title: Sitagliptin and liraglutide reversed nigrostriatal degeneration of rodent brain in rotenone-induced Parkinson's disease.
abstract: The present study investigated the possible relationship between pro-inflammatory cytokines and programmed nigral neuronal death in rotenone model of Parkinson's disease (PD). Sitagliptin and liraglutide efficacy to inhibit the inflammatory-apoptotic degenerative process were investigated, too. The experimental PD were induced in male albino rats by ten subcutaneously injections of rotenone (3 mg/kg/day, s.c). All treatment drugs were administered for 16 days after induction of Parkinson rat's model. Sitagliptin and liraglutide were administered in three different dose levels (10-20-30 mg/kg, p.o), (25-50-100 μg/kg, s.c), respectively. Cylindrical and catalepsy tests were used to detect the optimum dose response of each drug. Sitagliptin (30 mg/kg/day, p.o) and liraglutide (50 μg/kg, s.c.) showed statistically significant (p ≤ 0.05) effect on behavioral activity. Where both doses improved the motor performance significantly in comparison with other doses in both cylindrical and catalepsy tests. Furthermore, they reversed rotenone-induced nigral neuronal loss, associated with marked decrease of pro-inflammatory cytokines: interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β1, together with a significant increase of striatal dopamine, nigral glial cell line-derived neurotrophic factor (GDNF), and tyrosine hydroxylase positive (TH+) cells. Moreover, the pro-apoptotic environment in nigrostriatal tissues was abrogated significantly, as the pro-apoptotic protein Bax decreased along with the anti-apoptotic protein Bcl-2 increased. In conclusion, sitagliptin and liraglutide represent a promising strategy to mitigate the progression of PD by their anti-inflammatory, anti-apoptotic neurotrophic and neurogenic mechanistic activities.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Industries, Sinai University, El-Arish, Egypt. ghadaali1986@yahoo.com.
authors.forename: Ghada A
authors.initials: GA
authors.lastname: Badawi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Mai A
authors.initials: MA
authors.lastname: Abd El Fattah
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Hala F
authors.initials: HF
authors.lastname: Zaki
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Industries, Sinai University, El-Arish, Egypt.
authors.forename: Moushira I
authors.initials: MI
authors.lastname: El Sayed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D012377:Rodentia; D012402:Rotenone / Q000494:pharmacology*; D000068900:Sitagliptin Phosphate / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D012402:Rotenone; D000069450:Liraglutide; D014446:Tyrosine 3-Monooxygenase; D000068900:Sitagliptin Phosphate
keywords: Apoptosis; GDNF; IL-1β; IL-6; Liraglutide; PD; Rotenone; Sitagliptin; TGF-β1