Oxidative stress and fatigue in systemic lupus erythematosus

Abstract

Objective: The objective of this study is to investigate the relationship of oxidative stress to fatigue in systemic lupus erythematosus (SLE). Methods: Patients with a confirmed diagnosis of SLE by ACR criteria and healthy controls completed validated questionnaires to assess depression and fatigue. Fatigue was measured with the Fatigue Severity Scale (FSS) and the Profile of Fatigue (Prof-F). Visual analogue scales (VAS) were also used to assess fatigue and pain. Depression was measured with the Center for Epidemiologic Studies Depression Scale (CES-D). Plasma F2-isoprostane was measured with gas chromatography/mass spectroscopy to assess oxidative stress. Evaluation included medical record review, physical exam and calculation of body mass index (BMI), disease activity (SLEDAI) and damage (SLICC) in the SLE patients. Results: Seventy-one SLE patients with low disease activity (mean SLEDAI = 1.62 standard error (SE) 0.37, range 0–8) were compared to 51 controls. Fatigue-limiting physical activity (defined as FSS ≥ 4) was present in 56% of patients and 12% of controls. F2-isoprostane was higher in SLE patients with fatigue compared to not-fatigued SLE subjects ( p = .0076) who were otherwise similar in ethnicity, disease activity and cardiovascular risk factors. Plasma F2-isoprostane was strongly correlated with FSS and Profile of Somatic Fatigue (Prof-S) ( p < .0001), VAS fatigue ( p = .005), CES-D ( p = .008) and with BMI ( p = .0001.) In a multivariate model, F2-isoprostane was a significant predictor of FSS after adjustment for age, BMI, pain and depression ( p = .0002). Conclusion: Fatigue in SLE patients with low disease activity is associated with increased F2-isoprostane. F2-isoprostane could provide a useful biomarker to explore mitochondrial function and the regulation of oxidative pathways in patients with SLE in whom fatigue is a debilitating symptom.

Association of mitochondrial dysfunction and fatigue: A review of the literature

“…A positive correlation between F 2 -isoprostane and fatigue was observed in SLE patients and it was observed that F 2 -isoprostane predicts higher FSS scores in SLE patients. F 2 -isoprostane is currently acknowledged as the most reliable measure of in vivo oxidative stress [36]. The results from this study provide further evidence of an association between oxidative stress and the development of fatigue.…”

“…They observed that fatigued SLE patients had higher levels of F 2 -isoprostane than non-fatigued SLE patients [36]. A positive correlation between F 2 -isoprostane and fatigue was observed in SLE patients and it was observed that F 2 -isoprostane predicts higher FSS scores in SLE patients.…”

“…Impaired oxidative phosphorylation was noted through reduced citrate synthase activity [24], [37]. Electron transport chain activity was disrupted as evidenced by reduced levels of succinate reductase (Complex I), cytochrome-c oxidase (Complex IV), and CoQ10 (electron shuttle from Complex I and II to Complex III), as well as evidenced through disrupted oxidative stress (decreased levels of antioxidants and increased levels of ROS and F 2 -isoprostance) [19], [20], [22], [23], [24], [36]. ATP concentration, recycling, and the efficiency of oxidative phosphorylation were found to be disrupted through the ATP Profile Test [5], [25].…”

Oxidative stress and its biomarkers in systemic lupus erythematosus

“…Levels of F2-Isoprostanes in plasma and urine samples have been shown to correlate with in vivo oxidative stress in a number of studies in SLE patients. Studies from Avalos (95 SLE patients), Segal group (71 SLE patients) and Abou-Raya (60 SLE patients) have shown that F2 isoprostane levels are associated with increased disease activity, fatigue and lower quality of life [31,33,91]. …”

Показники Прооксидантно-Антиоксидантної Системи Печінки При Експериментальному Антифосфоліпідному Синдромі Та Застосуванні L-Аргініну

“…Порушення балансу між концентрацією активних форм кисню (АФК) і компонентів антиоксидант-ної системи (АОС) призводить до оксидативно-го стресу, окисного пошкодження ДНК, білків та ліпідів [29]. Помірне зростання рівня АФК активує ферментативну ланку АОС.…”