title: Silymarin- and melatonin-mediated changes in the expression of selected genes in pesticides-induced Parkinsonism.
abstract: Parkinson's disease (PD) is the second most unconcealed neurodegenerative disorder labelled with motor impairments. Two pesticides, manganese ethylene-1,2-bisdithiocarbamate (maneb) and 1,1'-dimethyl-4,4'-bipyridinium dichloride (paraquat), together, are reported to increase the incidence of PD in humans and Parkinsonism in mice. Conversely, silymarin and melatonin, two naturally occurring antioxidants, rescue from maneb- and paraquat-induced Parkinsonism. The study examined silymarin- and melatonin-mediated changes in the expression of selected genes in maneb- and paraquat-induced Parkinsonism employing mouse discover chips microarrays. The mice were treated intraperitoneally (i.p.), daily, with silymarin (40 mg/kg) or melatonin (30 mg/kg) for 9 weeks along with vehicles. Subsets of animals were also treated with maneb (30 mg/kg; i.p.) and paraquat (10 mg/kg; i.p.), twice a week, for 9 weeks. Whilst the expression of genes in the striatum was determined by microarray, the expression of randomly selected transcripts was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Combined maneb- and paraquat-treatment altered the expression of several genes associated with apoptosis, inflammation, cell cycle, cell-signalling, etc. pathways. Silymarin and melatonin significantly resisted the changes in the expression of a few genes related to apoptosis, inflammation, cell cycle, cell-signalling, etc. The expression patterns of seven randomly selected genes were analyzed by qRT-PCR, which were found to follow the similar trends, as observed with microarray. The results obtained from the study thus demonstrate that despite resemblances, silymarin and melatonin differentially offset maneb- and paraquat-induced changes in transcriptome.
authors: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box 80, Lucknow, 226 001, Uttar Pradesh, India.
authors: Naveen Kumar
authors: NK
authors: Singhal
authors: Amit Kumar
authors: AK
authors: Chauhan
authors: Swatantra Kumar
authors: SK
authors: Jain
authors: Rishi
authors: R
authors: Shanker
authors: Chetna
authors: C
authors: Singh
authors: Mahendra Pratap
authors: MP
authors: Singh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000235:genetics; D007473:Ion Channels / Q000235:genetics; D008297:Male; D008344:Maneb / Q000009:adverse effects; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics*; D010575:Pesticides / Q000009:adverse effects*; D015398:Signal Transduction / Q000235:genetics; D012838:Silymarin / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D010575:Pesticides; D012838:Silymarin; D008344:Maneb; D008550:Melatonin; D010269:Paraquat
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