Li Ping, Li Zhi-Hua
Marine College, Shandong University , Weihai, Shandong, China.
Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences , Wuhan, China.
J Toxicol Environ Health A. 2021 Jan 2;84(1):20-30. doi: 10.1080/15287394.2020.1828209. Epub 2020 Oct 5.
Tributyltin (TBT), an organotin compound, is hazardous in aquatic ecosystems. However, the mechanisms underlying TBT-induced central nervous system (CNS) toxicity remain to be determined especially in freshwater aquatic vertebrates. The aim of present study was to investigate the effects of chronic exposure to TBT on brain functions in a freshwater teleost the adult wild-type zebrafish (). Fish were exposed to sublethal concentrations of TBT (10, 100 or 300 ng/L) for 6 weeks. The influence of long-term TBT exposure was assessed in the brain of zebrafish with antioxidant related indices including malondialdehyde (MDA) levels and total antioxidant capacity, neurological parameters such as activities of acetylcholinesterase, and monoamine oxidase as well as levels of nitric oxide, dopamine, 5-hydroxytryptamine. In addition indices related to sensitivity of toxic insult such as cytochrome P450 1 regulation and heat shock protein 70 were determined. The regulation of related genes involved in endoplasmic reticulum stress (ERS), apoptosis and Nrf2 pathway were measured. Adverse physiological and biochemical responses were significantly enhanced in a concentration-dependent manner reflecting neurotoxicity attributed to TBT exposure. Our findings provide further insight into TBT-induced toxicity in wild-type zebrafish. and enhance our understanding of the molecular mechanisms underlying TBT-initiated CNS effects.
三丁基锡(TBT)是一种有机锡化合物,在水生生态系统中具有危害性。然而,TBT诱导中枢神经系统(CNS)毒性的机制仍有待确定,尤其是在淡水水生脊椎动物中。本研究的目的是调查长期暴露于TBT对淡水硬骨鱼成年野生型斑马鱼脑功能的影响。将鱼暴露于亚致死浓度的TBT(10、100或300 ng/L)下6周。通过抗氧化相关指标(包括丙二醛(MDA)水平和总抗氧化能力)、神经学参数(如乙酰胆碱酯酶和单胺氧化酶活性)以及一氧化氮、多巴胺、5-羟色胺水平,评估长期TBT暴露对斑马鱼脑的影响。此外,还测定了与毒性损伤敏感性相关的指标,如细胞色素P450 1调节和热休克蛋白70。测量了内质网应激(ERS)、细胞凋亡和Nrf2途径中相关基因的调控。不良的生理和生化反应以浓度依赖的方式显著增强,反映了TBT暴露所致的神经毒性。我们的研究结果进一步深入了解了TBT对野生型斑马鱼的毒性作用,并增强了我们对TBT引发的中枢神经系统效应潜在分子机制的理解。