Protection against Neurobehavioral Changes Induced by Bisphenol A during Development in Rats
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 neurobehavioral alterations. Methods: Lactating dams were divided into 5 groups (8 rats/ each). Dams received daily for 21 days (from parturition until weaning) the following: Saline (1 ml/kg, P.O) for control and BPA (40 mg/kg, P.O) either alone or in combination with Zn (20 mg/kg, P.O), Se (0.1 mg/kg, P.O) or both of them. All pups were daily evaluated for physical development and for neurobehavioral development. The performance in behavioral experiments as Neonatal T-maze and Open-field test (OFT) was also examined. Brain homogenates were used to evaluate monoamines level (DA, NE and 5-HT) and oxidative stress markers (SOD, GPX and CAT). Results: Postnatal BPA exposure induced significant prolongation in the time of appearance of downy hair, fur development, ear opening, righting reflex, cliff avoidance, negative geotaxis 25°, palmar grasp and auditory startle in rat pups. BPA also showed significant reduction in the number of correct choices in T-maze as well as in ambulation frequencies in OFT while showed significant elevation in rearing frequencies and latency time of rat pups. There was also significant reduction in the brain oxidative stress markers (SOD, GPX and CAT) as well as in NE and 5-HT in addition to significant elevation in DA content. On the other hand, Zn and/ or Se co-administration with BPA improved physical and neurobehavioral development as well as performance of pups in the behavioural experiments. They also showed significant elevation in the brain oxidative stress markers (SOD, GPX and CAT), NE and 5-HT levels while significant reduction in the brain DA content as compared to BPA alone. There was significant elevation in the number of correct choices in Zn treated group only. Co-administration of Zn and Se has no more pronounced effect than each one alone except in the effect on brain monoamines and oxidative stress markers. Conclusion: Postnatal BPA exposure delayed some aspect of physical and neurobehavioral development as well as behavioural functions as learning, locomotors and exploratory activities, in addition to emotionality disturbance. Zn and/or Se can protect against BPA-induced alterations. The protective effect of Zn either alone or in combination was more pronounced than Se concerning learning and some reflexes. However, the protective effect of Zn and Se combination has more pronounced effect regarding brain monoamines level and oxidative stress markers only than each of them alone.
Azza A Ali, Engy M El Morsy, Gehad A Abdel-Jaleel, Hemat A Elariny and Marwa Shamseldeen