Research Unit of Macromolecular Biochemistry and Genetics, Faculty of Sciences of Gafsa, 2112, Gafsa, Tunisia.
Laboratoire des Sciences de l'Environnement, Biologie et Physiologie des Organismes Aquatiques, LR18ES41, Faculté des Sciences de Tunis, Université Tunis EL Manar, 2092, Tunis, Tunisia.
Ecotoxicol Environ Saf. 2020 Apr 15;193:110318. doi: 10.1016/j.ecoenv.2020.110318. Epub 2020 Feb 24.
The current study aimed to examine, for the first time, the relationship between exposure to deltamethrin (DLM) and atherogenic lipid profile disorders in adult Wistar rats, as well as, to verify the mechanism of the beneficial role of Zygophyllum album leaves extracts (ZALE). The experimental study was assessed using DLM (4 mg/kg b.w) either alone or co administered with ZALE (400 mg/kg b.w) orally for 90 days in rats. RP-HPLC-DAD-ESI-QTOF-MS was used to identify the bioactive metabolites present in ZALE. Plasmatic and aortic total cholesterol (TC), LDL-cholesterol (LDL-C), native LDL (LDL-apo B-100) and oxidized LDL (ox-LDL) were evaluated using auto-analyzer and a sandwich ELISA, respectively. The protein expressions of LDLR (native LDL receptor) and CD36 (Scavenger receptor class B) were evaluated in aorta or liver with a Western blot. The pathology has been confirmed with lipid stain (Oil Red O). Phytochemicals analysis revealed the presence of fifteen saponins in ZALE. Rats intoxicated with DLM revealed a significant increase in plasmatic and aortic lipid profile (TC, LDL-C, LDL-apo B-100 and ox-LDL), as well as, the concentration of the plasmatic cytokines include TNF-α, IL-2 and IL-6, compared to control. Hepatic native LDL and aortic CD36 receptor expression were increased in DLM treated group, however aortic LDL-R does not present any modification, when compared to control. The detected disturbances in lipid parameters were supported by Oil Red O applied. Due to their antioxidant activity, the bioactive compounds in ZALE as powerful agents able to prevent the pro-atherogenic effect observed in DLM-treated animals. These metabolites modulated most of inflammatory markers, prevented accumulation of lipid and lipoprotein biomarkers, regulated the major receptor regulators of hepatic cholesterol metabolism, as well as normalize lipid distribution in liver and aorta tissue.
本研究首次旨在探讨，除虫菊酯（DLM）暴露与成年 Wistar 大鼠动脉粥样硬化脂质谱紊乱之间的关系，并验证骆驼蓬叶提取物（ZALE）的有益作用机制。使用 DLM（4mg/kg b.w）进行实验研究，要么单独使用，要么与 ZALE（400mg/kg b.w）一起口服给药 90 天。RP-HPLC-DAD-ESI-QTOF-MS 用于鉴定 ZALE 中存在的生物活性代谢物。使用自动分析仪和夹心 ELISA 分别评估血浆和主动脉总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、天然 LDL（LDL-apoB-100）和氧化 LDL（ox-LDL）。使用 Western blot 评估 LDLR（天然 LDL 受体）和 CD36（清道夫受体 B 类）在主动脉或肝脏中的蛋白表达。病理学已通过脂质染色（油红 O）确认。植物化学分析显示 ZALE 中存在十五种皂苷。与对照组相比，DLM 中毒的大鼠显示血浆和主动脉脂质谱（TC、LDL-C、LDL-apoB-100 和 ox-LDL）以及包括 TNF-α、IL-2 和 IL-6 在内的血浆细胞因子浓度显著增加。与对照组相比，DLM 处理组中肝内天然 LDL 和主动脉 CD36 受体表达增加，但主动脉 LDL-R 没有任何变化。脂质参数的检测到的紊乱得到了应用的油红 O 的支持。由于其抗氧化活性，ZALE 中的生物活性化合物作为能够预防 DLM 处理动物中观察到的促动脉粥样硬化作用的有效药物。这些代谢物调节了大多数炎症标志物，防止脂质和脂蛋白生物标志物的积累，调节肝胆固醇代谢的主要受体调节剂，并使脂质在肝脏和主动脉组织中的分布正常化。
