A Common Carcinogen Benzo[a]pyrene Causes Neuronal Death in Mouse via Microglial Activation

作者: Kallol Dutta , Debapriya Ghosh , Arshed Nazmi , Kanhaiya Lal Kumawat , Anirban Basu

DOI: 10.1371/JOURNAL.PONE.0009984

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摘要: Background Benzo[a]pyrene (B[a]P) belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported probable carcinogen humans. Exposure can take place by ingestion contaminated (especially grilled, roasted or smoked) food water, inhalation polluted air. There are reports available also suggests neurotoxicity result exposure, but exact mechanism action is unknown. Methodology/Principal Findings Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated no direct neurotoxic effect. We utilized both vivo vitro systems demonstrate causes microglial activation. Using showed for first time administration results elevation reactive oxygen species within microglia thereby causing depression antioxidant protein levels; enhanced expression inducible nitric oxide synthase, increased production NO from cells. Synthesis secretion proinflammatory cytokines were elevated microglia, possibly via p38MAP kinase pathway. All these factors contributed bystander death neurons, vitro. When administered animals, was found cause activation astrogliosis brain with subsequent increase cytokine levels. Conclusions/Significance Contrary earlier published activity. However, it kills neurons activating immune cells viz microglia. For time, have provided conclusive evidence regarding which micropollutant may actually damage central nervous system. In today's perspective, where rising pollution levels globally matter grave concern, our study throws light on other health hazards such pollutants exert.

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