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Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson's disease phenotype in the mouse.
J Pineal Res. 2011 Mar; 50(2):97-109.JP

Abstract

Oxidative stress is reported as one of the most widely accepted mechanisms of maneb (MB)- and paraquat (PQ)-induced nigrostriatal dopaminergic neurodegeneration leading to the Parkinson's disease (PD) phenotype. The study investigated the effects of silymarin, an antioxidant of plant origin, and melatonin, an indoleamine produced in all species, in MB- and PQ-induced mouse model of PD. The mice were treated intraperitoneally daily with silymarin (40mg/kg) or melatonin (30mg/kg) along with respective controls for 9wk. Subsets of these animals were also treated with MB (30mg/kg) and PQ (10mg/kg), twice a week, for 9wk, 2hr after silymarin/melatonin treatment. Locomotor activities along with striatal dopamine content, tyrosine hydroxylase (TH) immunoreactivity, number of degenerating neurons, lipid peroxidation and nitrite content were estimated. Additionally, mRNA expression of vesicular monoamine transporter, cytochrome P-450 2E1 (CYP2E1), and glutathione-S-transferase A4-4 (GSTA4-4), catalytic activities of CYP2E1 and GSTA4-4 and protein expressions of unphosphorylated and phosphorylated p53 (p53 and P-p53), Bax and caspase 9 were measured in control and MB- and PQ-treated mice with either silymarin or melatonin treatments. Silymarin/melatonin significantly offset MB- and PQ-mediated reductions in locomotor activities, dopamine content, TH immunoreactivity, VMAT 2 mRNA expression and the expression of p53 protein. Silymarin/melatonin attenuated the increases in lipid peroxidation, number of degenerating neurons, nitrite content, mRNA expressions of cytochrome P-450 2E1 (CYP2E1) and GSTA4-4, catalytic activities of CYP2E1 and GST and P-p53, Bax and caspase 9 protein expressions. The results demonstrate that silymarin and melatonin offer nigrostriatal dopaminergic neuroprotection against MB- and PQ-induced PD by the modulation of oxidative stress and apoptotic machinery.

Authors+Show Affiliations

Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), M. G. Marg, Lucknow, UP, India Jamia Hamdard, New Delhi, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20964710

Citation

Singhal, Naveen Kumar, et al. "Melatonin or Silymarin Reduces Maneb- and Paraquat-induced Parkinson's Disease Phenotype in the Mouse." Journal of Pineal Research, vol. 50, no. 2, 2011, pp. 97-109.
Singhal NK, Srivastava G, Patel DK, et al. Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson's disease phenotype in the mouse. J Pineal Res. 2011;50(2):97-109.
Singhal, N. K., Srivastava, G., Patel, D. K., Jain, S. K., & Singh, M. P. (2011). Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson's disease phenotype in the mouse. Journal of Pineal Research, 50(2), 97-109. https://doi.org/10.1111/j.1600-079X.2010.00819.x
Singhal NK, et al. Melatonin or Silymarin Reduces Maneb- and Paraquat-induced Parkinson's Disease Phenotype in the Mouse. J Pineal Res. 2011;50(2):97-109. PubMed PMID: 20964710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin or silymarin reduces maneb- and paraquat-induced Parkinson's disease phenotype in the mouse. AU - Singhal,Naveen Kumar, AU - Srivastava,Garima, AU - Patel,Devendra Kumar, AU - Jain,Swatantra Kumar, AU - Singh,Mahendra Pratap, Y1 - 2010/10/22/ PY - 2010/10/23/entrez PY - 2010/10/23/pubmed PY - 2011/5/27/medline SP - 97 EP - 109 JF - Journal of pineal research JO - J Pineal Res VL - 50 IS - 2 N2 - Oxidative stress is reported as one of the most widely accepted mechanisms of maneb (MB)- and paraquat (PQ)-induced nigrostriatal dopaminergic neurodegeneration leading to the Parkinson's disease (PD) phenotype. The study investigated the effects of silymarin, an antioxidant of plant origin, and melatonin, an indoleamine produced in all species, in MB- and PQ-induced mouse model of PD. The mice were treated intraperitoneally daily with silymarin (40mg/kg) or melatonin (30mg/kg) along with respective controls for 9wk. Subsets of these animals were also treated with MB (30mg/kg) and PQ (10mg/kg), twice a week, for 9wk, 2hr after silymarin/melatonin treatment. Locomotor activities along with striatal dopamine content, tyrosine hydroxylase (TH) immunoreactivity, number of degenerating neurons, lipid peroxidation and nitrite content were estimated. Additionally, mRNA expression of vesicular monoamine transporter, cytochrome P-450 2E1 (CYP2E1), and glutathione-S-transferase A4-4 (GSTA4-4), catalytic activities of CYP2E1 and GSTA4-4 and protein expressions of unphosphorylated and phosphorylated p53 (p53 and P-p53), Bax and caspase 9 were measured in control and MB- and PQ-treated mice with either silymarin or melatonin treatments. Silymarin/melatonin significantly offset MB- and PQ-mediated reductions in locomotor activities, dopamine content, TH immunoreactivity, VMAT 2 mRNA expression and the expression of p53 protein. Silymarin/melatonin attenuated the increases in lipid peroxidation, number of degenerating neurons, nitrite content, mRNA expressions of cytochrome P-450 2E1 (CYP2E1) and GSTA4-4, catalytic activities of CYP2E1 and GST and P-p53, Bax and caspase 9 protein expressions. The results demonstrate that silymarin and melatonin offer nigrostriatal dopaminergic neuroprotection against MB- and PQ-induced PD by the modulation of oxidative stress and apoptotic machinery. SN - 1600-079X UR - https://www.unboundmedicine.com/medline/citation/20964710/Melatonin_or_silymarin_reduces_maneb__and_paraquat_induced_Parkinson's_disease_phenotype_in_the_mouse_ L2 - https://doi.org/10.1111/j.1600-079X.2010.00819.x DB - PRIME DP - Unbound Medicine ER -