Faculty of Pharmacy, Department of Toxicology, Hacettepe University, Ankara, Turkey.
Faculty of Pharmacy, Department of Toxicology, Çukurova University, Adana, Turkey.
Environ Sci Pollut Res Int. 2021 Jun;28(21):26961-26974. doi: 10.1007/s11356-021-12408-9. Epub 2021 Jan 26.
Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP) are abundant endocrine disrupting chemicals (EDCs). In recent years, studies showed that EDCs may lead to neurodevelopmental diseases. The effects of prenatal exposure to these chemicals may have serious consequences. Moreover, exposure to EDCs as a mixture may have different effects than individual exposures. The present study aimed to determine the toxicity of BPA and/or DEHP on central nervous system (CNS) and neuroendocrine system in prenatal and lactational period in Sprague-Dawley rats. Pregnant rats were randomly divided into four groups: control (received vehicle); BPA group (received BPA at 50 mg/kg/day); DEHP group (received DEHP at 30 mg/kg/day); and combined exposure group (received both BPA at 50 mg/kg/day and DEHP at 30 mg/kg/day) during pregnancy and lactation by oral gavage. At the end of lactation, male offspring (n = 6) were randomly grouped. The alterations in the brain histopathology, neurotransmitter levels and enzyme activities in the cerebrum region, oxidative stress markers, and apoptotic effects in the hippocampus region were determined at adulthood. The results showed that exposure to EDCs at early stages of life caused significant changes in lipid peroxidation, total GSH and neurotransmitter levels, and activities of neurotransmitter-related enzymes. Moreover, BPA and/or DEHP led to apoptosis and histopathologic alterations in the hippocampus. Therefore, we can suggest that changes in oxidant/antioxidant status, as well as in neurotransmitters and related enzymes, can be considered as the underlying neurotoxicity mechanisms of BPA and DEHP. However, more mechanistic studies are needed.
双酚 A（BPA）和邻苯二甲酸二（2-乙基己基）酯（DEHP）是丰富的内分泌干扰化学物质（EDCs）。近年来的研究表明，EDCs 可能导致神经发育疾病。这些化学物质在产前的暴露可能会产生严重的后果。此外，暴露于 EDCs 混合物可能会产生与单独暴露不同的影响。本研究旨在确定 BPA 和/或 DEHP 在产前和哺乳期对 Sprague-Dawley 大鼠中枢神经系统（CNS）和神经内分泌系统的毒性。怀孕的大鼠被随机分为四组：对照组（给予载体）；BPA 组（给予 50mg/kg/天的 BPA）；DEHP 组（给予 30mg/kg/天的 DEHP）；联合暴露组（给予 50mg/kg/天的 BPA 和 30mg/kg/天的 DEHP），通过口服灌胃。哺乳期结束时，雄性幼仔（n=6）被随机分组。在成年时测定大脑组织病理学、大脑区域神经递质水平和酶活性的改变、氧化应激标志物和海马区的凋亡效应。结果表明，生命早期接触 EDCs 会导致脂质过氧化、总 GSH 和神经递质水平以及神经递质相关酶的活性发生显著变化。此外，BPA 和/或 DEHP 导致海马区的凋亡和组织病理学改变。因此，我们可以认为氧化应激/抗氧化状态以及神经递质和相关酶的改变可以被认为是 BPA 和 DEHP 的潜在神经毒性机制。然而，还需要更多的机制研究。
