Di (2-ethylhexyl) phthalate (DEHP) is an environmentally persistent and bioaccumulative plasticizer. Accumulation of DEHP in the body can eventually cause kidney damage. As a type of natural carotenoid, lycopene (LYC) has a potential protective effect on renal cells, but the protective mechanism has not yet been elucidated. The major goal of this study was to see how effective LYC was at treating DEHP-induced nephrotoxicity in mice. ICR mice were treated with DEHP (500 mg/kg BW/day or 1000 mg/kg BW/day) or LYC (5 mg/kg BW/day) for 28 days. Through histopathology and ultrastructure, we found that LYC attenuated DEHP-induced renal tubular cell and glomerular damage. LYC relieved DEHP-induced kidney injury evidenced by lower levels of blood urea nitrogen (Bun), creatinine (Cre), and uric acid (Uric). Meanwhile, the reduced expression of kidney injury molecule-1 (Kim-1) also supported it. Notably, LYC can alleviate the activity or content of cytochrome P450 system (CYP450s) interfered with by DEHP. In addition, LYC treatment reduced nuclear accumulation of DEHP-induced aromatic hydrocarbon receptor (AhR) and AhR nuclear transporter (Arnt), and its downstream target genes such as cytochrome P450-dependent monooxygenase (CYP) 1A1, 1A2, and 1B1 expression significantly decreased to normal in the LYC treatment group. In summary, LYC can mediate the AhR/Arnt signaling system to prevent kidney toxicity in mice caused by DEHP exposure.

中文翻译：

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番茄红素预防 DEHP 诱导的肾细胞损伤是由芳烃受体靶向的

邻苯二甲酸二（2-乙基己基）酯 (DEHP) 是一种环境持久性和生物累积性增塑剂。DEHP 在体内的积累最终会导致肾脏损害。番茄红素（LYC）作为一种天然类胡萝卜素，对肾细胞具有潜在的保护作用，但其保护机制尚未阐明。这项研究的主要目标是了解 LYC 在治疗 DEHP 诱导的小鼠肾毒性方面的效果如何。ICR 小鼠用 DEHP（500 毫克/公斤体重/天或 1000 毫克/公斤体重/天）或 LYC（5 毫克/公斤体重/天）治疗 28 天。通过组织病理学和超微结构，我们发现 LYC 减轻了 DEHP 诱导的肾小管细胞和肾小球损伤。LYC 减轻了 DEHP 引起的肾损伤，这可以通过降低血尿素氮 (Bun)、肌酐 (Cre) 和尿酸 (Uric) 水平来证明。同时，肾损伤分子-1（Kim-1）的表达降低也支持它。值得注意的是，LYC 可以减轻 DEHP 干扰的细胞色素 P450 系统（CYP450s）的活性或含量。此外，LYC处理减少了DEHP诱导的芳香烃受体（AhR）和AhR核转运蛋白（Arnt）的核积累，其下游靶基因如细胞色素P450依赖性单加氧酶（CYP）1A1、1A2和1B1表达显着降低LYC 治疗组正常。总之，LYC 可以介导 AhR/Arnt 信号系统，以防止 DEHP 暴露引起的小鼠肾毒性。LYC 处理减少了 DEHP 诱导的芳香烃受体 (AhR) 和 AhR 核转运蛋白 (Arnt) 的核积累，其下游靶基因如细胞色素 P450 依赖性单加氧酶 (CYP) 1A1、1A2 和 1B1 表达显着降低至正常LYC 治疗组。总之，LYC 可以介导 AhR/Arnt 信号系统，以防止 DEHP 暴露引起的小鼠肾毒性。LYC 处理减少了 DEHP 诱导的芳香烃受体 (AhR) 和 AhR 核转运蛋白 (Arnt) 的核积累，其下游靶基因如细胞色素 P450 依赖性单加氧酶 (CYP) 1A1、1A2 和 1B1 表达显着降低至正常LYC 治疗组。总之，LYC 可以介导 AhR/Arnt 信号系统，以防止 DEHP 暴露引起的小鼠肾毒性。