Fishery Resources and Environmental Science Experimental Station of The Upper-Middle Reaches of Yangtze River (Ministry of Agriculture), Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, Hubei 430223, China.
Fishery Resources and Environmental Science Experimental Station of The Upper-Middle Reaches of Yangtze River (Ministry of Agriculture), Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, Hubei 430223, China; College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
Ecotoxicol Environ Saf. 2022 Jul 1;239:113614. doi: 10.1016/j.ecoenv.2022.113614. Epub 2022 May 11.
N-isopropyl-N-phenyl-1,4-phenylenediamine (IPPD) is used as a ubiquitous antioxidant worldwide, it is an additive in tire rubber easily discharged into the surrounding environment. At present, there is no study concerning the subacute toxicity of IPPD on fish. We used zebrafish embryos (2 h post-fertilization) exposed to IPPD for 5 days at concentrations of 0, 0.0012, 0.0120 and 0.1200 mg/L to investigate its toxic effects of embryonic development, disruption of growth hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) axis. The results showed that IPPD exposure decreased hatchability, weakened movement ability, reduced body length, and caused multiple types of deformities in zebrafish embryos. The expression of genes involved to GH/IGF and HPT axis were altered after exposure to IPPD in zebrafish larvae. Meanwhile, exposure to IPPD significantly decreased thyroxine (T4) and 3,5,3'-triiodothyronine (T3) contents in larvae, which indicated that HPT axis was in a disturbed state. Moreover, treatment of IPPD decreased the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as levels of glutathione (GSH). While the contents of malondialdehyde (MDA) were elevated after exposure to IPPD. The present study thus demonstrated that IPPD induced oxidative stress, caused developmental toxicity and disrupted the GH/IGF and HPT axis of zebrafish, which could be responsible for developmental impairment and growth inhibition.
N-异丙基-N-苯基-1,4-苯二胺（IPPD）作为一种普遍存在的抗氧化剂在全世界范围内使用，它是轮胎橡胶中的一种添加剂，很容易排放到周围环境中。目前，尚无关于 IPPD 对鱼类亚急性毒性的研究。我们使用斑马鱼胚胎（受精后 2 小时）在浓度为 0、0.0012、0.0120 和 0.1200mg/L 的 IPPD 中暴露 5 天，以研究其对胚胎发育、生长激素/胰岛素样生长因子（GH/IGF）和下丘脑-垂体-甲状腺（HPT）轴的毒性作用。结果表明，IPPD 暴露降低了孵化率，削弱了运动能力，减少了体长，并导致斑马鱼胚胎出现多种畸形。暴露于 IPPD 后，斑马鱼幼虫中涉及 GH/IGF 和 HPT 轴的基因表达发生改变。同时，暴露于 IPPD 显著降低了幼虫中的甲状腺素（T4）和 3,5,3'-三碘甲状腺原氨酸（T3）含量，表明 HPT 轴处于紊乱状态。此外，IPPD 处理降低了超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的酶活性以及谷胱甘肽（GSH）的水平。而暴露于 IPPD 后丙二醛（MDA）的含量升高。本研究表明，IPPD 诱导了氧化应激，导致了斑马鱼的发育毒性和 GH/IGF 和 HPT 轴的破坏，这可能是导致发育损伤和生长抑制的原因。
