Rasool Haddadi1, Alireza Mohajjel Nayebi2, Shahla Eyvari Brooshghalan3. 1. Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran; Herbal Medicine and natural product Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address: haddadi.r@umsha.ac.ir. 2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: nayebia@tbzmed.ac.ir. 3. Students Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Abstract
BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Pre-treatment of 6-OHDA-lesioned rats with SM reduces SNc neuronal apoptosis possibly through inhibition of TLR4 over expression. Further clinical study should be carried out to prove potential application of SM for protection against PD in susceptible individuals.
BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: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). CONCLUSION: Pre-treatment of 6-OHDA-lesioned rats with SM reduces SNc neuronal apoptosis possibly through inhibition of TLR4 over expression. Further clinical study should be carried out to prove potential application of SM for protection against PD in susceptible individuals.