Silymarin prevents apoptosis through inhibiting the Bax/caspase-3 expression and suppresses toll like receptor-4 pathway in the SNc of 6-OHDA intoxicated rats

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Rasool HaddadiShahla Eyvari Brooshghalan

Abstract

Several lines of evidence show that apoptosis, oxidative stress and neuroinflammation are associated with the development of Parkinson's disease (PD). In the present study, we investigated the effect of pre-treatment with silymarin (SM) on oxidative stress, apoptosis and toll-like receptor 4 (TLR4) expression in substantia nigra pars copmacta (SNc) of 6-hydroxydopamine (6-OHDA)-lesioned rats. Animals were pretreated with 100, 200 or 300 mg/kg of SM daily for 5 days and at 6th day 6-OHDA (8 μg/2 μl) was infused unilaterally into the central region of the SNc. 6-OHDA decreased the total glutathione and antioxidant enzymes activity in the SNc. Interestingly, we found that 6-OHDA caused to TLR4 up regulation. The SNc levels of glutathione, superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase were significantly higher in the SM pretreated rats. SM strongly decreased 6-OHDA-induced elevation of SNc apoptosis, caspase-3 and Bax/Bcl-2 ratio. Furthermore, SM markedly (p < 0.001) prevented from SNc over expression of TLR4 caused by 6-OHDA. A significantly high positive correlation was seen between TLR4 activity with caspase-3 protein levels (r = 0.896, P < 0.01), Bax protein levels (r = 0.96, P < 0.01). Pre-tr...Continue Reading

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Citations

Apr 17, 2020·Current Topics in Medicinal Chemistry·Gagandeep MaanAwanish Mishra
Jun 9, 2018·International Journal of Molecular Sciences·Valentina Caputi, Maria Cecilia Giron
Nov 17, 2019·Journal of Molecular Neuroscience : MN·Manish Kumar TripathiMahendra Pratap Singh
Jul 28, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Rasool HaddadiSara Ami Ahmadi
Oct 30, 2018·BioMed Research International·Flávio Fernandes Veloso BorgesLee Chen-Chen

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