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

  • Ghada A. BadawiEmail author
  • Mai A. Abd El Fattah
  • Hala F. Zaki
  • Moushira I. El Sayed
Original Article
  • 26 Downloads

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.

Keywords

PD Rotenone L-dopa Liraglutide Sitagliptin TH VMAT2 AIMs LID NM 

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

Notes

Acknowledgments

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

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  • Ghada A. Badawi
    • 1
    Email author
  • Mai A. Abd El Fattah
    • 2
  • Hala F. Zaki
    • 2
  • Moushira I. El Sayed
    • 1
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacySinai UniversityEl-ArishEgypt
  2. 2.Department of Pharmacology and Toxicology, Faculty of PharmacyCairo UniversityCairoEgypt

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