Oxidative Stress: Causes, Biomarkers & Disease

Oxidative stress is a condition that results when the body produces or consumes more reactive oxygen species (ROS) than it can neutralize. ROS are unstable molecules that can damage cells, proteins, and DNA. Oxidative stress has been implicated in a wide range of diseases, including heart disease, cancer, Alzheimer's disease, and Parkinson's disease. In this article, we will discuss oxidative stress and explore its role in disease. We will also look at some of the most common oxidative stress markers.

Oxidants and reductants can be formed in cells by losing or gaining a single electron, which makes them oxidizing or reducing agents. Oxygen, which may be converted into a variety of ROS, is the most well-known oxidizing agent. Superoxide, hydrogen peroxide, and hydroxyl radicals are all examples of reactive oxygen species. Reducing agents, on the other hand, donate electrons to other molecules and can neutralize ROS.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are terms used to describe reactive radical and non-radical derivatives of oxygen and nitrogen. Reactive oxygen and nitrogen species (RONS) are generated by all aerobic cells, and their presence has a significant impact on both age-related diseases and ageing.

ROS are produced naturally as a result of normal cellular metabolism. However, they can also be induced in reaction to external stressors such as pollution, UV radiation, and cigarette smoke. Furthermore, some medicines and medical treatments (such as chemotherapy) can cause oxidative stress to rise.

RONS causes oxidative modification of the four most important macromolecular components (carbohydrates, lipids, proteins, and DNA), which might also be used as indicators of oxidative stress.

There are a number of biomarkers that can be used to measure oxidative stress. Some of the most common ones include:

A technique to detect lipid oxidation is the thiobarbituric acid reactive substance (TBARS) test. This test measures the amount of malondialdehyde (MDA), a product of lipid peroxidation, in the blood or urine. MDA is considered to be a reliable marker of oxidative stress.

MDA is a by-product of polyunsaturated fatty acid peroxidation in cells. MDA is produced in excess when there are more free radicals. Increased levels of malondialdehyde in cancer patients is linked to an increase in free radicals.

One biomarker that is widely used to measure oxidative stress is glutathione. Glutathione is an antioxidant that helps protect cells from damage caused by ROS. Low levels of glutathione are often seen in patients with diseases associated with oxidative stress.

Glutathione is found in cells in 2 states: reduced (GSH) and oxidized (GSSG). GSH/GSSG ratio is an indication of cell redox status. Cells in good health have a GSH/GSSG ratio of more than 100, but it drops to 1 to 10 in cells subjected to oxidative stress.

The generated by-product of oxygen metabolism, superoxide, may cause a variety of cellular damage if not regulated. Superoxide dismutase is an enzyme that converts the superoxide radical to hydrogen peroxide and oxygen. Hydrogen peroxide is also hazardous and is destroyed by other enzymes, such as catalase. SOD gives essential antioxidant protection in nearly all living cells exposed to air.

Uric acid is another common biomarker for oxidative stress. Uric acid is produced when purine metabolism occurs as a result of exposure to radiation, toxins, or other sources of oxidative stress. High levels of uric acid have been linked to a number of diseases, including gout, kidney disease, and cardiovascular disease.

These biomarkers can be used to measure the level of oxidative stress in the body and help to determine its role in disease.

Oxidative stress can cause disease by damaging cells, proteins, and DNA. This damage can lead to a variety of problems, including:

All of these problems can contribute to the development of diseases like heart disease, cancer, Alzheimer's.

A number of studies have established a link between inflammation and cancer development. Chronic oxidative stress has been linked to the activation of oncogenes and the development of cancer. ROS has also been linked to cancer development by causing DNA damage, resulting in mutations.

RONS and inflammatory cytokines like TNFα activate the transcription factor NFκB, which causes genes involved in cellular proliferation, apoptosis, and cancer development to be transcribed. Chronic inflammation, in conjunction with promoting angiogenesis, has also been linked to tumour development. ROS can activate transcriptional factors such as c-fos and c-jun, which are involved in cancer development and angiogenesis. ROS-induced DNA damages can contribute to transcriptional arrest or induction/replication mistakes, as well as genomic instability.

The accumulation of amyloid plaques and neurofibrillary tangles in the brain is characteristic of Alzheimer's disease. The cause of these deposits is uncertain, but they are thought to be the result of oxidative stress. Oxidative stress, according to research, may play a role in the development and progression of Alzheimer's disease by damaging brain cells and proteins.

Increased oxidative stress biomarkers (MDA and GSH) were linked to increased levels of inflammatory cytokines in individuals with dementia. GSH levels seem to hasten cognitive decline in the elderly, despite the fact that age is the primary reason for the cognitive deterioration.

Another idea is that ROS and redox metals play a role in the development of Alzheimer's disease. Zinc, which is essential for the formation of myelin and can induce oxidative stress in its own right, may be involved in the abnormal homeostasis of bioactive metals, which might play a role in Alzheimer's disease - zinc binds to amyloid precursor protein 57 and aluminium, zinc, iron, and copper directly bind to amyloid protein promoting its aggregation.

Oxidative stress is thought to play a role in the development of heart disease. The oxidative stress theory is that it damages the endothelium's lining (the endothelium) in the arteries, resulting in inflammation. This damage and inflammation can eventually lead to the formation of plaque, which can narrow or block the arteries (atherosclerosis) resulting in an eventual heart attack or stroke.

Inflammatory responses generate oxidative stress and lower cellular antioxidant capability. Free radicals react with cell membrane lipids and proteins, destroying their function permanently.