Tag: reactive oxygen species

A Proposed New Model to Explain the Role of Low Dose Non-DNA Targeted Radiation Exposure in Chronic Fatigue and Immune Dysfunction Syndrome

Abstract:

Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) is considered to be a multidimensional illness whose etiology is unknown. However, reports from Chernobyl, as well as those from the United States, have revealed an association between radiation exposure and the development of CFIDS. As such, we present an expanded model using a systems biology approach to explain the etiology of CFIDS as it relates to this cohort of patients. This paper proposes an integrated model with ionizing radiation as a suggested trigger for CFIDS mediated through UVA induction and biophoton generation inside the body resulting from radiation-induced bystander effects (RIBE).
Evidence in support of this approach has been organized into a systems view linking CFIDS illness markers with the initiating events, in this case, low-dose radiation exposure. This results in the formation of reactive oxygen species (ROS) as well as important immunologic and other downstream effects. Furthermore, the model implicates melanoma and subsequent hematopoietic dysregulation in this underlying process. Through the identification of this association with melanoma, clinical medicine, including dermatology, hematology, and oncology, can now begin to apply its expansive knowledge base to provide new treatment options for an illness that has had few effective treatments.
Source: Cocchetto A, Seymour C, Mothersill C. A Proposed New Model to Explain the Role of Low Dose Non-DNA Targeted Radiation Exposure in Chronic Fatigue and Immune Dysfunction Syndrome. International Journal of Molecular Sciences. 2023; 24(7):6022. https://doi.org/10.3390/ijms24076022 https://www.mdpi.com/1422-0067/24/7/6022 (Full text)

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Abstract:

Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as “brain fog”, fatigue and clotting problems. Explanations for “long COVID” include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction. As conditions with sub-optimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery.
The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus. Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can “tip” the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction.
Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer’s metabolism needs to be “tipped” back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response.
Source: Nunn AVW, Guy GW, Brysch W, Bell JD. Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems. Biomedicines. 2022; 10(12):3113. https://doi.org/10.3390/biomedicines10123113 https://www.mdpi.com/2227-9059/10/12/3113 (Full text)

Altered Erythrocyte biophysical properties in Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multi-systemic illness of unknown etiology affecting millions of individuals worldwide. In this work, we tested the hypothesis that erythrocyte biophysical properties are adversely affected in ME/CFS.

We tested erythrocyte deformability using a high-throughput microfluidic device which mimics microcapillaries. We perfused erythrocytes from ME/CFS patients and from age and sex matched healthy controls (n=14 pairs of donors) through a high-throughput microfluidic platform (5μmx5μm). We recorded cell movement at high speed (4000 fps), followed by image analysis to assess the following parameters: entry time (time required by cells to completely enter the test channels), average transit velocity (velocity of cells inside the test channels) and elongation index (ratio of the major diameter before and after deformation in the test channel). We observed that erythrocytes from ME/CFS patients had higher entry time, lower average transit velocity and lower elongation index as compared to healthy controls.

Taken together, this data shows that erythrocytes from ME/CFS patients have reduced deformability. To corroborate our findings, we measured the erythrocyte sedimentation rate for these donors which show that the erythrocytes from ME/CFS patients had lower sedimentation rates. To understand the basis for differences in deformability, we investigated changes in the fluidity of the membrane using pyrenedecanoic acid and observed that erythrocytes from ME/CFS patients have lower membrane fluidity. Zeta potential measurements showed that ME/CFS patients had lower net negative surface charge on the erythrocyte plasma membrane. Higher levels of reactive oxygen species in erythrocytes from ME/CFS patients were also observed. Using scanning electron microscopy, we also observed changes in erythrocyte morphology between ME/CFS patients and healthy controls.

Finally, preliminary studies show that erythrocytes from “recovering” ME/CFS patients do not show such differences, suggesting a connection between erythrocyte deformability and disease severity.

Source: Amit K. Saha, Brendan R. Schmidt, Julie Wilhelmy, Vy Nguyen, Justin K. Do, Vineeth C. Suja, Mohsen Nemat-Gorgani, Anand K. Ramasubramanian, Ronald W. Davis. Altered Erythrocyte Biophysical Properties in Chronic Fatigue Syndrome. Biophys. Journal. VOLUME 116, ISSUE 3, SUPPLEMENT 1, 122A, FEBRUARY 15, 2019. https://www.cell.com/biophysj/fulltext/S0006-3495(18)31946-5

The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

Abstract:

BACKGROUND: Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson’s disease, schizophrenia, depression, autism, and chronic fatigue syndrome.

DISCUSSION: While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson’s disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines.

SUMMARY: This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.

 

Source: Morris G, Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med. 2015 Apr 1;13:68. doi: 10.1186/s12916-015-0310-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382850/ (Full article)

 

Modulation of the axon-reflex response to local heat by reactive oxygen species in subjects with chronic fatigue syndrome

Abstract:

Local cutaneous heating causes vasodilation as an initial first peak, a nadir, and increase to plateau. Reactive oxygen species (ROS) modulate the heat plateau in healthy controls. The initial peak, due to C-fiber nociceptor-mediated axon reflexes, is blunted with local anesthetics and may serve as a surrogate for the cutaneous response to peripheral heat. Chronic fatigue syndrome (CFS) subjects report increased perception of pain. To determine the role of ROS in this neurally mediated response, we evaluated changes in cutaneous blood flow from local heat in nine CFS subjects (16-22 yr) compared with eight healthy controls (18-26 yr).

We heated skin to 42°C and measured local blood flow as a percentage of maximum cutaneous vascular conductance (%CVC(max)). Although CFS subjects had significantly lower baseline flow [8.75 ± 0.56 vs. 12.27 ± 1.07 (%CVC(max), CFS vs. control)], there were no differences between groups to local heat. We then remeasured this with apocynin to inhibit NADPH oxidase, allopurinol to inhibit xanthine oxidase, tempol to inhibit superoxide, and ebselen to reduce H(2)O(2). Apocynin significantly increased baseline blood flow (before heat, 14.91 ± 2.21 vs. 8.75 ± 1.66) and the first heat peak (69.33 ± 3.36 vs. 59.75 ± 2.75). Allopurinol and ebselen only enhanced the first heat peaks (71.55 ± 2.48 vs. 61.72 ± 2.01 and 76.55 ± 5.21 vs. 58.56 ± 3.66, respectively). Tempol had no effect on local heating. None of these agents changed the response to local heat in control subjects. Thus the response to heat may be altered by local levels of ROS, particularly H(2)O(2) in CFS subjects, and may be related to their hyperesthesia/hyperalgesia.

 

Source: Medow MS, Aggarwal A, Baugham I, Messer Z, Stewart JM. Modulation of the axon-reflex response to local heat by reactive oxygen species in subjects with chronic fatigue syndrome. J Appl Physiol (1985). 2013 Jan 1;114(1):45-51. doi: 10.1152/japplphysiol.00821.2012. Epub 2012 Nov 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544512/ (Full article)

 

Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome

Abstract:

In chronic fatigue syndrome, several reported alterations may be related to specific oxidative modifications in muscle. Since sarcoplasmic reticulum membranes are the basic structures involved in excitation-contraction coupling and the thiol groups of Ca(2+) channels of SR terminal cisternae are specific targets for reactive oxygen species, it is possible that excitation-contraction coupling is involved in this pathology.

We investigated the possibility that abnormalities in this compartment are involved in the pathogenesis of chronic fatigue syndrome and consequently responsible for characteristic fatigue. The data presented here support this hypothesis and indicate that the sarcolemmal conduction system and some aspects of Ca(2+) transport are negatively influenced in chronic fatigue syndrome.

In fact, both deregulation of pump activities (Na(+)/K(+) and Ca(2+)-ATPase) and alteration in the opening status of ryanodine channels may result from increased membrane fluidity involving sarcoplasmic reticulum membranes.

 

Source: Fulle S, Belia S, Vecchiet J, Morabito C, Vecchiet L, Fanò G. Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome. Neuromuscul Disord. 2003 Aug;13(6):479-84. http://www.ncbi.nlm.nih.gov/pubmed/12899875