Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A in rats

Abstract

Bisphenol A (BPA) is used to produce polycarbonate plastic and epoxy resins which are used in many consumer products. Most people encounter BPA in their daily routines. However, it has been heavily reported that BPA has a neurotoxic effect. The present study aimed to investigate the effect of lycopene on cognitive deficits induced by a high dose of BPA focusing on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, oxidative stress, apoptosis, and memory retrieval in adult male rats. Therefore, 72 rats were divided into four groups: control group, BPA group (50 mg/kg body weight (bw)) 3 days a week for 42 days, lycopene group (10 mg/kg bw) daily for 42 days, and lycopene + BPA group. Concurrent treatment of lycopene with BPA improved the learning and cognition memory in Morris water maze and novel object recognition tests along with an increase in acetylcholine esterase activity as well as inhibition of oxidative stress by restoring reduced glutathione and suppressing malondialdehyde hippocampal level to their normal levels. Mechanistically, lycopene upregulated the protein expression of tyrosine receptor kinase B, which resulted in an upsurge in its downstream cascades MAPK/ERK1/2/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of BPA-intoxicated rats. Furthermore, concurrent treatment of lycopene with BPA prevented apoptosis by marked decrease in Bcl-2 associated X protein (Bax) gene expression and caspase 3 activity while restoring B-cell leukemia/lymphoma-2 (Bcl-2) gene expression. In conclusion, the present study provided evidence that lycopene exerted a neuroprotective effect against BPA intoxication in hippocampi of rats via its antioxidant properties, activation of MAPK/ERK pathway, and inhibiting a neuronal apoptosis which reflected on improving the learning and cognition memory.

Ameliorative effects of ceftriaxone sodium combined with dexamethasone on infantile purulent meningitis and associated effects on brain‑derived neurotrophic factor levels

“…Previous studies have demonstrated that BDNF can regulate the expression of cortical neurons and hippocampal neurons through the MARK/ERK pathway (30,31). Although it could be speculated that dexamethasone inhibited the MAPK/ERK pathway, further research is required to explore the intracellular mechanism of BDNF action.…”

“…This was speculated to be a reason for the higher BDNF levels observed in the combination group compared with the monotherapy group in the present study. Previous studies have demonstrated that BDNF can regulate the expression of cortical neurons and hippocampal neurons through the MARK/ERK pathway ( 30 , 31 ). Although it could be speculated that dexamethasone inhibited the MAPK/ERK pathway, further research is required to explore the intracellular mechanism of BDNF action.…”

Role of Antioxidants in Alleviating Bisphenol A Toxicity

“…It can cross the blood-brain barrier, which explains its ability to trap ROS, protecting the cell against oxidative stress, and reducing the damage to cellular components. Lycopene protects the hippocampus against BPA-induced neurotoxicity by inhibiting the oxidative stress, improving cellular signalling, suppressing neural apoptosis, and boosting synaptic plasticity in rat [66]. While BPA deceases the levels of enzyme antioxidants, increasing oxidative stress, decrease in body/organ weight and causing testicular damage in rat, lycopene treatment of BPA-exposed rat enhances the body/organ weight, enzymatic antioxidant activity and reduces the oxidative stress.…”

Anti-Apoptotic Effects of Carotenoids in Neurodegeneration

“…Additionally, Akt was previously shown to upregulate expression of the Bcl-2 gene by activating the cAMP-response element (CRE) [100], and Nrf2 [101] bind directly to the Bcl-x gene, contributing to the retention of protective Bcl-2 and Bcl-xL. Lycopene also activates the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) pathway in the brain [102]. The MAPK/Erk pathway (Figure 1) includes a series of kinase activities including a serine/threonine-specific protein kinase Raf, mitogen-activated protein kinase kinase (MEK/MAPKK), and Erk.…”