Neurotoxicity of Bisphenol A and the impact of melatonin administration on oxidative stress, ERK/NF-kB signaling pathway and behavior in rats

Abstract

Abstract Bisphenol A (BPA) exposure can be associated with neurodevelopmental disorders due to impairment of cell proliferation and synaptic development. Our study evaluated the effects of melatonin (MEL) on ambulatory activity, lipid peroxidation, cytokines, ERK/NF-kB signaling pathway in hippocampus and frontal lobe, and histopathological changes in the hippocampus of the BPA-treated rats. The animals were divided in 4 groups: control, BPA, BPA + MEL I, BPA + MEL II. MEL I (20 mg/kg b.w), and MEL II (40 mg/kg b.w.) were orally administered for 28 days. In the 29th day, BPA (1 mg/kg b.w) was intraperitoneally administered and, after 24 h, Open Field Test (OFT) and Elevated Plus Maze (EPM), were conducted. The results showed that MEL II group made significantly more entries in the open arms of EPM, travelled significantly greater distance and spent more time in the central part of OFT. Malondialdehyde levels were diminished by MEL II in the hippocampus and by MEL I in the frontal lobe. In the hippocampus, MAPK level was significantly lowered by both doses of MEL (p < 0.05) while in frontal lobe, only MEL II reduced the MAPK activation. MEL I and II significantly decreased the γH2AX and upregulated the NFkB and pNFkB expressions in the hippocampus while MEL II downregulated the MCP1 expression. Both doses of MEL attenuated the BPA-evoked histopathological alterations in the hippocampus. These data indicate that MEL can mediate the neuroprotection against BPA-induced neurotoxicity and improves the behavioral changes suggesting a real potential as protective agent in brain toxicity.