Measurement and evaluation of biomarkers of oxidative stress, inflammation, haemorheology and whole blood antioxidant capacity in healthy, rheumatoid arthritis and Parkinson’s disease populations

Diane Hughes

Research output: ThesisDoctoral Thesis

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Abstract

There is substantial evidence to implicate oxidative stress and inflammation in the pathology of Parkinson’s disease; the second most common neurodegenerative disease. Oxidative stress and systemic inflammation are well established as fundamental to rheumatoid arthritis pathophysiology. For both diseases, erythrocyte oxidative stress is reported but there is no consensus across the literature on erythrocyte antioxidant activities. Contradictory results might be due to methodology and/or disease stage and progression.

Whilst transporting oxygen and carbon dioxide, erythrocytes scavenge free radicals from all tissues and if overwhelmed by free radicals cellular components can become damaged by oxidation. Once oxidised, proteins and membrane lipids can alter erythrocyte morphology. Altered erythrocyte morphology subsequently affects the rheological parameters of erythrocyte deformability, aggregation and consequently whole blood viscosity.

The initial aim of this thesis was to determine if erythrocyte redox enzyme balance is altered in Parkinson’s disease when analysed by early and later stage disease status. The impact of hypothesised erythrocyte oxidative stress upon erythrocyte morphology and haemorheology was also investigated. Rheumatoid arthritis patients were included as a group with established inflammation and erythrocyte oxidative stress for further comparison of Parkinson’s disease with both a healthy control group and an oxidative stress affected group.

Introducing the thesis is a brief summary of key information behind the rationale of the thesis studies. Crucial information about oxidative stress and inflammation is presented. The two disease states studied are briefly described, followed by study significance and hypotheses. Chapter 2 provides a review of the relevant literature and includes analysis of original studies underpinning the thesis.

The aim of study one was to measure peripheral inflammation, erythrocyte antioxidant enzyme activity levels and morphology in Parkinson’s disease, using both a healthy control group and an oxidative stress and inflammation related group of rheumatoid arthritis patients. Results were correlated with haemorheological changes. Plasma and erythrocyte biochemistry was tested, and erythrocyte morphology assessed using scanning electron microscopy. A cone and plate viscometer and ektacytometer tested whole blood viscosity, erythrocyte deformability and aggregation. Chapter 3 reports increased erythrocyte stomatocytes in both rheumatoid arthritis and Parkinson’s disease that correlated with several erythrocyte antioxidant enzyme activities. Inflammation was increased in rheumatoid arthritis, but not in early stage Parkinson’s disease. Chapter 4 reports unchanged whole blood viscosity, despite some haemorheological changes.

Study two (chapter five) focused on whole blood total antioxidant capacity in both diseases, extending study one by using a new methodology; chemiluminescence. Results of this study demonstrate whole blood has higher antioxidant capacity due to synergistic interaction of plasma and erythrocyte antioxidants with polyphenols, platelets and lymphocytes. Oxidative stress was increased in rheumatoid arthritis whole blood, but Parkinson’s disease whole blood demonstrated increased antioxidant capacity.

Lastly, the major findings of the thesis are discussed. In summary, the overall profile of Parkinson’s disease erythrocyte antioxidant enzyme activity, erythrocyte morphology, haemorheology and whole blood total antioxidant capacity is more similar to the oxidative stress related rheumatoid arthritis disease group than to healthy controls. This research also provides evidence that erythrocyte redox balance changes in Parkinson’s disease as disease stage advances.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Charles Sturt University
Supervisors/Advisors
  • Richards, Ross, Principal Supervisor
  • Lexis, Louise, Co-Supervisor, External person
Thesis sponsors
Place of PublicationAustralia
Publisher
Publication statusPublished - 2018

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