Othman Zaidatul Akmal, Zakaria Zaida, Suleiman Joseph Bagi, Ghazali Wan Syaheedah Wan, Mohamed Mahaneem
Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kelantan, Malaysia.
Unit of Physiology, Universiti Sultan Zainal Abidin, Kuala Terengganu, 20400 Terengganu, Malaysia.
Antioxidants (Basel). 2021 Feb 6;10(2):251. doi: 10.3390/antiox10020251.
Obesity is typically linked to oxidative stress and inflammation, which lead to vascular damage and initiate the progression of atherosclerosis. The aim of this study was to determine the anti-atherosclerotic effect of orlistat on obesity-induced vascular oxidative stress in obese male rats. Twenty-four male Sprague-Dawley rats were categorized into two groups: normal (Normal group, = 6) and high-fat diet (HFD group, = 12). After six weeks, obese rats in the HFD group were administered either with distilled water (OB group) or orlistat 10 mg/kg/day (OB/OR group) for another six weeks. The OB group had a significant increase in lipid profiles (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)) and decrease in high-density lipoprotein (HDL) level compared to the Normal group. The aortic antioxidants enzymes activities (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and catalase (CAT)) as well as total glutathione (GSH) and total antioxidant capacity (TAC) of the OB group were significantly decreased compared to the Normal group. Furthermore, pro-inflammatory atherosclerotic markers (tumour necrosis factor-alpha (TNF-ɑ), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1)) expressions were increased significantly, and anti-inflammatory marker (interleukin-10 (IL-10)) was decreased significantly in the OB group compared to the Normal group. Treatment with orlistat significantly improved lipid profile, increased antioxidant enzymes and expression of anti-inflammatory markers, and decreased the expression of the pro-inflammatory marker compared to the OB group. These findings may suggest the therapeutic effect of orlistat in attenuating the progression of the atherosclerotic stage in obesity.
肥胖通常与氧化应激和炎症相关，这会导致血管损伤并引发动脉粥样硬化的进展。本研究的目的是确定奥利司他对肥胖雄性大鼠肥胖诱导的血管氧化应激的抗动脉粥样硬化作用。将24只雄性Sprague-Dawley大鼠分为两组：正常组（正常组，n = 6）和高脂饮食组（HFD组，n = 12）。六周后，HFD组中的肥胖大鼠再接受六周的蒸馏水（OB组）或10 mg/kg/天的奥利司他（OB/OR组）治疗。与正常组相比，OB组的血脂水平（总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL））显著升高，高密度脂蛋白（HDL）水平降低。与正常组相比，OB组的主动脉抗氧化酶活性（超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽还原酶（GR）、谷胱甘肽S-转移酶（GST）和过氧化氢酶（CAT））以及总谷胱甘肽（GSH）和总抗氧化能力（TAC）显著降低。此外，与正常组相比，OB组的促炎动脉粥样硬化标志物（肿瘤坏死因子-α（TNF-α）、血管细胞粘附分子-1（VCAM-1）和细胞间细胞粘附分子-1（ICAM-1））表达显著增加，抗炎标志物（白细胞介素-10（IL-10））显著降低。与OB组相比，奥利司他治疗显著改善了血脂水平，增加了抗氧化酶和抗炎标志物的表达，并降低了促炎标志物的表达。这些发现可能提示奥利司他在减轻肥胖中动脉粥样硬化阶段进展方面的治疗作用。
