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抗逆转录病毒药物利匹韦林对人体皮下脂肪细胞的影响及其使用槲皮素的营养管理。

Effect of the anti-retroviral drug, rilpivirine, on human subcutaneous adipose cells and its nutritional management using quercetin.

机构信息

School of Forensic and Applied Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, England, UK.

Department of Pharmacology, United Arab Emirates University, Al Ain, United Arab Emirates.

出版信息

Mol Cell Biochem. 2020 Aug;471(1-2):1-13. doi: 10.1007/s11010-020-03744-4. Epub 2020 Jun 13.

Abstract

Rilpivirine, a recently developed drug of choice for initial treatment of HIV-1 infection, can greatly reduce HIV-related inflammation, but in turn, may be associated with adverse secondary effects, including disturbances in lipid metabolism and ultimately in adipose tissue distribution and function. In recent years, research findings on the benefits of anti-oxidant foods and supplements have been employed in counter-acting both oxidative stress as well as inflammation in order to reduce the adverse side effects of anti-retroviral therapy. One such natural flavonoid which possesses anti-inflammatory and anti-oxidative properties is quercetin. This study investigated the effect of quercetin in overcoming the side effects incurred due to rilpivirine administration. The results show substantial reduction in the accumulation of triglyceride levels in a dose- and time-dependent manner for adipose cells treated with either rilpivirine or quercetin alone and in combination, as evidenced by morphological pictures and quantitative measurement of triglycerides throughout the differentiation process. Levels of inflammatory markers such as resistin and IL-8 were increased as compared to the untreated cells. No significant changes in leptin were observed on treatment of adipose cells with rilpivirine alone and its levels were almost comparable to control. Levels of oxidative markers like superoxide dismutase, catalase, and glutathione were also decreased. Treatment with quercetin showed a decrease in the inflammatory status and an increase in the oxidative status of adipose cells, thereby exhibiting its anti-inflammatory and anti-oxidative properties. However, further assessment of lipid metabolism and adipose tissue function in patients administered with rilpivirine-based regimes is advisable considering that totally neutral effects of rilpivirine on lipid homeostasis cannot be anticipated from the current study in vitro. It is concluded that rilpivirine causes an anti-adipogenic and pro-inflammatory response pattern but only at high concentrations, whereas quercetin has been observed to decrease inflammation and restore the levels of anti-oxidant enzymes.

摘要

利匹韦林是一种最近开发的用于治疗 HIV-1 感染的首选药物,它可以大大降低 HIV 相关的炎症,但反过来,也可能与不良的次要效应相关,包括脂质代谢紊乱,最终导致脂肪组织分布和功能的改变。近年来,人们研究发现抗氧化食品和补充剂具有抗炎和抗氧化作用,可以对抗氧化应激和炎症,以减少抗逆转录病毒治疗的不良反应。一种具有抗炎和抗氧化特性的天然类黄酮是槲皮素。本研究探讨了槲皮素克服利匹韦林给药引起的副作用的效果。结果表明,在用利匹韦林或槲皮素单独或联合处理的脂肪细胞中,三酰甘油水平的积累呈剂量和时间依赖性显著减少,这从形态学图片和整个分化过程中三酰甘油的定量测量中可以得到证明。与未处理的细胞相比,抗炎标志物如抵抗素和 IL-8 的水平升高。单独用利匹韦林处理脂肪细胞时,瘦素没有明显变化,其水平与对照几乎相当。氧化标志物如超氧化物歧化酶、过氧化氢酶和谷胱甘肽的水平也降低。用槲皮素处理可降低脂肪细胞的炎症状态,增加其氧化状态,从而表现出其抗炎和抗氧化特性。然而,鉴于目前的体外研究不能预测利匹韦林对脂质平衡的完全中性影响,建议对接受基于利匹韦林的治疗方案的患者进行脂质代谢和脂肪组织功能的进一步评估。研究结果表明,利匹韦林引起抗脂肪生成和促炎反应模式,但仅在高浓度时,而槲皮素已被观察到可降低炎症并恢复抗氧化酶的水平。

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