Thrombosis AustraliaThrombosis Australia is a central information and resource hub for the community proudly brought to you by the Perth Blood Institute Our Thrombosis Australia Advisory Panel consists of seven eminent Australian healthcare professionals. Thrombosis Australia Advisory Panel If you are a healthcare professional you can access the Thrombosis Australia Professionals site here: Thrombosis Australia Professionals About us About Thrombosis Tools & Resources Your stories News and information What's on Get involved For professionals Oxidative stress, COVID and thrombosis Oxidative stress is an imbalance between the production of reactive oxygen species (ROS), also known as free radicals, and antioxidant defences in the body. Research indicates that free radicals play an important role in both physiological (relating to normal body functions) and pathological (caused by or related to disease) conditions. ROS at low or moderate levels have positive effects and are involved in immune function and the defence against pathogenic microorganisms. However, in higher amounts can cause oxidative stress and potential damage. High levels also have a critical role in platelet activation and are involved in health conditions such as cancer and cardiovascular disease. Recent research has found that oxidative stress, resulting from platelets and endothelial cells (ECs – cells which control the flow of fluid into and out of a tissue and line blood vessels) are closely associated with stroke-related thrombosis. Oxidative stress not only promotes primary thrombus formation by destroying ECs and platelets but additionally affects thrombus maturation. As the body ages, the risk of thrombosis increases, and research has shown that aging is also associated with the imbalance of oxidative stress and antioxidant status. An overproduction of ROS as we age can induce different physiological changes which are involved in all the processes associated with thrombosis development. As well as aging, other internal or endogenous causes of free radical production include inflammation, ischaemia, infection, cancer, excessive exercise and mental stress. Exogenous (external) risk factors include cigarette smoking, cooking (smoked meat, used oil and fat), certain drugs, heavy metals and environmental pollutants. Antioxidants The role of antioxidants is to control ‘autoxidation’ (initiated by the creation of free radicals) by interrupting the circulation of free radicals or by inhibiting their formation. Antioxidants assist with hunting the species which disrupts the autoxidative chain reaction and play a central role in the termination of oxidative chain reactions. Low molecular weight antioxidants (LMWAs) are vital for antioxidative defence mechanisms. Examples of LMWAs are vitamins, minerals, carotenoids, resveratrol, glutathione, lipoic acid, uric acid, taurine, melatonin, polyphenols and coenzyme Q10. Glutathione is a major cellular antioxidant and prevents cellular damage induced by ROS including free radicals and heavy metals. Food sources of glutathione include eggs, Brussels sprouts, broccoli, cauliflower, kale, asparagus, avocado, okra, garlic, onions and walnuts. Polyphenols are found in fruits and vegetables and are believed to protect against ultraviolet radiation and pathogens. The flavonoid (or bioflavonoids) is the most common polyphenol classes. Several studies have established that a flavonoid-rich diet is related to a lower risk of cardiovascular disease through anti-inflammatory and antiplatelet processes. The range of food sources for the different classifications of bioflavonoids is extensive; here are a few – apricots, apples, blue and red berries, red grapes, citrus fruits, garlic, onions, tomatoes, green and red capsicums. Resveratrol is part of the polyphenol group has been found to potentially interact with thrombin (platelet activation protein) and the coagulation process. This antioxidant has also exhibited anticoagulant and antifibrinolytic abilities in some studies. Food sources of resveratrol include grapes, peanuts and soy. Antioxidant minerals include copper, magnesium, zinc and selenium. Important vitamins include ascorbic acid or vitamin C and Vitamin E. Coenzyme Q10 (CoQ10) or Ubiquinone is a potent antioxidant as it counteracts ROS and protects the inner lining of blood vessels. Fish and meat contain the highest level of CoQ10 along with liver, kidney, heart, sardines and peanuts. Superoxide dismutases (SODs) are another crucial component in the body which targets oxidative stress. SODs are common antioxidant enzymes which control the levels of a variety of reactive oxygen species, therefore limiting their potential toxicity. There are three types of SOD, comprising of manganese, iron, or copper and zinc. SODs have been found to provide protection against oxygen toxicity and the damaging sequelae of prolonged inflammation. SOD occurs naturally in barley grass, broccoli, Brussels sprouts, cabbage, wheatgrass and most green plants. Oxidative stress and COVID-19 Unusual or abnormal platelet activity and oxidative stress are significant causes of thrombotic disorders among COVID-19 patients. Oxidative stress, provoked by the excessive generation of ROS, could increase platelet function and the risk of blood clots. The antioxidant activity of CoQ10 demonstrates strong anti-platelet effect. Recent research has found that the protective effect of CoQ10 on the SARS-CoV-2 spike protein-potentiated platelet aggregation is possibly associated with its strong antioxidative capacity. Please consult your GP if choosing to start any nutrient supplementation as some may interfere with certain drugs and therapies. PBI research Perth Blood Institute is studying the role that Gamma Prime Fibrinogen (GPF) plays in various inflammatory disease states. The Long COVID Syndrome Study (GPF LoCov Study) will be investigating novel biomarkers in patients with acute and long COVID. As GPF is also an inflammatory marker associated with cardiovascular disease, a secondary aim of the study is to see if there is a correlation between GPF and other coagulation, inflammatory and endothelial markers. PBI and our research team at Murdoch University are collaborating with researcgers from the University of Medicine and Health Services in Ireland to investigate the relationship between the COVID-19 infection and effects on blood proteins. The project will analyse blood samples from COVID-19 infected patients to study the fundamental causes and mechanism of disease progression. The team will examine the coagulation cascade and biomarkers involved and address a knowledge gap in the interplay between COVID-19 and thrombosis. References What is oxidative stress? - PubMed (nih.gov) An update on the role of free radicals and antioxidant defense in human disease - PubMed (nih.gov) Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases - PMC (nih.gov) Oxidative stress, aging, and diseases - PMC (nih.gov) ijms-21-04259.pdf (nih.gov) Autoxidation - an overview | ScienceDirect Topics Food Sources of Glutathione | livestrong Flavonoids: an overview - PMC (nih.gov) Plant foods and herbal sources of resveratrol - PubMed (nih.gov) Superoxide Dismutase - an overview | ScienceDirect Topics Appiah, D. et al. (2015). Association of plasma γ' fibrinogen with incident cardiovascular disease: The atherosclerosis risk in communities (ARIC) study. Arterioscler Thromb Vasc Biol.;35(12):2700-6. doi: 10.1161/ATVBAHA.115.306284. Balch, P.A. 2006. Prescription for nutritional healing (4th). Penguin Group. Hassan, H.M. & Fridovich, I. (1981). Chemistry and biochemistry of superoxide dismutases. Eur J Rheumatol Inflamm. 4(2): 160-172. Li, Z., Bi, R., Sun, S., Chen, S., Chen, J., Hu, B. & Jin, H. (2022). The role of oxidative stress in acute ischemic stroke-related thrombosis. Oxid Med Cell Longev. 16:doi:10.1155/2022/8418820 Pizzino, G. et al. (2017). Oxidative Stress: harms and benefits for human health. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2017/8416763 Szewc, M. et al. (2022). The role of zinc and copper in platelet activation and pathophysiological thrombus formation in patients with pulmonary embolism in the course of SARS-CoV-2 infection. Biology 11, https://doi.org/10.3390/biology11050752 Tan, B.L. et al. (2018). Antioxidant and oxidative stress: A mutual interplay in age-related diseases. Front Pharmacol. 16;9:1162. doi:10.3389/fphar.2018.01162. Violi, F., & Pignatelli, P. (2012). Platelet oxidative stress and thrombosis. Thromb Res. 129(3): 378-81. doi:10.1016/j.thromres.2011.12.002 Wang, Q. & Zennadi, R. (2020). Oxidative stress and thrombosis during aging: the roles of oxidative stress in RBCs in venous thrombosis. International Journal of Molecular Sciences, 21(12): doi:10.3390/ijms21124259 Wang, Y., Branicky, R., Noë, A., & Hekimi, S. (2018). Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol;217(6):1915-1928. doi: 10.1083/jcb.201708007.