Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-ß1, NF-κB and glucagon-like peptide 1.
Physiol Behav
; 188: 108-118, 2018 05 01.
Article
em En
| MEDLINE
| ID: mdl-29410018
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; MPTPâ¯+â¯l-dopa/Carbidopa; MPTPâ¯+â¯linagliptin 3â¯mg/kg/day; MPTPâ¯+â¯linagliptin 10â¯mg/kg/day; MPTPâ¯+â¯Carboxymethyl cellulose; MPTPâ¯+â¯l-dopa/Carbidopaâ¯+â¯linagliptin 3â¯mg/kg/day and MPTPâ¯+â¯l-dopa/Carbidopaâ¯+â¯linagliptin 10â¯mg/kg/day. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-ß1), 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), mitochondrial 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-ß1, TNF-α, 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carbidopa
/
Levodopa
/
NF-kappa B
/
Transtornos Parkinsonianos
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Peptídeo 1 Semelhante ao Glucagon
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Receptor 4 Toll-Like
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Fator de Crescimento Transformador beta1
/
Linagliptina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article