title: Ibuprofen abates cypermethrin-induced expression of pro-inflammatory mediators and mitogen-activated protein kinases and averts the nigrostriatal dopaminergic neurodegeneration.
abstract: Cypermethrin induces oxidative stress, microglial activation, inflammation and apoptosis leading to Parkinsonism in rats. While ibuprofen, a non-steroidal anti-inflammatory drug, relieves from inflammation, its efficacy against cypermethrin-induced Parkinsonism has not yet been investigated. The study aimed to explore the protective role of ibuprofen in cypermethrin-induced Parkinsonism, an environmentally relevant model of Parkinson's disease (PD), along with its underlying mechanism. Animals were treated with/without cypermethrin in the presence/absence of ibuprofen. Behavioural, immunohistochemical and biochemical parameters of Parkinsonism and expression of pro-inflammatory and pro-apoptotic proteins along with mitogen-activated protein kinases (MAPKs) were determined. Ibuprofen resisted cypermethrin-induced behavioural impairments, striatal dopamine depletion, oxidative stress in the nigrostriatal tissues and loss of the nigral dopamine producing cells and increase in microglial activation along with atypical expression of pro-inflammatory and apoptotic proteins that include cyclooxygenase-2, tumour necrosis factor-α, MAPKs (c-Jun N-terminal kinase, p38 and extracellular signal-regulated kinase), B cell lymphoma 2-associated protein X, tumour suppressor protein p53, cytochrome c and caspase-3 in the nigrostriatal tissue. The results obtained thus demonstrate that ibuprofen lessens inflammation and regulates MAPKs expression thereby averts cypermethrin-induced Parkinsonism.
authors.affiliation: Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Area, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Post Box No. 80, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Singh
authors.affiliation: Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Area, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Post Box No. 80, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221 005, Uttar Pradesh, India.
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.affiliation: Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Area, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Post Box No. 80, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India. mpsingh@iitr.res.in.
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009573:Nitrites / Q000378:metabolism; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D009573:Nitrites; D011722:Pyrethrins; C017160:cypermethrin; D014446:Tyrosine 3-Monooxygenase; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine; D007052:Ibuprofen
keywords: Cypermethrin; Ibuprofen; Non-steroidal anti-inflammatory drug; Parkinson’s disease