Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, PR China.
Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, PR China.
Spectrochim Acta A Mol Biomol Spectrosc. 2019 Oct 5;221:117149. doi: 10.1016/j.saa.2019.117149. Epub 2019 May 22.
Bisphenol A (BPA) as a chemical raw material, is widely used in the manufacturing process of daily necessities. It was reported that BPA could induce oxidative stress, and catalase (CAT) can protect the body from oxidative stress. In this paper, the effect of BPA on CAT was carried out in vitro and in vivo. Firstly, we studied the effects of BPA on oxidative stress, cell viability and CAT activity in human hepatocytes, and the results of vitro experiments show that the survival rate of hepatocytes significant decreased along with the increase of BPA concentration. And when the BPA concentration was 100 μM, the hepatocyte survival decreased by 13.2%, ROS levels in the cells increased by 85%. However, the activity of intracellular CAT increased with the increasing concentration of BPA in 24 h. The results of vivo experiments showed that the activity of CAT in the high-dose group decreased by 29.1% compared with the control group. The long-term effects of BPA on rats reduced the CAT activity in liver, which reduced the resistance to oxidative stress. Meanwhile, the interaction mechanism between BPA and CAT at the molecule level was performed via multiple spectra methods and molecular docking, and the results illustrated that the structural change of CAT is mainly due to the strong combination of BPA with the residues of Trp185. In addition, the interaction mechanism between BPA and CAT were hydrophobic and electrostatic effect. This study provided experimental evidence for better understanding the toxicity of BPA.
双酚 A（BPA）作为一种化学原料，广泛应用于日用品的制造过程中。有报道称，BPA 可诱导氧化应激，而过氧化氢酶（CAT）可以保护身体免受氧化应激。本研究采用体外和体内实验方法探讨 BPA 对 CAT 的影响。首先，我们研究了 BPA 对人肝细胞氧化应激、细胞活力和 CAT 活性的影响，结果表明，随着 BPA 浓度的增加，肝细胞存活率显著降低。当 BPA 浓度为 100 μM 时，肝细胞存活率下降了 13.2%，细胞内 ROS 水平升高了 85%。然而，在 24 h 内，细胞内 CAT 的活性随着 BPA 浓度的增加而增加。体内实验结果表明，与对照组相比，高剂量组 CAT 活性下降了 29.1%。BPA 对大鼠的长期影响降低了肝脏中的 CAT 活性，降低了其抵抗氧化应激的能力。同时，采用多种光谱方法和分子对接技术研究了 BPA 与 CAT 之间的分子相互作用机制，结果表明 CAT 的结构变化主要是由于 BPA 与 Trp185 残基的强结合。此外，BPA 与 CAT 之间的相互作用机制为疏水作用和静电作用。本研究为更好地理解 BPA 的毒性提供了实验依据。
