Cypermethrin Induces the Activation of Rat Primary Microglia and Expression of Inflammatory Proteins
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Cypermethrin Induces the Activation of Rat Primary Microglia and Expression of Inflammatory Proteins Saumya Mishra1,2 · Charul Rajput1,2 · Mahendra Pratap Singh1,2 Received: 13 July 2020 / Accepted: 8 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Cypermethrin activates microglia, which is found to be decisive in neurodegeneration in the experimental rats. While the involvement of microglial activation in toxicant-induced neurodegeneration is reported, the effect of low concentration of cypermethrin on the expression of inflammatory proteins from the rat primary microglia is not yet properly understood. The study intended to delineate the effect of low concentration of cypermethrin on the expression and release of proteins from the microglia. Rat primary microglial cells were treated with cypermethrin to check the expression of inflammatory proteins. Cypermethrin-treated microglia conditioned media and cells were collected to measure the expression and release of inflammatory proteins. Cypermethrin augmented the protein kinase C-δ (PKC-δ), inducible nitric oxide synthase (iNOS), phosphorylated mitogen-activated protein kinase (MAPK) p38 and p42/44, matrix metalloproteinase (MMP)-3, and MMP-9 levels in the cell lysate and tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in the microglia conditioned media. Pre-treatment with minocycline, a microglial activation inhibitor or rottlerin, a PKC-δ inhibitor, notably reduced the release of TNF-α in the conditioned media and expression of iNOS protein in the microglia. Minocycline reduced the expression of PKC-δ, phosphorylated p38 and p42/44 MAPKs, MMP-3, and MMP-9 proteins in the microglia. While cypermethrintreated conditioned media induced the toxicity in the rat primary neurons, minocycline or rottlerin reduced the cypermethrin treated microglia conditioned media-induced toxicity. The outcomes of the present study suggest that cypermethrin activates microglia and releases TNF-α and IL-1β as well as up-regulates the expression of PKC-δ, iNOS, phosphorylated p38 and p42/44 MAPKs, MMP-3, and MMP-9 proteins, which could contribute to neurodegeneration. Keywords Cypermethrin · Minocycline · Neurotoxicity · Microglia
Introduction Prolonged exposure to outdoor pollutants has been linked with an increased incidence of Parkinson’s disease (PD) in humans (Toro et al. 2019). Although pesticide exposure is implicated in neurodegeneration, precise role of any specific pesticide is not yet unambiguously established owing to the limitations of the epidemiological studies. * Mahendra Pratap Singh [email protected] 1
Toxicogenomics and Predictive Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIRIITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226 001, Uttar Pradesh, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, Uttar Pradesh, India
2
Cypermethrin is a synthetic pesticide and falls under th
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