Boots Agnes W, Drent Marjolein, Swennen Els L R, Moonen Harald J J, Bast Aalt, Haenen Guido R M M
Department of Pharmacology and Toxicology, Maastricht University, The Netherlands.
Respir Med. 2009 Mar;103(3):364-72. doi: 10.1016/j.rmed.2008.10.007. Epub 2008 Nov 17.
Enhanced production of reactive oxygen species (ROS), capable of reducing endogenous defense levels and enhancing inflammation, is suggested to play a role in sarcoidosis. Antioxidant supplementation might offer protection against such ROS-mediated damage. A promising candidate for antioxidant supplementation is the flavonoid quercetin.
To determine the antioxidant and inflammatory status in sarcoidosis. Furthermore, the potential of quercetin to mitigate the occurring inflammation will be assessed.
Non-smoking sarcoidosis patients and healthy controls matched for age, gender and dietary behavior were enrolled (NCT-00512967). Measurements included assessment of total plasma antioxidant capacity, vitamin C, uric acid, glutathione, basal and LPS-induced levels of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-8 and -10 as well as the effect of quercetin on these levels.
Compared to their controls, the sarcoidosis patients displayed significantly lower total plasma antioxidant capacity, decreased levels of vitamin C, uric acid and glutathione and increased levels of basal TNFalpha and IL-8. Quercetin significantly decreased ex vivo LPS-induced TNFalpha- and IL-8 production in a concentration-dependent manner in both groups. Interestingly, this quercetin effect was more pronounced in sarcoidosis patients.
The endogenous antioxidant defense was significantly reduced in sarcoidosis, indicating that oxidative stress underlies the pathology of this disease. Furthermore, the inflammatory status was significantly enhanced in sarcoidosis. Finally, our results regarding the effect of quercetin on cytokine production imply that sarcoidosis patients might benefit from antioxidant supplementation not only by empowering the relatively low protection against ROS but also by reducing inflammation.
活性氧（ROS）生成增加被认为在结节病中起作用，ROS能够降低内源性防御水平并加剧炎症。补充抗氧化剂可能提供针对此类ROS介导损伤的保护作用。黄酮类化合物槲皮素是补充抗氧化剂的一个有前景的候选物。
确定结节病患者的抗氧化和炎症状态。此外，评估槲皮素减轻炎症的潜力。
纳入年龄、性别和饮食行为相匹配的非吸烟结节病患者和健康对照（NCT-00512967）。测量包括评估血浆总抗氧化能力、维生素C、尿酸、谷胱甘肽、基础及脂多糖（LPS）诱导的肿瘤坏死因子α（TNFα）、白细胞介素（IL）-8和-10水平，以及槲皮素对这些水平的影响。
与对照组相比，结节病患者的血浆总抗氧化能力显著降低，维生素C、尿酸和谷胱甘肽水平下降，基础TNFα和IL-8水平升高。槲皮素在两组中均以浓度依赖的方式显著降低体外LPS诱导的TNFα和IL-8生成。有趣的是，这种槲皮素效应在结节病患者中更为明显。
结节病患者的内源性抗氧化防御显著降低，表明氧化应激是该疾病病理的基础。此外，结节病患者的炎症状态显著增强。最后，我们关于槲皮素对细胞因子生成影响的结果表明，结节病患者可能不仅通过增强对ROS相对较低的保护，还通过减轻炎症而从补充抗氧化剂中获益。
