College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Department of Physiology and Pharmacology, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal, 8210, Bangladesh.
Environ Pollut. 2018 Nov;242(Pt B):1871-1879. doi: 10.1016/j.envpol.2018.07.080. Epub 2018 Jul 26.
The widely used Di-(2-ethylhexyl) phthalate (DEHP) has been reported to exhibit ubiquitous environmental and global health hazards. The bioaccumulation and environmental persistence of DEHP can cause serious health hazards in wildlife animals and human. However, DEHP-induced nephrotoxicity in bird is remained unknown. Thus, this study explored the related mechanism of DEHP nephrotoxicity in quail. For this purpose, quail were exposed with DEHP at doses of 0, 250, 500, and 1000 mg/kg body weight daily by gavage administration for 45 days. The results showed that DEHP exposure induced renal injury, oxidative stress, and endoplasmic reticulum (ER) degeneration. Low level DEHP (250 mg/kg) exposure inhibited Nrf2 signaling pathway and induced renal injury via oxidative stress and suppressed the unfolded protein response (UPR) signaling pathway and induced ER stress in the kidney. But surprisingly, high level DEHP (500 mg/kg and 1000 mg/kg) exposure activated Nrf2 and UPR signaling pathways and protected kidney, but they still couldn't resist the toxicity of DEHP. Our study demonstrated that DEHP-induced nephrotoxicity in quail was associated with activating Nrf2-mediated antioxidant defense response and UPR signaling pathway.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种被广泛使用的物质，已被报道具有普遍的环境和全球健康危害。DEHP 的生物蓄积和环境持久性会对野生动物和人类造成严重的健康危害。然而，DEHP 对鸟类的肾毒性作用仍不清楚。因此，本研究探讨了 DEHP 对鹌鹑肾脏毒性的相关机制。为此，鹌鹑通过灌胃暴露于 DEHP，剂量分别为 0、250、500 和 1000mg/kg 体重，每天一次，连续 45 天。结果表明，DEHP 暴露可诱导肾脏损伤、氧化应激和内质网（ER）变性。低水平 DEHP（250mg/kg）暴露通过氧化应激抑制 Nrf2 信号通路并诱导肾脏损伤，同时抑制未折叠蛋白反应（UPR）信号通路并诱导 ER 应激。但令人惊讶的是，高水平 DEHP（500mg/kg 和 1000mg/kg）暴露激活了 Nrf2 和 UPR 信号通路，对肾脏起到了保护作用，但仍无法抵抗 DEHP 的毒性。本研究表明，DEHP 诱导鹌鹑肾脏毒性与激活 Nrf2 介导的抗氧化防御反应和 UPR 信号通路有关。
