726-34.
[http://dx.doi.org/10.1100/2011/172893] [PMID: 22125431]
[56]
Espay AJ, LeWitt PA, Kaufmann H. Norepinephrine deficiency in Parkinson’s disease: The case for noradrenergic enhancement. Mov Disord 2014; 29(14): 1710-9.
[http://dx.doi.org/10.1002/mds.26048] [PMID: 25297066]
[57]
Xu Y, Ku B, Cui L, et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 2007; 1162: 9-18.
[http://dx.doi.org/10.1016/j.brainres.2007.05.071] [PMID: 17617388]
[58]
Martin LJ. DNA damage and repair: relevance to mechanisms of neurodegeneration. J Neuropathol Exp Neurol 2008; 67(5): 377-87.
[http://dx.doi.org/10.1097/NEN.0b013e31816ff780] [PMID: 18431258]
[59]
Yuan J, Ren J, Wang Y, He X, Zhao Y. Acteoside binds to caspase-3 and exerts neuroprotection in the rotenone rat model of Parkinson’s disease. PLoS One 2016; 11(9)e0162696
[http://dx.doi.org/10.1371/journal.pone.0162696] [PMID: 27632381]
[60]
Chen G, Liu J, Jiang L, et al. Galangin reduces the loss of dopaminergic neurons in an LPS-evoked model of Parkinson’s disease in rats. Int J Mol Sci 2017; 19(1): 1-13.
[PMID: 29267220]
[61]
Hartmann A, Hunot S, Michel PP, et al. Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson’s disease. Proc Natl Acad Sci USA 2000; 97(6): 2875-80.
[http://dx.doi.org/10.1073/pnas.040556597] [PMID: 10688892]
[62]
Chen J, Nagayama T, Jin K, et al. Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. J Neurosci 1998; 18(13): 4914-28.
[http://dx.doi.org/10.1523/JNEUROSCI.18-13-04914.1998] [PMID: 9634557]
[63]
Hegde ML, Hegde PM, Holthauzen LM, Hazra TK, Rao KS, Mitra S. Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: Potential etiological linkage to neurodegenerative diseases. J Biol Chem 2010; 285(37): 28812-25.
[http://dx.doi.org/10.1074/jbc.M110.126664] [PMID: 20622253]
[64]
Farshbaf MJ. Succinate dehydrogenase in Parkinson’s disease. Front Biol 2017; 12: 175-82.
[http://dx.doi.org/10.1007/s11515-017-1450-6]
[65]
Powers R, Lei S, Anandhan A, et al. Metabolic investigations of the molecular mechanisms associated with Parkinson’s disease. Metabolites 2017; 7(2): 22.
[http://dx.doi.org/10.3390/metabo7020022] [PMID: 28538683]
[66]
Jha N, Jurma O, Lalli G, et al. Glutathione depletion in PC12 results in selective inhibition of mitochondrial dihydoxyvitamin D3- and ATRA-induced differentiation of humanpromyelocytic leukemia HL-60 cells. Eur J Pharmacol 2000; 420: 83-90.
[67]
Ross JM, Öberg J, Brené S, et al. High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio. Proc Natl Acad Sci USA 2010; 107(46): 20087-92.
[http://dx.doi.org/10.1073/pnas.1008189107] [PMID: 21041631]
[68]
Cook C, Stetler C, Petrucelli L. Disruption of protein quality control in Parkinson’s disease. Cold Spring Harb Perspect Med 2012; 2(5)a009423
[http://dx.doi.org/10.1101/cshperspect.a009423] [PMID: 22553500]
[69]
Khadrawy YA, Salem AM, El-Shamy KA, Ahmed EK, Fadl NN, Hosny EN. Neuroprotective and therapeutic effect of caffeine on the rat model of Parkinson’s disease induced by rotenone. J Diet Suppl 2017; 14(5): 553-72.
[http://dx.doi.org/10.1080/19390211.2016.1275916] [PMID: 28301304]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy