Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
Inflammopharmacology. 2010 Oct;18(5):241-51. doi: 10.1007/s10787-010-0048-2. Epub 2010 Jul 3.
Chronic fatigue is an illness characterised by persistent and relapsing fatigue, often accompanied by numerous neuropsychiatric problems, such as anxiety and depression. The aetiology of chronic fatigue remains unclear so far. However, recent studies suggested the involvement of oxidative stress in this chronic debilitating disease. Alternatively, antioxidants have also been reported to have beneficial effect against chronic fatigue-like conditions. Therefore, present study has been designed to explore the potential role of pioglitazone, caffeic acid and their combination against chronic fatigue-like condition in mice. In the experimental protocol, the mice were put on the running wheel apparatus for 6 min test session daily for 21 days which produced fatigue-like condition. The locomotor activity and anxiety levels were measured on 0, 8th, 15th and 22nd days. The brains were isolated on 22nd day immediately after the behavioural assessments, oxidative damage and mitochondrial enzyme complexes were then estimated subsequently. Three weeks pioglitazone (5 and 10 mg/kg) and caffeic acid (5 and 10 mg/kg) pretreatment significantly attenuated the chronic fatigue-like condition (restored running wheel activity, locomotor activity and reduced anxiety-like behaviour) as compared to that in control (chronic fatigue) animals. Further, pioglitazone (5 and 10 mg/kg) and caffeic acid (5 and 10 mg/kg) drug treatments for 3 weeks significantly attenuated oxidative damage (decreased lipid peroxidation, nitrite concentration, restored reduction in glutathione and catalase levels), altered mitochondrial enzymes complex (I, II and IV) activities and mitochondrial redox activity (MTT assay) when compared with control. Further, combination of lower dose of pioglitazone (5 mg/kg) and caffeic acid (5 mg/kg) showed significant synergism in their protective effect which was significant as compared to their effect per se. The present study highlights the potential role of pioglitazone, caffeic acid and their combination in the pathophysiology of chronic fatigue-like condition in mice.
慢性疲劳是一种以持续性和复发性疲劳为特征的疾病，常伴有许多神经精神问题，如焦虑和抑郁。慢性疲劳的病因至今仍不清楚。然而，最近的研究表明，氧化应激参与了这种慢性衰弱性疾病。或者，抗氧化剂也被报道对慢性疲劳样病症有有益的作用。因此，本研究旨在探讨吡格列酮、咖啡酸及其组合对慢性疲劳样条件下小鼠的潜在作用。在实验方案中，将小鼠置于跑轮仪器上，每天进行 6 分钟的测试，持续 21 天，以产生疲劳样状态。在第 0、8、15 和 22 天测量运动活动和焦虑水平。在第 22 天的行为评估后立即分离大脑，随后评估氧化损伤和线粒体酶复合物。三周吡格列酮（5 和 10mg/kg）和咖啡酸（5 和 10mg/kg）预处理显著减轻了慢性疲劳样条件（恢复跑轮活动、运动活动和减少焦虑样行为），与对照（慢性疲劳）动物相比。此外，吡格列酮（5 和 10mg/kg）和咖啡酸（5 和 10mg/kg）药物治疗 3 周显著减轻氧化损伤（降低脂质过氧化、亚硝酸盐浓度，恢复谷胱甘肽和过氧化氢酶水平降低）、改变线粒体酶复合物（I、II 和 IV）活性和线粒体氧化还原活性（MTT 测定）与对照相比。此外，较低剂量的吡格列酮（5mg/kg）和咖啡酸（5mg/kg）联合使用显示出协同保护作用，与各自的作用相比，其协同作用更为显著。本研究强调了吡格列酮、咖啡酸及其组合在慢性疲劳样条件小鼠发病机制中的潜在作用。
