Abstract
Objective: Our aim was to assess the effect of different doses of linagliptin with or without L-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice.
Methods: Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + L-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + L-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + L-dopa/Carbidopa + linagliptin 10 mg/kg/day. Striatal dopamine, tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-beta 1), toll-like receptor 4 (TLR4), antioxidant enzymes, adenosine triphosphate (ATP), glucagon-like peptide-1 (GLP-1), receptors of advanced glycation end products (RAGE), nuclear factor (erythroid-derived 2) like 2 (Nrf2), heme oxygenase-1 (HO-1), mitochondria] complex I activity, catalepsy and total swim scores were measured. Also, the substantia nigra was subjected to immunohistochemical examination.
Results: The combination of L-dopa/Carbidopa and linagliptin in a dose-dependent manner resulted in significant improvement of the behavioural changes, striatal dopamine, antioxidant parameters, Nrf2/HO-1 content, GLP-1, ATP and mitochondrial complex I activity with significant decrease in striatal RAGE, TGF-beta 1, TNF-alpha, IL-10, TLR4 and alleviated the immunohistochemical changes better than the groups that received either L-dopa/Carbidopa or linagliptin alone.
Conclusion: The combination of L-dopa/Carbidopa and linagliptin might represent a promising therapeutic modality for management of parkinsonism.