Benzo[alpha]Pyrene (B[a]P) causes toxicity via Cytochrome P450 1A1 (CYP1A1) metabolic activity in the brain. Studies have shown that neuronal IL-2 and TNF-α are associated with the hippocampus development and regulation, but their association with the CYP1A1 activity remains unidentified. Limited action of human placental extract (HPE) in the activation of tissue repair and wound healing is known, but their role in B[a]P clearance in the hippocampus is not known so far. Our study has focused on two novel concepts: (1) association of CYP1A1 activity with the inflammatory response in the brain hippocampus and (2) role of HPE in the immunomodulatory mechanisms in the hippocampus upon B[a]P exposure at cytokine receptor and nuclear level. Intrathecal administration of different concentrations of B[a]P and HPE into male wistar rat pups has been conducted. An increased CYP1A1 activity was observed in the presence of 0.25 μM B[a]P alone but in case of HPE followed by 0.25 μM B[a]P, it was equal to control. Herein we report that 5 μl of 0.1 gm HPE followed by 0.25 μM B[a]P administration enabled down-regulation of IL-2 and TNF-α levels in the hippocampus thereby modulating TNFR2 and IL2Rγc signals via NF-κB activation. Besides, localization of IL-2, TNF-α, IL2Rγc, TNFR1 and TNFR2 in the CA1, CA3 and DG regions of the hippocampus are also depicted. Altogether, these findings will project the clinical importance of HPE in the neuroinflammation suppression in the hippocampus developed due to B[a]P toxicity.
Keywords: Benzo[alpha]Pyrene (B[a]P); Cytochrome P450 1A1 (CYP1A1); Cytokines; Hippocampus; Human placental extract (HPE); Neuroinflammation.
Copyright © 2019. Published by Elsevier B.V.