Skip to main content
SpringerLink
Log in

Sitagliptin and Liraglutide Modulate L-dopa Effect and Attenuate Dyskinetic Movements in Rotenone-Lesioned Rats

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

L-dopa is still considered as the gold standard therapy for Parkinson’s disease (PD); however, L-dopa-induced dyskinesia (LID) is a serious complication of long-term L-dopa treatment. The present study investigated the therapeutic potential of sitagliptin and liraglutide in comparisons with L-dopa against PD. In addition, their capacity to modulate L-dopa dose and/or side effects was investigated, too. Rats were injected with rotenone (3 mg/kg/day, s.c.) for 10 consecutive days to induce the experimental PD. The rotenone-treated rats were administered sitagliptin (30 mg/kg/day, p.o.) and liraglutide (50 μg/kg, s.c.) for 16 days either alone or together with L-dopa/carbidopa (50/25 mg/kg/day, i.p.). Scoring of LID was done on days 2, 4, 8, 12, and 16 in all L-dopa-treated groups. Twenty-four hours after the last administered dose of tested drugs, the behavior of rats in each group was screened by using the open-field test. Sitagliptin and liraglutide revealed marked attenuation of LID scores; in addition, they markedly increased animals’ motor performance. Moreover, they preserved substantia nigra pars compacta (SNpc) tyrosine hydroxylase (TH) and vesicular monoamine transporter 2–positive (VMAT2) cells with prominent increase of the striatal dopamine (DA) content. On the other hand, they significantly decreased nigral neuromelanin (NM)–positive cells, activated microglia, gliosis, and other pathological changes. In conclusion, sitagliptin and liraglutide could be a promising therapeutic challenger in PD, modifying L-dopa effect and/or allowing the use of L-dopa with fewer side effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

AIMs:

Abnormal involuntary movements

CNS:

Central nervous system

DA:

Dopamine

GLP-1R:

Glucagon-like peptide-1 receptor

GPCR:

G protein-coupled receptor

LID:

L-dopa-induced dyskinesia

NM:

Neuromelanin

PD:

Parkinson’s disease

SNpc:

Substantia nigra pars compacta

TH:

Tyrosine hydroxylase

VMAT2:

Vesicular monoamine transporter 2

References

  • Abdelsalam RM, Safar MM (2015) Neuroprotective effects of vildagliptin in rat rotenone Parkinson’s disease model: role of RAGE-NFkappaB and Nrf2-antioxidant signaling pathways. J Neurochem 133:700–707

    Article  PubMed  CAS  Google Scholar 

  • Abdin AA, Sarhan NI (2011) Intervention of mitochondrial dysfunction-oxidative stress-dependent apoptosis as a possible neuroprotective mechanism of alpha-lipoic acid against rotenone-induced Parkinsonism and L-dopa toxicity. Neurosci Res 71:387–395

    Article  PubMed  CAS  Google Scholar 

  • Abuirmeileh A, Harkavyi A, Rampersaud N, Lever R, Tadross JA, Bloom SR, Whitton PS (2012) Exendin-4 treatment enhances L-DOPA evoked release of striatal dopamine and decreases dyskinetic movements in the 6-hydoxydopamine lesioned rat. J Pharm Pharmacol 64:637–643

    Article  PubMed  CAS  Google Scholar 

  • Alam M, Schmidt WJ (2002) Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 136:317–324

    Article  PubMed  CAS  Google Scholar 

  • Alam M, Mayerhofer A, Schmidt WJ (2004) The neurobehavioral changes induced by bilateral rotenone lesion in medial forebrain bundle of rats are reversed by L-DOPA. Behav Brain Res 151:117–124

    Article  PubMed  CAS  Google Scholar 

  • Alves G, Forsaa EB, Pedersen KF, Dreetz Gjerstad M, Larsen JP (2008) Epidemiology of Parkinson’s disease. J Neurol 255(Suppl 5):18–32

    Article  PubMed  Google Scholar 

  • Athauda D, Foltynie T (2016) The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action. Drug Discov Today 21:802–818

    Article  PubMed  CAS  Google Scholar 

  • Badawi GA, Abd El Fattah MA, Zaki HF, El Sayed MI (2017) Sitagliptin and liraglutide reversed nigrostriatal degeneration of rodent brain in rotenone-induced Parkinson’s disease. Inflammopharmacology 25:369–382

    Article  PubMed  CAS  Google Scholar 

  • Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2157

    Article  PubMed  CAS  Google Scholar 

  • Banchroft JD, Stevens A, Turner DR (1996) Theory and practice of histological techniques, 4th edn. Churchill Livingstone, London, pp 257–262

    Google Scholar 

  • Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J, Kortesmaa J, Mercer A, Nielsen E, Ronnholm H, Wikstrom L (2008) Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson’s disease. J Neurosci Res 86:326–338

    Article  PubMed  CAS  Google Scholar 

  • Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306

    Article  PubMed  CAS  Google Scholar 

  • Betarbet R, Sherer TB and Greenamyre JT (2002) Animal models of Parkinson's disease. BioEssays 24:308–318

  • Bido S, Marti M, Morari M (2011) Amantadine attenuates levodopa-induced dyskinesia in mice and rats preventing the accompanying rise in nigral GABA levels. J Neurochem 118:1043–1055

    Article  PubMed  CAS  Google Scholar 

  • Bisaglia M, Mammi S, Bubacco L (2007) Kinetic and structural analysis of the early oxidation products of dopamine: analysis of the interactions with alpha-synuclein. J Biol Chem 282:15597–15605

    Article  PubMed  CAS  Google Scholar 

  • Bisaglia M, Tosatto L, Munari F, Tessari I, de Laureto PP, Mammi S, Bubacco L (2010) Dopamine quinones interact with alpha-synuclein to form unstructured adducts. Biochem Biophys Res Commun 394:424–428

    Article  PubMed  CAS  Google Scholar 

  • Boyce S, Rupniak NM, Steventon MJ, Iversen SD (1990) Nigrostriatal damage is required for induction of dyskinesia by L-DOPA in squirrel monkeys. Clin Neuropharmacol 13:448–458

    Article  PubMed  CAS  Google Scholar 

  • Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT (2009) A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis 34:279–290

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Carlsson A (2002) Treatment of Parkinson’s with L-DOPA. The early discovery phase, and a comment on current problems. J Neural Transm 109:777–787

    Article  PubMed  CAS  Google Scholar 

  • Connolly BS, Lang AE (2014) Pharmacological treatment of Parkinson disease. JAMA 311:1670–1683

    Article  PubMed  CAS  Google Scholar 

  • Cork SC, Richards JE, Holt MK, Gribble FM, Reimann F, Trapp S (2015) Distribution and characterisation of glucagon-like peptide-1 receptor expressing cells in the mouse brain. Mol Metab 4:718–731

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dexter DT, Jenner P (2013) Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med 62:132–144

    Article  PubMed  CAS  Google Scholar 

  • Di Monte DA, McCormack A, Petzinger G, Janson AM, Quik M, Langston WJ (2000) Relationship among nigrostriatal denervation, parkinsonism, and dyskinesia in the MPTP primate model. Mov Disord 15:459–466

    Article  PubMed  Google Scholar 

  • Dodel RC, Berger K, Oertel WH (2001) Health-related quality of life and healthcareutilisation in patients with Parkinson’s disease: impact of motor fluctuations and dyskinesias. PharmacoEconomics 19:1013–1038

    Article  PubMed  CAS  Google Scholar 

  • Dos-Santos-Pereira M, da-Silva CA, Guimaraes FS, Del-Bel E (2016) Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: possible mechanism of action. Neurobiol Dis 94:179–195

    Article  PubMed  CAS  Google Scholar 

  • Elsworth JD, Roth RH (1997) Dopamine synthesis, uptake, metabolism, and receptors: relevance to gene therapy of Parkinson’s disease. Exp Neurol 144:4–9

    Article  PubMed  CAS  Google Scholar 

  • Fabbrini G, Brotchie JM, Grandas F, Nomoto M, Goetz CG (2007) Levodopa-induced dyskinesia. Mov Disord 22:1379–1389

    Article  PubMed  Google Scholar 

  • Fahn S (2000) The spectrum of levodopa-induced dyskinesia. Ann Neurol 47:S2–S9 discussion S9–11

    Article  PubMed  CAS  Google Scholar 

  • Gao HM, Hong JS, Zhang W, Liu B (2002) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 22:782–790

    Article  PubMed  CAS  Google Scholar 

  • Gibb WR, Lees AJ (1988) A comparisons of clinical and pathological features of young and old-onset Parkinson’s disease. Neurology 38:1402–1406

    Article  PubMed  CAS  Google Scholar 

  • Guridi J, Gonzalez-Redondo R, Obeso JA (2012) Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias in Parkinson’s disease. Parkinsons Dis 2012:943159

  • Haining RL, Achat-Mendes C (2017) Neuromelanin, one of the most overlooked molecules in modern medicine, is not a spectator. Neural Regen Res 12:372–375

    Article  PubMed  PubMed Central  Google Scholar 

  • Hamilton A, Patterson S, Porter D, Gault VA, Holscher C (2011) Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain. J Neurosci Res 89:481–489

    Article  PubMed  CAS  Google Scholar 

  • Harkavyi A, Whitton PS (2010) Glucagon-like peptide 1 receptor stimulation as a means of neuroprotection. Br J Pharmacol 159:495–501

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS (2008) Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson’s disease. J Neuroinflammation 5:19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hirsch EC, Hunot S, Damier P, Faucheux B (1998) Glial cells inflammation in Parkinson’s disease: a role in neurodegeneration? Ann Neurol 4:S115–S120

    Article  Google Scholar 

  • Hunter K, Holscher C (2012) Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci 13:33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • ILAR (1996) Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington

  • Jenner P (2003) The MPTP-treated primate as a model of motor complications in PD: primate model of motor complications. Neurology 61:S4–S11

    Article  PubMed  CAS  Google Scholar 

  • Jenner P (2008) Molecular mechanisms of L-DOPA-induced dyskinesia. Nat Rev Neurosci 9:665–677

    Article  PubMed  CAS  Google Scholar 

  • Kabel AM, Omar MS, Alhadhrami A, Alharthi SS, Alrobaian MM (2018) Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical immunohistochemical changes in experimentally-induced parkinsonism: role of toll-like receptor 4, TGF-beta1, NF-kappaB glucagon-like peptide 1. Physiol Behav 188:108–118

    Article  PubMed  CAS  Google Scholar 

  • Kandil EA, Sayed RH, Ahmed LA, Abd El Fattah MA, El-Sayeh BM (2018) Modulatory role of Nurr1 activation and thrombin inhibition in the neuroprotective effects of dabigatran etexilate in rotenone-induced Parkinson’s disease in rats. Mol Neurobiol 55:4078–4089

    PubMed  CAS  Google Scholar 

  • Kappe C, Tracy LM, Patrone C, Iverfeldt K, Sjoholm A (2012) GLP-1 secretion by microglial cells and decreased CNS expression in obesity. J Neuroinflammation 9:276

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim S, Moon M, Park S (2009) Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson’s disease. J Endocrinol 202:431–439

    Article  PubMed  CAS  Google Scholar 

  • Knott C, Wilkin GP, Stern G (1999) Astrocytes and microglia in the substantia nigra and caudate-putamen in Parkinson’s disease. Parkinsonism Relat Disord 5:115–122

    Article  PubMed  CAS  Google Scholar 

  • Kumar N, Van Gerpen JA, Bower JH, Ahlskog JE (2005) Levodopa-dyskinesia incidence by age of Parkinson’s disease onset. Mov Disord 20:342–344

    Article  PubMed  Google Scholar 

  • Lane EL, Dunnett SB (2010) Pre-treatment with dopamine agonists influence L-dopa mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat. Behav Brain Res 213:66–72

    Article  PubMed  CAS  Google Scholar 

  • Larsson M, Lietzau G, Nathanson D, Ostenson CG, Mallard C, Johansson ME, Nystrom T, Patrone C, Darsalia V (2016) Diabetes negatively affects cortical and striatal GABAergic neurons: an effect that is partially counteracted by exendin-4. Biosci Rep 36:e00421

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee YS, Jun HS (2016) Anti-inflammatory effects of GLP-1-based therapies beyond glucose control. Mediat Inflamm 2016:3094642

    Google Scholar 

  • Lee CS, Cenci MA, Schulzer M, Bjorklund A (2000) Embryonic ventral mesencephalic grafts improve levodopa-induced dyskinesia in a rat model of Parkinson’s disease. Brain 123:1365–1379

    Article  PubMed  Google Scholar 

  • Lee CH, Yan B, Yoo KY, Choi JH, Kwon SH, Her S, Sohn Y, Hwang IK, Cho JH, Kim YM, Won MH (2011) Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia. J Neurosci Res 89:1103–1113

    Article  PubMed  CAS  Google Scholar 

  • Lesser RP, Fahn S, Snider SR, Cote LJ, Isgreen WP, Barrett RE (1979) Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 29:1253–1260

    Article  PubMed  CAS  Google Scholar 

  • Lew M (2007) Overview of Parkinson’s disease. Pharmacotherapy 27:155S–160S

    Article  PubMed  CAS  Google Scholar 

  • Liu W, Jalewa J, Sharma M, Li G, Li L, Holscher C (2015) Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neuroscience 303:42–50

    Article  PubMed  CAS  Google Scholar 

  • Lohr KM, Bernstein AI, Stout KA, Dunn AR, Lazo CR, Alter SP, Wang M, Li Y, Fan X, Hess EJ, Yi H, Vecchio LM, Goldstein DS, Guillot TS, Salahpour A, Miller GW (2014) Increased vesicular monoamine transporter enhances dopamine release opposes Parkinson disease-related neurodegeneration in vivo. Proc Natl Acad Sci U S A 111:9977–9982

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lundblad M, Picconi B, Lindgren H, Cenci MA (2004) A model of L-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Neurobiol Dis 16:110–123

    Article  PubMed  CAS  Google Scholar 

  • Lundblad M, Usiello A, Carta M, Hakansson K, Fisone G, Cenci MA (2005) Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia. Exp Neurol 194:66–75

    Article  PubMed  CAS  Google Scholar 

  • Mahmoud GA, El-Azab MF, Desoky AA, El-Sayed NM, Moustafa YM (2014) Activation of GLP-1R preserves dopaminergic neurons in rotenone-induced parkinsonism. In. 6th International Conference on Natural Toxins 27-B6. Avilable from: https://www.egynattox.com. Accessed 15-16 Dec 2014

  • Miller GW, Erickson JD, Perez JT, Penland SN, Mash DC, Rye DB, Levey AI (1999) Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson’s disease. Exp Neurol 156:138–148

    Article  PubMed  CAS  Google Scholar 

  • Nassar NN, Al-Shorbagy MY, Arab HH, Abdallah DM (2015) Saxagliptin: a novel antiparkinsonian approach. Neuropharmacology 89:308–317

    Article  PubMed  CAS  Google Scholar 

  • Obeso JA, Rodriguez-Oroz MC, Chana P, Lera G, Rodriguez M, Olanow CW (2000) The evolution and origin of motor complications in Parkinson’s disease. Neurology 55:S13–S20 discussion S21–13

    PubMed  CAS  Google Scholar 

  • Olanow CW, Agid Y, Mizuno Y, Albanese A, Bonuccelli U, Damier P, De Yebenes J, Gershanik O, Guttman M, Grandas F, Hallett M, Hornykiewicz O, Jenner P, Katzenschlager R, Langston WJ, LeWitt P, Melamed E, Mena MA, Michel PP, Mytilineou C, Obeso JA, Poewe W, Quinn N, Raisman-Vozari R, Rajput AH, Rascol O, Sampaio C, Stocchi F (2004) Levodopa in the treatment of Parkinson’s disease: current controversies. Mov Disord 19:997–1005

    Article  PubMed  Google Scholar 

  • Opacka-Juffry J, Ashworth S, Ahier RG, Hume SP (1998) Modulatory effects of L-DOPA on D2 dopamine receptors in rat striatum measured using in vivo microdialysis and PET. J Neural Transm 105:349–364

    Article  PubMed  CAS  Google Scholar 

  • Pahwa R, Lyons KE (2009) Levodopa-related wearing-off in Parkinson’s disease: identification and management. Curr Med Res Opin 25:841–849

    Article  PubMed  CAS  Google Scholar 

  • Paille V, Brachet P, Damier P (2004) Role of nigral lesion in the genesis of dyskinesias in a rat model of Parkinson’s disease. Neuroreport 15:561–564

    Article  PubMed  Google Scholar 

  • Park S, Dong X, Fisher TL, Dunn S, Omer AK, Weir G, White MF (2006) Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function. J Biol Chem 281:1159–1168

    Article  PubMed  CAS  Google Scholar 

  • Parthsarathy V, Holscher C (2013) Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLoS One 8:e58784

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Perry T, Greig NH (2005) Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in Alzheimer’s disease. Curr Alzheimer Res 2:377–385

    Article  PubMed  CAS  Google Scholar 

  • Quinn N, Critchley P, Marsden CD (1987) Young onset Parkinson’s disease. Mov Disord 2:73–91

    Article  PubMed  CAS  Google Scholar 

  • Rajput AH, Fenton M, Birdi S, Macaulay R (1997) Is levodopa toxic to human substantia nigra? Mov Disord 12:634–638

    Article  PubMed  CAS  Google Scholar 

  • Rascol O, Payoux P, Ory F, Ferreira JJ, Brefel-Courbon C, Montastruc JL (2003) Limitations of current Parkinson’s disease therapy. Ann Neurol 53(Suppl 3):S3–S12 discussion S12–15

    Article  PubMed  CAS  Google Scholar 

  • Rivas E, de Ceballos ML, Nieto O, Fontenla JA (1999) In vivo effects of new inhibitors of catechol-O-methyl transferase. Br J Pharmacol 126:1667–1673

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schneider JS (1989) Levodopa-induced dyskinesia in parkinsonian monkeys: relationship to extent of nigrostriatal damage. Pharmacol Biochem Behav 34:193–196

    Article  PubMed  CAS  Google Scholar 

  • Sharma JC, Macnamara L, Hasoon M, Vassallo M, Ross I (2006) Cascade of levodopa dose and weight-related dyskinesia in Parkinson’s disease (LD-WD-PD cascade). Parkinsonism Relat Disord 12:499–505

    Article  PubMed  Google Scholar 

  • Sharma AN, Pise A, Sharma JN, Shukla P (2015) Glucagon-like peptide-1 (GLP-1) receptor agonist prevents development of tolerance to anti-anxiety effect of ethanol and withdrawal-induced anxiety in rats. Metab Brain Dis 30:719–730

    Article  PubMed  CAS  Google Scholar 

  • Sulzer D, Zecca L (2000) Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 1:181–195

    Article  PubMed  CAS  Google Scholar 

  • Sulzer D, Bogulavsky J, Larsen KE, Behr G, Karatekin E, Kleinman MH, Turro N, Krantz D, Edwards RH, Greene LA, Zecca L (2000) Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci U S A 97:11869–11874

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Taylor TN, Alter SP, Wang M, Goldstein DS, Miller GW (2014) Reduced vesicular storage of catecholamines causes progressive degeneration in the locus ceruleus. Neuropharmacology 76(Pt A):97–105

    Article  PubMed  CAS  Google Scholar 

  • Teema AM, Zaitone SA, Moustafa YM (2016) Ibuprofen or piroxicam protects nigral neurons and delays the development of l-dopa induced dyskinesia in rats with experimental parkinsonism: influence on angiogenesis. Neuropharmacology 107:432–450

    Article  PubMed  CAS  Google Scholar 

  • Teismann P, Tieu K, Cohen O, Choi DK, Wu DC, Marks D, Vila M, Jackson-Lewis V, Przedborski S (2003) Pathogenic role of glial cells in Parkinson’s disease. Mov Disord 18:121–129

    Article  PubMed  Google Scholar 

  • Toulouse A, Sullivan AM (2008) Progress in Parkinson’s disease—where do we stand? Prog Neurobiol 85:376–392

    Article  PubMed  Google Scholar 

  • von Wrangel C, Schwabe K, John N, Krauss JK, Alam M (2015) The rotenone-induced rat model of Parkinson’s disease: behavioral and electrophysiological findings. Behav Brain Res 279:52–61

    Article  CAS  Google Scholar 

  • Wang Q, Liu Y, Zhou J (2015) Neuroinflammation in Parkinson’s disease and its potential as therapeutic target. Transl Neurodegener 4:19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yulug B, Hanoglu L, Kilic E (2015) The neuroprotective role of vesicular monoamine transporter 2 in neurodegenerative diseases. Med Chem 11:104–108

    Article  PubMed  CAS  Google Scholar 

  • Zaitone SA, Abo-Elmatty DM, Elshazly SM (2012a) Piracetam, vinpocetine ameliorate rotenone-induced parkinsonism in rats. Indian J Pharmacol 44:774–779

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zaitone SA, Abo-Elmatty DM, Shaalan AA (2012b) Acetyl-L-carnitine alpha-lipoic acid affect rotenone-induced damage in nigral dopaminergic neurons of rat brain, implication for Parkinson’s disease therapy. Pharmacol Biochem Behav 100:347–360

    Article  PubMed  CAS  Google Scholar 

  • Zaitone SA, Hammad LN, Farag NE (2013) Antioxidant potential of melatonin enhances the response to L-dopa in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-parkinsonian mice. Pharmacol Rep 65:1213–1226

    Article  PubMed  CAS  Google Scholar 

  • Zecca L, Wilms H, Geick S, Claasen JH, Brandenburg LO, Holzknecht C, Panizza ML, Zucca FA, Deuschl G, Sievers J, Lucius R (2008) Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson’s disease. Acta Neuropathol 116:47–55

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Phillips K, Wielgus AR, Liu J, Albertini A, Zucca FA, Faust R, Qian SY, Miller DS, Chignell CF, Wilson B, Jackson-Lewis V, Przedborski S, Joset D, Loike J, Hong JS, Sulzer D, Zecca L (2011) Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: implications for progression of Parkinson’s disease. Neurotox Res 19:63–72

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Zecca L, Wilson B, Ren HW, Wang YJ, Wang XM, Hong JS (2013) Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death. Front Biosci 5:1–11

    Article  Google Scholar 

  • Zucca FA, Basso E, Cupaioli FA, Ferrari E, Sulzer D, Casella L, Zecca L (2014) Neuromelanin of the human substantia nigra: an update. Neurotox Res 25:13–23

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Alfacure Company (Bader City, Egypt) for kindly providing L-dopa and carbidopa powder.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, El-Arish, Egypt

    Ghada A. Badawi & Moushira I. El Sayed

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Mai A. Abd El Fattah & Hala F. Zaki

Authors
  1. Ghada A. Badawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mai A. Abd El Fattah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hala F. Zaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moushira I. El Sayed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ghada A. Badawi.

Ethics declarations

Conflicts of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Badawi, G.A., Abd El Fattah, M.A., Zaki, H.F. et al. Sitagliptin and Liraglutide Modulate L-dopa Effect and Attenuate Dyskinetic Movements in Rotenone-Lesioned Rats. Neurotox Res 35, 635–653 (2019). https://doi.org/10.1007/s12640-019-9998-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-019-9998-3

Keywords

Search

Navigation