oxidative stress – Page 9 – American ME and CFS Society

Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

BACKGROUND: There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress.

MATERIAL/METHODS: Blood was collected from 56 patients with ME/CFS and 37 normal volunteers. Severity of ME/CFS was measured using the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: Plasma peroxide concentrations were significantly higher in patients with ME/CFS than in normal controls. There was a trend towards significantly higher serum oxLDL antibodies in ME/CFS than in controls. Both biomarkers contributed significantly in discriminating between patients with ME/CFS and normal controls. Plasma peroxide and serum oxLDL antibody levels were both significantly related to one of the FF symptoms.

CONCLUSIONS: The results show that ME/CFS is characterized by increased oxidative stress.

Source: Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monit. 2011 Apr;17(4):SC11-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539515/ (Full article)

Lipid peroxidation is elevated in female patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome is a debilitating disease of unclear cause and pathogenesis. It affects mostly women from lower socioeconomic classes. There is mounting evidence that oxidative stress, specifically lipid peroxidation (LPO) contributes to the disease process. We investigated levels of LPO and its possible consequences for these patients.

MATERIAL/METHODS: Forty women aged 15-45 years who fulfilled the 1994 Centers for Disease Control’s diagnostic criteria for chronic fatigue syndrome (CFS) with no comorbidities were recruited and were age matched to a control group of 40 healthy women. Levels of total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDLc), HDL cholesterol (HDLc), and malondialdehyde (MDA) levels were measured.

RESULTS: Although initial statistical analyses showed no differences between groups (P=.345), when subdivided according to the level of MDA, a difference was found in the subgroup of high-level MDA (P=.034). There was a negative correlation between HDLc and MDA levels (r=0.3; P=.046), a positive correlation between TG and MDA levels (r=0.4; P=.006), and lower levels of HDL cholesterol in the CFS group (P=.036).

CONCLUSIONS: High levels of MDA, positively correlated with TG and lower HDL levels, might be indicative of proatherogenic events in female CFS patients, a group not otherwise considered a risk for atherosclerosis.

Source: Brkic S, Tomic S, Maric D, Novakov Mikic A, Turkulov V. Lipid peroxidation is elevated in female patients with chronic fatigue syndrome. Med Sci Monit. 2010 Dec;16(12):CR628-32. https://www.ncbi.nlm.nih.gov/pubmed/21119582

Biochemical and vascular aspects of pediatric chronic fatigue syndrome

Abstract:

OBJECTIVE: To evaluate the biochemical and vascular aspects of pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

DESIGN: Cross-sectional clinical study.

SETTING: Tayside, Scotland, United Kingdom.

PARTICIPANTS: Twenty-five children with CFS/ME and 23 healthy children recruited from throughout the United Kingdom.

INTERVENTIONS: Participants underwent a full clinical examination to establish a diagnosis of CFS/ME and were asked to describe and score their CFS/ME symptoms. Biochemical markers were measured. Arterial wave reflection was estimated to assess systemic arterial stiffness.

MAIN OUTCOME MEASURES: Markers of oxidative stress and free radicals, C-reactive protein level, white blood cell apoptosis, and arterial wave reflection.

RESULTS: Children with CFS/ME had increased oxidative stress compared with control individuals (isoprostanes: 252.30 vs 215.60 pg/mL, P = .007; vitamin C, mean [SD]: 0.84 [0.26] vs 1.15 [0.28] mg/dL, P < .001; vitamin E, 8.72 [2.39] vs 10.94 [3.46] microg/mL, P = .01) and increased white blood cell apoptosis (neutrophils: 53.7% vs 35.7%, P = .005; lymphocytes: 40.1% vs 24.6%, P = .009). Arterial stiffness variables did not differ significantly between groups (mean augmentation index, -0.57% vs -0.47%, P = .09); however, the derived variables significantly correlated with total (r = 0.543, P = .02) and low-density lipoprotein (r = 0.631, P = .004) cholesterol in patients with CFS/ME but not in controls.

CONCLUSIONS: Biomedical anomalies seen in adults with CFS/ME-increased oxidative stress and increased white blood cell apoptosis-can also be observed in children with clinically diagnosed CFS/ME compared with matched controls. Unlike in their adult counterparts, however, arterial stiffness remained within the reference range in these pediatric patients.

Comment in: Chronic fatigue syndrome in adolescence: where to from here? [Arch Pediatr Adolesc Med. 2010]

Source: Kennedy G, Khan F, Hill A, Underwood C, Belch JJ. Biochemical and vascular aspects of pediatric chronic fatigue syndrome. Arch Pediatr Adolesc Med. 2010 Sep;164(9):817-23. doi: 10.1001/archpediatrics.2010.157. https://www.ncbi.nlm.nih.gov/pubmed/20819963

Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome

Abstract:

The etiology of chronic fatigue syndrome remains unknown. Oxidative stress may be involved in its pathogenesis. Vitamin E is a major endogenous lipid-soluble antioxidative substance, and is consumed during the lipid peroxidation process.

We studied a population comprising 27 patients with chronic fatigue syndrome (10 men and 17 women, 29 +/- 6 years of age) and 27 age- and sex-matched control subjects. Serum vitamin E (alpha-tocopherol) concentrations were determined and expressed as mg/g total lipids (total cholesterol and triglyceride) to evaluate oxidative stress. Serum alpha-tocopherol concentrations (mg/g lipids) were significantly (P < 0.001) lower in the patients with chronic fatigue syndrome (2.81 +/- 0.73) than in the control subjects (3.88 +/- 0.65).

The patients with chronic fatigue syndrome were re-examined during a follow-up interval. After 8 +/- 2 months, 16 patients exhibited a status that warranted re-examination during remission of the symptoms at a regular visit to our hospital (Group 1), while the remaining 11 did not (Group 2). The serum alpha-tocopherol levels were significantly elevated during remission as compared with those at baseline in Group 1 (2.71 +/- 0.62 –> 3.24 +/- 0.83, P < 0.001). The levels did not significantly change after the interval in Group 2 (2.97 +/- 0.86 –> 2.85 +/- 0.73, not significant).

In conclusion, serum alpha-tocopherol concentrations were significantly lower in the patients with chronic fatigue syndrome as compared with the control subjects, suggesting increased oxidative stress in the former. The low level of serum alpha-tocopherol was ameliorated during the remission phase as compared with the exacerbation phase in the patients with chronic fatigue syndrome, suggesting that increased oxidative stress may be involved in the pathogenesis of chronic fatigue syndrome and might also be directly related to the severity of the symptoms of chronic fatigue syndrome.

Source: Miwa K, Fujita M. Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels. 2010 Jul;25(4):319-23. doi: 10.1007/s00380-009-1206-6. Epub 2010 Jul 31. https://www.ncbi.nlm.nih.gov/pubmed/20676841

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways

Abstract:

There is a significant ‘comorbidity’ between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy.

This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2′-5′ oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS.

Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways.

Depression and ME/CFS are not ‘comorbid’ disorders, but should be regarded as ‘co-associated disorders’ that are clinical manifestations of shared pathways.

Source: Maes M. An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):784-94. doi: 10.1016/j.pnpbp.2010.06.023. Epub 2010 Jul 4. https://www.ncbi.nlm.nih.gov/pubmed/20609377

Possible role of oxidative stress and immunological activation in mouse model of chronic fatigue syndrome and its attenuation by olive extract

Abstract:

Various putative theories involved in the development of chronic fatigue syndrome revolve around the role of stress, infection and oxidative stress. Scientific evidence highlighting the protective role of nutritional supplements in chronic fatigue syndrome is lacking.

Based on these assumptions, the present study was designed to evaluate the effect of olive extract in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigen were used as immunogens. The assessment of chronic fatigue syndrome was based on immobility period during chronic water-immersion stress test for 10 min daily. The stress-induced hyperalgesia was measured by tail withdrawal latency.

Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and oxidative stress on the 19th day. Serum tumor necrosis factor-alpha (TNF-α) levels were also markedly increased with LPS or BA challenge.

Concurrent treatment with olive extract resulted in a significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as serum TNF-α levels. The results of the present study strongly indicate the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome and highlight the valuable role of olive extract in combating chronic fatigue syndrome.

Source: Gupta A, Vij G, Chopra K. Possible role of oxidative stress and immunological activation in mouse model of chronic fatigue syndrome and its attenuation by olive extract. J Neuroimmunol. 2010 Sep 14;226(1-2):3-7. doi: 10.1016/j.jneuroim.2010.05.021. Epub 2010 May 26. https://www.ncbi.nlm.nih.gov/pubmed/20537729

Modulation of antigen-induced chronic fatigue in mouse model of water immersion stress by naringin, a polyphenolic antioxidant

Abstract:

It is believed that physical stress, infection and oxidative stress are involved in the development of chronic fatigue syndrome. There is little evidence stating the beneficial role of nutritional supplements in chronic fatigue syndrome. Based on this, this study was designed to evaluate the effect of naringin, a natural polyphenol, in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) as well as Brucella abortus (BA) antigen was used as immunogens.

The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 mins as well as measurement of hyperalgesia for 19 days. Immobility time and tail withdrawal latency as well as oxidative stress were taken as the markers of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and oxidative stress on 19th day. Serum tumor necrosis factor-alpha (TNF-alpha) levels markedly increased with LPS or BA challenge.

Concurrent treatment with naringin resulted in the significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as in TNF-alpha levels. Present findings strongly suggest the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome, and treatment with naringin can be a valuable option in chronic fatigue syndrome.

Source: Vij G, Gupta A, Chopra K. Modulation of antigen-induced chronic fatigue in mouse model of water immersion stress by naringin, a polyphenolic antioxidant. Fundam Clin Pharmacol. 2009 Jun;23(3):331-7. doi: 10.1111/j.1472-8206.2009.00675.x. Epub 2009 Mar 11. https://www.ncbi.nlm.nih.gov/pubmed/19469804

Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses

Abstract:

OBJECTIVES: As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic fatigue syndrome (CFS) who present an accentuated exercise-induced oxidative stress.

DESIGN: This case-control study compared nine CFS patients to a gender-, age- and weight-matched control group of nine healthy sedentary subjects.

INTERVENTIONS: All subjects performed an incremental cycling exercise continued until exhaustion. We measured ventilation and respiratory gas exchange and evoked compound muscle potential (M-wave) recorded from vastus lateralis. Repetitive venous blood sampling allowed measurements of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)], two cytokines (IL-6 and TNF-alpha) and two Hsp (Hsp27 and Hsp70) at rest, during maximal exercise and the 60-min recovery period.

RESULTS: Compared with controls, resting CFS patients had low baseline levels of RAA and Hsp70. Their response to maximal exercise associated (i) M-wave alterations indicating reduced muscle membrane excitability, (ii) early and accentuated TBARS increase accompanying reduced changes in RAA level, (iii) absence of significant increase in IL-6 and TNF-alpha, and (iv) delayed and marked reduction of Hsp27 and Hsp70 variations. The post-exercise increase in TBARS was accentuated in individuals having the lowest variations of Hsp27 and Hsp70.

CONCLUSIONS: The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress, which might result from delayed and insufficient Hsp production.

Source: Jammes Y, Steinberg JG, Delliaux S, Brégeon F.Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med. 2009 Aug;266(2):196-206. doi: 10.1111/j.1365-2796.2009.02079.x. Epub 2009 May 19. https://www.ncbi.nlm.nih.gov/pubmed/19457057

Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome

Abstract:

The aim of the current study was to investigate the levels of interleukin-6 (IL-6), its soluble receptors (sIL-6R and sgp130) and F(2)-isoprostanes, at rest and during exercise, in patients with chronic fatigue syndrome (CFS).

Six male CFS patients and six healthy controls performed an incremental exercise test to exhaustion and a submaximal exercise bout to exhaustion. Blood samples taken in the submaximal test at rest, immediately post-exercise and 24 h post-exercise were analyzed for IL-6, sIL-6R, sgp130 and F(2)-isoprostanes. A further 33 CFS and 33 healthy control participants gave a resting blood sample for IL-6 and sIL-6R measurement.

During the incremental exercise test only power output at the lactate threshold was lower (P<0.05) in the CFS group. F(2)-isoprostanes were higher (P<0.05) in CFS patients at rest and this difference persisted immediately and 24 h post-exercise. The exercise study found no differences in IL-6, sIL-6R or sgp130 at any time point between groups. In the larger resting group, there were no differences in IL-6 and sIL-6R between CFS and control groups. This investigation has demonstrated that patients with CFS do not have altered plasma levels of IL-6, sIL-6R or sgp130 either at rest or following exercise. F(2)-isoprostanes, however, were consistently higher in CFS patients.

Source: Robinson M, Gray SR, Watson MS, Kennedy G, Hill A, Belch JJ, Nimmo MA. Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome. Scand J Med Sci Sports. 2010 Apr;20(2):282-90. doi: 10.1111/j.1600-0838.2009.00895.x. Epub 2009 Apr 13. https://www.ncbi.nlm.nih.gov/pubmed/19422646

The role of antioxidant properties of Nardostachys jatamansi in alleviation of the symptoms of the chronic fatigue syndrome

Abstract:

An experimental model of chronic fatigue syndrome (CFS) is utilized for evaluation of antidepressant, anti-stress effects, wherein the rat is forced to swim in water for 15 min/day on 21 consecutive days. Rats were divided into stressed control, stressed plus standard drug (Panax ginseng) and stressed plus 200 and 500 mg/kg of test drug, i.e., Nardostachys jatamansi extract (NJE) given orally.

The immobility during each 5 min periods of 0-5, 5-10 and 10-15 min of stress were noted. Similarly the climbing (struggling) behaviour was noted in the above four groups of rats in intervals of 5 min. The locomotor activity and also the anxiety state in animals were evaluated in an elevated plus maze after CFS in all the four groups. There was a significant increase in despair behaviour and anxiety in stressed control animals on successive days of CFS. Locomotor activity gradually decreased in stressed control group. Treatment with NJE (200 and 500 mg/kg) significantly reversed both paradigms.

Biochemical analysis showed that CFS significantly increased lipid peroxidation, nitrite and superoxide dismutase levels and decreased catalase level in rat brain. Administration of NJE (200 and 500 mg/kg) tended to normalize both augmented lipid peroxidation, nitrite, superoxide dismutase activities and catalase level significantly. NJE per se has an antioxidant effect. The results indicate that CFS may lead to oxidative stress, which is mitigated by NJE and so its antioxidant property may be responsible for anti-stress effect of NJE.

Source: Lyle N, Gomes A, Sur T, Munshi S, Paul S, Chatterjee S, Bhattacharyya D. The role of antioxidant properties of Nardostachys jatamansi in alleviation of the symptoms of the chronic fatigue syndrome. Behav Brain Res. 2009 Sep 14;202(2):285-90. doi: 10.1016/j.bbr.2009.04.005. Epub 2009 Apr 16. https://www.ncbi.nlm.nih.gov/pubmed/19375459