Metformin protects rotenone-induced dopaminergic neurodegeneration by reducing lipid peroxidation.
Pharmacol Rep
; 72(5): 1397-1406, 2020 Oct.
Article
em En
| MEDLINE
| ID: mdl-32207092
ABSTRACT
BACKGROUND:
Metformin, a widely prescribed antidiabetic drug, has been suggested to have a neuroprotective effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. In this study, we investigated the neuroprotective potential of metformin against rotenone-induced dopaminergic neuron damage and its underlying mechanisms.METHODS:
C57BL/6 mice were given saline or rotenone (2.5 mg/kg/day, ip) injection for 10 days. Metformin treatment (300 mg/kg/day, ip) was started concurrently with rotenone administration and continued for 10 days. The neuroprotective effect of metformin on rotenone-induced dopaminergic toxicity was assessed by tyrosine hydroxylase (TH), cleaved caspase-3 and α-synuclein immunohistochemistry in substantia nigra (SN). SN tissues were extracted for biochemical analysis. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) protein levels were measured by spectrophotometric assay.RESULTS:
We found that metformin treatment attenuated the rotenone-induced loss of TH+ neurons in the SN. Additionally, metformin significantly decreased the rotenone-induced increase of cleaved caspase-3 and α-synuclein accumulation in the SN; however, there was no difference in motor behaviours between the experimental groups. Meanwhile, the levels of MDA and 4-HNE in SN were significantly reduced in the rotenone-metformin group compared to the rotenone group.CONCLUSIONS:
Results showed that metformin treatment attenuated dopaminergic neuron loss in SN induced by rotenone by decreasing lipid peroxidation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rotenona
/
Peroxidação de Lipídeos
/
Fármacos Neuroprotetores
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Doenças Neurodegenerativas
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Neurônios Dopaminérgicos
/
Metformina
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Rep
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Turquia