Metformin protects rotenone-induced dopaminergic neurodegeneration by reducing lipid peroxidation
PHARMACOLOGICAL REPORTS, cilt.72, sa.5, ss.1397-1406, 2020 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 72 Sayı: 5
- Basım Tarihi: 2020
- Doi Numarası: 10.1007/s43440-020-00095-1
- Dergi Adı: PHARMACOLOGICAL REPORTS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
- Sayfa Sayıları: ss.1397-1406
- Anahtar Kelimeler: Parkinson's disease, Metformin, Rotenone, Lipid peroxidation, PARKINSONS-DISEASE, ALPHA-SYNUCLEIN, MOUSE MODEL, NEUROTOXICITY, EXPOSURE, DAMAGE, ACID
- Akdeniz Üniversitesi Adresli: Evet
Özet
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 alpha-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 alpha-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.