Oxidative Stress (OS) refers to the imbalance between oxidation and anti-oxidation in the body, tends to oxidize, leads to inflammatory infiltration of neutrophils, increased secretion of proteases, and produces a large number of oxidative intermediates. Oxidative stress is a negative effect produced by free radicals in the body and is considered to be an important factor in aging and disease. Oxidative stress reflects an imbalance between the systemic performance of reactive oxygen species and the ability of biological systems to readily detoxify or repair damaged intermediates. Disorders in the normal redox state of cells can cause toxic effects by the production of peroxides and free radicals that destroy all components of the cell, including proteins, lipids and DNA. Oxidative stress from oxidative metabolism can lead to base damage and DNA strand breaks. The destruction of alkali is mainly indirect and is caused by the production of reactive oxygen species (ROS). O2-(superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). In addition, some reactive oxidizing species act as cell messengers in redox signaling. Thus, oxidative stress can lead to disruption of the normal mechanisms of cellular signaling.
The quantitative evaluation methods of oxidative stress are roughly divided into three categories:
1 determining a compound modified with active oxygen;
2 measuring the amounts of enzymes and antioxidant substances in the active oxygen elimination system;
3 Determination of an oxidative stress indicator containing a transcription factor.
Understanding these points is useful for clinical outreach. However, in clinical practice, the quantification of oxidative stress is still problematic. Because oxidative stress is closely related to various diseases, it lacks specificity, and its quantitative indicators are difficult to use for specially designated diseases. Therefore, it is currently considered to be used for "systemic evaluation" or for the evaluation of "severity and after" after the cause of the disease is oxidative stress. Representative biomarkers:
8-OHdG is a sensitive DNA damage marker formed by the attachment of a hydroxyl group to the eighth carbon of guanine. However, its oxidation "is induced by hydroxyl radicals generated by oxidative stress". In recent years, many antioxidant substances have been used for clinical intervention experiments, and it is expected to achieve anti-aging and disease prevention by reducing 8-OHdG.
It is reported that diseases that can cause 8-OHdG to rise include chronic viral hepatitis, systemic lupus erythematosus, colorectal cancer, and gastritis caused by Helicobacter pylori infection. It is further understood that lifestyles can also increase 8-OHdG, such as smoking and drinking, strenuous exercise, exposure to supersaturated UV/radiation, etc. People are exploring what lifestyles should be used to control the level of 8-OHdG. Guide to life, maintaining the health of the individual.
Figure 1. Chemical structure of 8-hydroxydeoxyguanosine.
TRX is one of the important redox regulatory molecules in the cell; when it is stimulated by various infections such as viral infection, ultraviolet rays and environmental pollutants, it will induce its intracellular expression. Even if TRX is present alone, it can exhibit the elimination of singlet oxygen and hydroxyl radicals. In addition to being used as an antioxidant, it can also be used as a disulfide bond of a reducing protein. Further, in terms of synaptic transmission, TRX is able to inhibit the activation of ASK1 and p38 MAPK. Furthermore, it was recognized that TRX was also released extracellularly, showing its cytokine/chemokine-like effect. It has been reported that in the relationship with human diseases, the increase in TRX concentration can occur in the serum of HIV-infected patients and hepatitis C patients. In addition, it has been noted that TRX can be effectively evaluated for diseases such as autoimmune diseases including rheumatoid arthritis, ischemia-reperfusion injury, and chronic heart failure, which can cause oxidative stress.
Figure 2. Structure of Thioredoxin.
Oxidative stress-caused diseases
The consequence of high free fatty acid (FFA) stimulation is the increased production of highly active reactive molecules oxygen clusters (ROS) and reactive nitrogen clusters (RNS), which initiates oxidative stress mechanisms (high activity molecular production and antioxidant activity). Long-term imbalance between the two causes tissue damage). These active molecules directly oxidize and damage DNA, proteins, lipids, and act as functional molecular signals to activate a variety of stress-sensitive signaling pathways in cells that are closely related to insulin resistance and impaired beta cell function.
Beta cells are also important targets of oxidative stress β cells have lower levels of antioxidant enzymes and are therefore more sensitive to ROS. ROS can directly damage islet β cells, promote β cell apoptosis, and indirectly inhibit β cell function by affecting insulin signaling pathway. Impaired beta cells, decreased insulin secretion levels, delayed secretion peaks, and increased blood glucose fluctuations make it difficult to control the rapid rise in postprandial blood glucose and cause more significant damage to cells.
Low-density lipoprotein (LDL) deposition in the arterial intima is an atherosclerosis (AS) initiating factor. Under the action of ROS secreted by vascular cells, "primitive" LDL becomes oxidized LDL (ox-LDL), stimulating endothelial cells. Secretion of a variety of inflammatory factors, induce monocyte adhesion, migration into the arterial intima, and transformation into macrophages. ox-LDL also induces macrophages to express scavenger receptors and promote their uptake of lipoproteins to form foam cells. At the same time, ox-LDL is a NADPH oxidase activator, which can enhance its activity, promote ROS production, and is more conducive to the oxidation of LDL to ox-LDL. In addition, ox-LDL can inhibit NO production and its biological activity, resulting in abnormal vasodilation