Abstract：
Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical applied as a plasticizer. As an environmental toxicant, DEHP poses a serious health threat. Many studies have revealed that DEHP can cause lead to various degrees of damage to the kidney. However, the evidence of DEHP-induced renal ferroptosis has not been reported. The purpose of this work was to probe the specific role of lipophagy in DEHP-induced renal injury and to investigate the relationship between lipophagy and ferroptosis. Quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day and 750 mg/kg BW/day) for 45 days. Microstructural and ultrastructural observations showed that DEHP caused damage to glomerular and tubular cells, and autophagy with multilayer structures were observed, suggesting that DEHP can induce lipophagy. The results indicated that the iron homeostasis was abnormal and the lipid peroxidation was increased. SLC7A11 and SLC3A2 were down-regulated. PTGS2, ACSL4 and LPCAT3 were elevated. In conclusion, DEHP could induce lipid peroxidation, lead to ferroptosis, and damage renal cells. Therefore, the relationship between lipophagy and ferroptosis was elucidated, which provided a new basis for intervention and prevention of DEHP increased diseases.
摘要：
邻苯二甲酸二(2-乙基己基)酯(DEHP)是用作增塑剂的合成化学品。作为一种环境毒物，DEHP构成了严重的健康威胁。许多研究表明，DEHP可导致不同程度的肾脏损伤。然而,DEHP诱导的肾脏铁蛋白升高的证据尚未报道。这项工作的目的是探讨吸脂性在DEHP诱导的肾损伤中的具体作用，并探讨吸脂性与铁凋亡之间的关系。鹌鹑用DEHP治疗（250mg/kg体重/天，500mg/kgBW/天和750mg/kgBW/天）持续45天。微观结构和超微结构观察表明DEHP对肾小球和肾小管细胞造成损伤,并观察到具有多层结构的自噬，提示DEHP可以诱导吸脂性。结果表明，铁稳态异常，脂质过氧化增加。SLC7A11和SLC3A2下调。PTGS2、ACSL4和LPCAT3升高。总之,DEHP可以诱导脂质过氧化，导致铁性凋亡，损伤肾细胞.因此,阐明了吸脂性和铁死亡之间的关系，为干预和预防DEHP增加的疾病提供了新的依据。
