Li Zekun, Jia Kun, Chen Xiaomei, Guo Jun, Zheng Zhiguo, Chen Weihua, Peng Yuan, Yang Yuhao, Lu Huiqiang, Yang Jian
Department of Endodontics, Affiliated Stomatological Hospital, Nanchang University, Nanchang 330006, Jiangxi, China; Jiangxi Key Laboratory of Oral Biomedicine, Jiangxi Clinical Medical Research Center of Oral Diseases, Nanchang 330006, Jiangxi,China.
Center for Drug Screening and Research, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou 341000, Jiangxi, China; School of Marine Sciences, Ningbo University, Ningbo 315211, China.
Ecotoxicol Environ Saf. 2023 Oct 15;265:115523. doi: 10.1016/j.ecoenv.2023.115523. Epub 2023 Sep 28.
Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish (Danio rerio) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.
对羟基苯甲酸丁酯（BuP）是一种常见的抗菌防腐剂，广泛应用于食品、医疗用品、化妆品和个人护理产品中。本研究报告了利用斑马鱼（Danio rerio）胚胎来调查暴露于BuP所引起的潜在发育毒性。在斑马鱼胚胎原肠胚形成过程中，神经嵴细胞（NCCs）的发育非常活跃。因此，我们按照国际安全标准剂量，分别使用了0.5毫克/升、0.75毫克/升和1毫克/升的BuP溶液。在暴露5天后，我们观察到斑马鱼幼体出现严重的颅面软骨畸形、眼周水肿、心脏发育异常和耳石发育延迟。氧化应激反应显著增强。此外，生化分析表明，与对照组相比，过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的活性显著降低，而丙二醛（MDA）的浓度显著升高。此外，成骨细胞活性标志物碱性磷酸酶（ALP）的活性也降低。而且，RT-qPCR结果表明，软骨细胞标志物基因sox9a、sox9b和col2a1a的表达下调。此外，斑马鱼幼体上颌面部软骨细胞的形态发生改变，颅神经嵴细胞的增殖受到抑制。因此，我们的研究结果表明，BuP诱导的强烈氧化应激抑制了斑马鱼幼体神经嵴细胞的增殖，导致颅面畸形。
