College of Chemistry & Environmental Science, Guangdong Ocean University, Zhanjiang 524088, PR China.
College of Animal Science & Technology, Jiangxi Agricultural University, Nanchang 330045, PR China.
Sci Total Environ. 2023 Apr 15;869:161730. doi: 10.1016/j.scitotenv.2023.161730. Epub 2023 Jan 18.
To further explore short-term exposure of enrofloxacin (ENR) induced toxicity in crucian carp brain that has been reported by our previous work, as well as the possible toxicological mechanisms, this study investigated the blood-brain barrier (BBB) permeability to low dosage of ENR through comprehensively assessing expression of BBB constitutive molecules zonula occludens-1 (ZO-1) and permeability glycoprotein (P-gp), as well as ENR residue in brain of crucian carp. Toxicologic effect of ENR on brain tissue was determined through evaluating expression of brain-derived proteins S100B, neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) in crucian carp brain tissue, as well as contents of the proteins in serum. The toxicological mechanisms were explored through analyzing transcriptome analysis data. Results showed that ENR possessed excellent permeability to crucian carp BBB, which was closely related to deranged BBB structure and declined ENR efflux that were attributed to downregulated expression of ZO-1 and P-gp by ENR exposure. Meanwhile, S100B, NSE and GFAP were upregulated in brain by ENR, and came out into blood across the damaged BBB. These data revealed that ENR induced disruption of BBB and damage of brain tissue in crucian carp. Transcriptome analysis data indicated that ENR induced toxicologic effect might be related to modification of metabolism, organismal systems, and genetic information processing, etc., and that PI3K/Akt, MAPK, HIF-1, and ubiquitin mediated proteolysis involved the mechanisms, most of the mechanisms were attributed to ENR induced oxidative stress in crucian carp brain.
为了进一步探索我们之前的工作中报道的恩诺沙星(ENR)对鲫鱼大脑的短期暴露毒性,以及可能的毒理学机制,本研究通过综合评估血脑屏障(BBB)组成分子紧密连接蛋白-1(ZO-1)和通透性糖蛋白(P-gp)的表达,以及鲫鱼大脑中 ENR 的残留量,来研究低剂量 ENR 通过 BBB 的通透性。ENR 对脑组织的毒理作用通过评估鲫鱼脑组织中脑源性蛋白 S100B、神经元特异性烯醇化酶(NSE)和神经胶质纤维酸性蛋白(GFAP)的表达以及血清中这些蛋白的含量来确定。通过分析转录组分析数据来探讨毒理学机制。结果表明,ENR 对鲫鱼 BBB 具有良好的通透性,这与 BBB 结构紊乱和 ENR 外排减少密切相关,而这归因于 ENR 暴露导致 ZO-1 和 P-gp 表达下调。同时,ENR 使 S100B、NSE 和 GFAP 在大脑中上调,并通过受损的 BBB 进入血液。这些数据表明,ENR 诱导鲫鱼 BBB 破坏和脑组织损伤。转录组分析数据表明,ENR 诱导的毒理作用可能与代谢、机体系统和遗传信息处理等的修饰有关,PI3K/Akt、MAPK、HIF-1 和泛素介导的蛋白水解等机制参与其中,其中大多数机制归因于 ENR 在鲫鱼大脑中诱导的氧化应激。