Neurotoxicity of Bisphenol A and the Impact of Melatonin Administration on Oxidative Stress, ERK/NF-kB Signaling Pathway, and Behavior in Rats (original) (raw)
Related papers
Effects of Bisphenol A on Oxidative Stress in the Rat Brain
Antioxidants
We investigated the effect of bisphenol A (BPA) on oxidative stress and tau-related proteins in adult rat brains. BPA (10 mg/L) was administered to rats for eight weeks through their drinking water. The reactive oxygen species (ROS) scavenging capacity for hydroxyl radicals in the plasma was reduced after two weeks. In the hippocampus, four and eight weeks of BPA increased the ratio of oxidized DJ-1/DJ-1 (PARK7). The ratio of phosphorylated-GSK3β/GSK3β and phosphorylated-AKT/AKT increased after one week of BPA treatment. The ratio of phosphorylated JNK/JNK and phosphorylated-ERK/ERK increased after eight weeks of BPA; the elevation could be related to tau phosphorylation. Protein phosphatase 2A (PP2A) in the hippocampus decreased after eight weeks of BPA treatment. At that time, SOD1 was significantly induced, but no changes in SOD2 expression were apparent in the hippocampus. Furthermore, the ratio of phosphorylated-tau (PHF-1, Ser396/ Ser404) to total tau level did not change. How...
Behavioral and Brain Functions, 2019
Background: Bisphenol A (BPA), a major endocrine disruptor and a xenobiotic compound is used abundantly in the production of polycarbonate plastics and epoxy resins. Human exposure to this compound is primarily via its leaching from the protective internal epoxy resin coatings of containers into the food and beverages. In addition, the plastics used in dental prostheses and sealants also contain considerable amount of BPA and have a high risk of human exposure. Since it is a well-known endocrine disruptor and closely mimics the molecular structure of human estrogen thereby impairing learning and memory. Withania somnifera (Ws), commonly known as Ashwagandha is known for its varied therapeutic uses in Ayurvedic system of medicine. The present study was undertaken to demonstrate the impairment induced by BPA on the spatial learning, working memory and its alleviation by Ws in Swiss albino mice. The study was conducted on thirty Swiss albino mice, randomly distributed among three groups: control, BPA and BPA + Ws. The behavioral recovery after treatment with Ws was investigated using the Y-maize and Morris water maize test. Whereas, for the estimation of recovery of NMDA receptor which is related to learning and memory in hippocampus region by western blot and immunohistochemistry. Furthermore, the oxidative stress and antioxidant level was assessed by biochemical tests like MDA, SOD and catalase. Results: The study revealed that administration of Ws alleviated the behavioral deficits induced by BPA. Alongside, Ws treatment reinstated the number of NMDA receptors in hippocampus region and showed anti-oxidative property while ameliorating the endogenous anti-oxidant level in the brain. Conclusion: These findings suggest that Ws significantly ameliorates the level of BPA intoxicated oxidative stress thereby potentially treating cognitive dysfunction which acts as the primary symptom in a number of neurodegenerative diseases.
Protection against Neurobehavioral Changes Induced by Bisphenol A during Development in Rats
2017
Background: Bisphenol A (BPA) is an environmental estrogenic pollutant It is used in the manufacture of plastic products including beverages, dental materials and baby bottles. Exposure to BPA is unavoidable and recognized as major public health risk particularly in developing countries. Critical effects of BPA toxicity mostly occur during fetal development and postnatal development. Zinc (Zn) is an essential element for the endogenous enzymatic antioxidant processes. It is required for cell proliferation, differentiation, normal growth, immune functions and wound healing. Selenium (Se) is also nutritionally essential element with antioxidant potential. It protects brain from oxidative damage in various models of neurodegeneration. Objective: To investigate the influence of postnatal BPA exposure during lactation on the neonates of exposed rats as well as to investigate and compare the possible protective role of Zn and/ or Se against postnatal BPA- induced developmental and neurobe...
The protective effect of α-lipoic acid against bisphenol A-induced neurobehavioral toxicity
Neurochemistry international, 2018
Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100 μM) protected cells from BPA (30 μM)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50 mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10 mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effect...
Journal of Neuroscience Research, 2008
In the present study, we investigated the neurotoxicity of bisphenol A [BPA; 2,2-bis-(4 hydroxyphenyl) propane] and the underlying mechanisms of action in mouse hippocampal HT-22 cells. BPA, known to be a xenoestrogen, is used in the production of water bottles, cans, and teeth suture materials. BPA-treated HT-22 cells showed lower cell viability than did controls at concentrations of BPA over 100 μM. BPA induced apoptotic cell death as indicated by staining with Hoechst 33258, costaining with Annexin V/propidium iodide, and activation of caspase 3. BPA regulated the generation of reactive oxygen species (ROS) by increasing intracellular calcium. BPA activated phosphorylation of extracellular signal–regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor (NF)-κB. Pretreatment with specific inhibitors for calcium, ROS, ERK, and JNK decreased BPA-induced cell death; however, inhibitor for NF-κB increased BPA-induced cell death. The results suggest that calcium, ROS, ERK, and JNK are involved in BPA-induced apoptotic cell death in HT-22 cells. In contrast, an NF-κB cascade was activated for survival signaling after BPA treatment. © 2008 Wiley-Liss, Inc.
Exposure to bisphenol A appears to impair hippocampal neurogenesis and spatial learning and memory
Food and Chemical Toxicology, 2011
Bisphenol A (BPA) is widely used in the manufacture of plastics and epoxy resins, and is known to affect reproductive organ growth and development. However, the effects of BPA on hippocampal neurogenesis are unclear in young adult mice. Therefore, the present study was conducted to examine the effects of BPA on hippocampal neurogenesis and learning as well as memory performance in young adult mice. BPA (1, 5, and 20 mg/kg/day) was administered orally to mice for 2 weeks. It was found that high-dose BPA (20 mg/kg/day) decreased the number of newly generated cells in hippocampus, but that low-dose BPA (1 mg/kg) increased the survival of newly generated cells in hippocampi of young mice. Furthermore, high-dose BPA (20 mg/kg/day) was found to impair learning and memory performance significantly. However, no significant differences were observed between high-and low-dose treated mice in terms of levels of brain-derived neurotrophic factor (BDNF) or reactive oxygen species production in hippocampus. In addition, BPA treatment did not induce neuronal loss or damage or astrocyte activation. These data suggest that exposure to BPA causes fluctuations in hippocampal neurogenesis in young adult mice that result in spatial learning and memory impairment via a BDNF-independent pathway.
Endocrinology, 2016
A n increasing body of literature suggests that perinatal exposure to low doses of bisphenol A (BPA) has lasting effects on brain development and/or behavior in rodents (1, 2). Concerns about the occurrence of similar effects in humans are based on the parallel increase of neurobehavioral conditions in humans that appear in rodents exposed to BPA (3), and on epidemiological studies (4). In their recent article, Franssen et al (5) demonstrated opposite dose-dependent effects of BPA on the neuroendocrine maturation of female rats exposed during early life from postnatal day (PND)1 to PND15. In animals exposed to a 0.025-g BPA/kg bw (body weight)/d dose, neuroendocrine maturation related to puberty was found to be delayed, with opposite effects observed in animals exposed to a 5000-g BPA/kg bw/d dose. Modulation of inhibitory ␥-aminobutiric acid (GABA)ergic neurotransmission was found to be associated with the delayed maturation of GnRH secretion through increased GABAergic tone for the 0.025-g BPA/kg bw/d dose; opposite effects were observed for the higher dose. These new findings prompted us to reexamine in more detail our results obtained for male mice exposed to very low doses of BPA from gestational day 8 to PND16 (maternal exposure to 0-, 0.025-, 0.25-, or 25-g BPA/kg bw/d) (6). In this 2013 study, we used untargeted 1 H-nuclear magnetic resonance (NMR) metabolomics to explore the metabolites present in a set of tissues, including male brains at PND21. All brain metabolites were included in a partial least square-dis
Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats
Toxicological Sciences, 2010
This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F 1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concentrations of 0 (control), 0.15, 1.5, 75, 750, and 2250 ppm daily from gestation day 0 through lactation day 21. F 1 offspring were evaluated using the following tests: detailed clinical observations (postnatal days [PNDs] 4, 11, 21, 35, 45, and 60), auditory startle (PNDs 20 and 60), motor activity (PNDs 13, 17, 21, and 61), learning and memory using the Biel water maze (PNDs 22 and 62), and brain and nervous system neuropathology and brain morphometry (PNDs 21 and 72). For F 1 offspring, there were no treatment-related neurobehavioral effects, nor was there evidence of neuropathology or effects on brain morphometry. Based on maternal and offspring body weight reductions, the no-observed-adverse-effect level (NOAEL) for systemic toxicity was 75 ppm (5.85 and 13.1 mg/kg/day during gestation and lactation, respectively), with no treatment-related effects at lower doses or nonmonotonic dose responses observed for any parameter. There was no evidence that BPA is a developmental neurotoxicant in rats, and the NOAEL for developmental neurotoxicity was 2250 ppm, the highest dose tested (164 and 410 mg/kg/day during gestation and lactation, respectively).
Prophylactic Actions of Melatonin in Oxidative Neurotoxicity
Annals of The New York Academy of Sciences, 1997
The central nervous system frequently suffers badly from oxidative damage, and a variety of specific neurological diseases, especially in the aged, are at least in part related to the destructive effects of free radicals.' Neural tissue incurs damage more frequently than other organs because of its high susceptibility to free radical damage and oxidative attack. The reasons for this are severalfold. Firstly, the utilization of molecular oxygen (dioxygen or 02), a molecule that gives rise to many of the most damaging free radicals,2 by the brain is far greater than that for any other organ and the polyunsaturated fatty acid (PUFA) concentration of neural tissue is high? the susceptibility of PUFA to oxidative damage is well known to be high! Additionally, the brain contains elevated concentrations of iron and ascorbic acid, both of which can favor the production of free radicals. Any chemical that increases free radical generation is obviously prooxidative even when the molecule may, under other conditions, have antioxidative properties, e.g., ascorbic acid.5