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 signi cantly more entries in the open arms of EPM, travelled signi cantly 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 signi cantly lowered by both doses of MEL (p < 0.05) while in frontal lobe, only MEL II reduced the MAPK activation. MEL I and II signi cantly 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.Additionally, BPA exposure increases the expression of proin ammatory cytokines such as IL-6, IL-1 b and TNF-a, reduces the expression of anti-in ammatory IL-10, and induces the activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), some other mitogen-activated protein kinase (MAPK) and nuclear factor (NF -kB) pathway (Inadera 2015; Rebolledo-Solleiro 2021).Several in vivo and in vitro models reported that natural compounds (vitamin A, C and E, Quercetin, Lycopene, Gallic acid, Ginseng, Tualang honey) may alleviate BPA -induced -toxicity (Amjad, 2020). Melatonin (MEL), secreted by the pineal gland in the brain, known for its antioxidant and antiapoptotic effects (Lee 2019; Rehman 2019).Considering that oxidative stress appears to be an important contributor to the neurotoxicity induced by BPA, and the antioxidants, with remarkable neuroprotective effects, could play a valuable protective role, our study aimed to evaluate the effects of MEL preadministration on ambulatory activity, lipid peroxidation, in ammatory cytokines, ERK/NF-kB signaling pathway in hippocampus and frontal lobe and histopathological changes in hippocampus of the BPA -treated rats. The BPA was administered in a single dose in rats treated orally with two doses of MEL for 28 days.÷ ersefunctions, suchas, ∘ adianrhythm, e ≠ rgymηbolism and imμ ≠ systemrega --→ r, hasbeenrep or ted → exert ≠ uroprotect has been identi ed as an important factor to neu...

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.