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: Ashish Singh, Pratibha Tripathi, Om Prakash, Mahendra Pratap Singh
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 53 Issue 10 Pg. 6849-6858 (12 2016) ISSN: 1559-1182 [Electronic] United States
• PMID: 26660326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Nitrites
• Pyrethrins
• cypermethrin
• Tyrosine 3-Monooxygenase
• Mitogen-Activated Protein Kinases
• Dopamine
• Ibuprofen

Topics

• Animals
• Behavior, Animal
• Dopamine (metabolism)
• Dopaminergic Neurons (drug effects, metabolism, pathology)
• Ibuprofen (pharmacology, therapeutic use)
• Inflammation Mediators (metabolism)
• Lipid Peroxidation (drug effects)
• Male
• Microglia (drug effects, metabolism, pathology)
• Mitogen-Activated Protein Kinases (metabolism)
• Models, Biological
• Motor Activity (drug effects)
• Nerve Degeneration (drug therapy, pathology, physiopathology)
• Nitrites (metabolism)
• Pyrethrins (toxicity)
• Rats
• Substantia Nigra (drug effects, pathology, physiopathology)
• Tyrosine 3-Monooxygenase (metabolism)