Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University for sustainable development, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
Biomed Pharmacother. 2022 Sep;153:113526. doi: 10.1016/j.biopha.2022.113526. Epub 2022 Aug 12.
The prevalence of metabolic syndrome (MetS) has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care system. MetS is generally linked to complications in lipid metabolism, oxidative stress and low grade inflammation. The aim of the current study was to evaluate the effect of rosuvastatin, co-enzyme Q10 (CoQ10), and their combination on blood pressure, blood sugar, dyslipidemia, and liver function in rats with MetS induced by high fructose and high fat diet (HF-HFD) and the possible underlying mechanism. Oral administration of rosuvastatin (10 mg/kg/day), CoQ10 (10 mg/kg/day) and their combination for 4 weeks in HF-HFD-fed rats elevated serum high density lipoprotein and reduced glutathione. On the other hand, treatment with rosuvastatin, CoQ10 or their combination decreased the serum levels of malondialdehyde, triglycerides, total cholesterol, and low density lipoprotein-cholesterol as well as systolic blood pressure, body weight and fasting blood glucose level. In addition, the drugs or their combination declined serum pro-inflammatory cytokines, namely tumor necrosis factor-α and interleukin-1β. In conclusion, our results showed that rosuvastatin or CoQ10 protected against HF-HFD-induced MetS through the regulation of dyslipidemia, elevated blood glucose, elevated blood pressure, antioxidant defenses and inflammatory response. Rosuvastatin or CoQ10 also alleviated the impairment of liver function that was induced by HF-HFD. Interestingly, CoQ10 augmented rosuvastatin's effect in ameliorating MetS, via exerting synergistic modulatory effects on oxidative stress and inflammation. Thus, rosuvastatin and CoQ10 combination therapy may have possible applications in ameliorating metabolic disorders.
代谢综合征(MetS)的患病率呈惊人上升趋势,现已成为全球关注的问题,给医疗保健系统带来了巨大的经济负担。MetS 通常与脂质代谢、氧化应激和低度炎症有关。本研究旨在评估瑞舒伐他汀、辅酶 Q10(CoQ10)及其联合用药对高果糖高脂肪饮食(HF-HFD)诱导的 MetS 大鼠血压、血糖、血脂异常和肝功能的影响,并探讨其可能的作用机制。在 HF-HFD 喂养的大鼠中,连续 4 周口服瑞舒伐他汀(10mg/kg/天)、CoQ10(10mg/kg/天)及其联合用药可升高血清高密度脂蛋白和还原型谷胱甘肽。另一方面,瑞舒伐他汀、CoQ10 或两者联合治疗可降低血清丙二醛、甘油三酯、总胆固醇和低密度脂蛋白胆固醇以及收缩压、体重和空腹血糖水平。此外,这些药物或其联合用药还降低了血清促炎细胞因子,即肿瘤坏死因子-α和白细胞介素-1β的水平。总之,我们的研究结果表明,瑞舒伐他汀或 CoQ10 通过调节血脂异常、升高血糖、升高血压、抗氧化防御和炎症反应,对 HF-HFD 诱导的 MetS 具有保护作用。瑞舒伐他汀或 CoQ10 还减轻了 HF-HFD 引起的肝功能损害。有趣的是,CoQ10 通过对氧化应激和炎症产生协同调节作用,增强了瑞舒伐他汀改善 MetS 的作用。因此,瑞舒伐他汀和 CoQ10 的联合治疗可能在改善代谢紊乱方面具有潜在的应用价值。