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. 2021 Sep 15;285:117080. doi: 10.1016/j.envpol.2021.117080. Epub 2021 Apr 7.
Di (2-ethylhexyl) phthalate (DEHP) is a widespread plasticizer that persists in the environment and can significantly contribute to serious health hazards of liver especially oxidative stress injury. Lycopene (LYC) as a carotenoid has recently gained widespread attention because of antioxidant activity. However, the potential mechanism of DEHP-induced hepatotoxicity and antagonism effect of LYC on it are still unclear. To explore the underlying mechanisms of this hypothesis, the mice were given by gavage with LYC (5 mg/kg) and DEHP (500 or 1000 mg/kg). The data suggested that DEHP caused liver enlargement, reduction of antioxidant activity markers, increase of oxidative stress indicators and disorder of cytochrome P450 enzymes system (CYP450s) homeostasis. DEHP-induced reactive oxygen species (ROS) activated the NF-E2-relatedfactor2 (Nrf2) and nuclear xenobiotic receptors (NXRs) system including Aryl hydrocarbon receptor (AHR), Pregnane X receptor (PXR) and Constitutive androstane receptor (CAR). Interestingly, these disorders and injuries were prevented after LYC treatment. Taken together, DEHP administration resulted in hepatotoxicity including oxidative stress injury and disordered CYP450 system, but these alterations might be ameliorated by LYC via crosstalk between AHR-Nrf2 pathway.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛使用的增塑剂，它在环境中持久存在，并可能对肝脏造成严重的健康危害，特别是氧化应激损伤。番茄红素（LYC）作为一种类胡萝卜素，由于其抗氧化活性，最近受到了广泛关注。然而，DEHP 诱导的肝毒性的潜在机制和 LYC 对其的拮抗作用仍不清楚。为了探索这一假设的潜在机制，将 LYC（5mg/kg）和 DEHP（500 或 1000mg/kg）通过灌胃给予小鼠。数据表明，DEHP 导致肝脏肿大、抗氧化活性标志物减少、氧化应激指标增加和细胞色素 P450 酶系统（CYP450s）稳态失调。DEHP 诱导的活性氧（ROS）激活了 NF-E2 相关因子 2（Nrf2）和核外源受体（NXRs）系统，包括芳香烃受体（AHR）、孕烷 X 受体（PXR）和组成型雄烷受体（CAR）。有趣的是，LYC 处理后，这些紊乱和损伤得到了预防。综上所述，DEHP 给药导致肝毒性，包括氧化应激损伤和 CYP450 系统紊乱，但这些改变可能通过 AHR-Nrf2 途径的串扰被 LYC 改善。
