Original ContributionOxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms
Introduction
Chronic fatigue syndrome (CFS) is a condition characterised by debilitating fatigue and other nonspecific symptoms resulting in significant disability, and its pathophysiology continues to remain elusive. A number of biological systems have been implicated and there is mounting evidence that oxidative stress [1], [2], [3], [4], [5] and, more specifically, lipid peroxidation contribute to the disease process [6] and to some of the symptoms in the illness [1]. Oxidative stress has been defined as a disturbance to the equilibrium status of prooxidant and antioxidant systems in favour of prooxidation. The term oxidative stress is used to describe a number of chemical reactions involved in the production of free radicals and other reactive molecules that are potentially able to induce cellular injury.
While free radicals may generate tissue oxidative injury it is also evident that other oxidative by-products, especially peroxidised lipids such 8-iso-prostaglandin F2α, may be even more pivotal in the pathological process. 8-Iso-prostaglandin F2α is a member of the F2-isoprostane family and can exert potent biological activity, such as platelet activation, and act as a powerful vasoconstrictor of the peripheral vasculature [7], [8]. Such biological effects may be instrumental in the development of some of the vascular features that characterise patients with CFS [9], [10].
A further indication of the in vivo consequences of increased lipid peroxidation would be higher levels of oxidised low-density lipoproteins (oxLDL) accompanied by low levels of high-density lipoproteins (HDL), which are associated with the development of atherosclerosis [11]. This study set out to investigate, for the first time, levels of 8-iso-prostaglandin F2α alongside other markers of oxidative stress and antioxidant status in well-defined CFS patients and comparable control subjects, and to relate these levels to reported clinical symptoms of CFS.
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Subjects and methods
Fifty-four patients were recruited from a register of several hundred local CFS patients. After a medical examination 47 patients (19 males and 28 females, mean age 48 years [19–63 years], 6 current, 3 ex-, and 38 nonsmokers) were found to fulfil the Centres for Disease Control (CDC) classification for CFS [12]. Seven of the patients were excluded: one had diabetes, one had a possible neurological condition underlying the fatigue, one had angina, two patients were unable to undertake the tests,
Results
CFS patients in group 1 (CVD risk factor group) [n = 16; 5 males and 11 females, mean age 52.4 years (35–62 years)] were obese (BMI >30) and hypertensive, as defined by the European Society of Hypertension [systolic >140 mm Hg, or diastolic >90 mm Hg] [15]. CFS patients in group 2 [n = 31; 14 males and 17 females, mean age 46 years (19–64 years)] were normotensive and had a BMI of <30. Each patient group was compared with sex- and age-matched controls. Four of the controls had hypertension and
Discussion
The novel findings of this study are that patients with CFS have significantly elevated levels of F2-isoprostanes alongside other key markers of oxidative stress, and that these correlate with various CFS symptoms.
This is the first time that elevated levels of isoprostanes have been reported in patients with CFS and the finding is particularly important given their sensitivity, reliability, and association with other measures of lipid peroxidation in vivo [17], [18]. F2-isoprostanes are a
Acknowledgments
This study was supported by a grant from MERGE (Myalgic Encephalomyelitis Research Group for Education and Support, registered UK charity number 1080201), Perth PH1 5PP, Scotland, UK. J.J.F.B and M.McL receive funding from the Sir John Fisher Foundation.
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