Oxidative Stress: Effects on the body and how to reduce it

What is oxidative stress? Effects on the body and how to reduce it

It is a good question, isn’t it? After all, what is oxidative stress? You have likely heard of this term before. If not, you have undoubtedly heard of antioxidants. Antioxidants fight against oxidative stress.

Oxidative stress was formulated as a concept in biology and medicine in 1985. That’s fairly new, as far as the history of science goes. But research on this topic has exploded over the past few decades.

PubMed currently has 233,289 journal articles using the term “oxidative stress.” After reading this article, you will understand why oxidative stress has become necessary in the medical community.

What is oxidative stress?

Oxidative stress results from an imbalance between pro-oxidants and antioxidants. This leads to cellular damage and free radicals. Oxidative stress is an imbalance between ROS production and the antioxidant defense systems.

People often misuse the term “oxidative stress.” It refers to the reduction-oxidation chemistry only. The field of oxidative chemistry embraces chemistry, biochemistry, cell biology, physiology, and pathophysiology. It also involves medicine as well as health and disease research. 

Aerobic metabolism involves a steady balance between reduction and oxidation. Any potential strains in the balance evoke an oxidative stress response.

Oxidative stress is an inevitable event in a healthy human cell. Oxidative stress is responsible for the functioning of vital metabolic processes. These include insulin signaling and the production of erythropoietin. Oxidative stress alters the profile of transcription factors.

Oxidative stress isn’t necessarily a bad thing, as long as it is appropriately balanced out.

What are free radicals?

A free radical is any molecule that contains one or more unpaired electrons. This uneven number of electrons allows them to react with other molecules easily.

Since free radicals react so quickly with other molecules, they can cause long chain chemical reactions. This is called oxidation. Oxidation can be beneficial. But it can also be harmful, as we will soon discuss.

Free radicals are produced through physiological aerobic metabolism or pathological inflammatory processes. Oxidation can cause acute and chronic dysfunction.

However, they can also provide essential control of redox-regulated signaling pathways. Free radicals are generated by oxygen metabolism. This should be balanced by the rate of oxidant formation and the rate of oxidant elimination. 

Radicals are a normal byproduct of several metabolic pathways. Some exist in a controlled form and perform essential functions. Others exist in a free form. They interact with various components of the tissue.

Two different types of free radicals are reactive oxygen species and reactive nitrogen species. ROS have molecular oxygen as their free radical. They may be small molecules, but free radicals are critical to cell functions and biological processes. When it comes to free radicals, they must be properly balanced.

What are antioxidants?

Antioxidants help to avoid the negative consequences of free radicals by neutralizing them. Most antioxidant defense happens due to antioxidant enzymes. Antioxidants are both nutrigenetic and nutridynamic in nature.

Antioxidants have an electron available to donate to a free radical. The unique thing about antioxidants is that they can do this without making themselves unstable. This leads to the free radical being more stable and less reactive.

The primary effect of antioxidants is that they prolong the lag time before a free radical chain reaction.

Antioxidants have powerful effects on preventing premature lipid peroxidation in food. This decreases the generation of lipid peroxides. This suggests that these same compounds could act as dietary antioxidants. Consuming a diet high in antioxidants can help to prevent various diseases.

There is a tumor suppressor protein called p53. P53 is responsible for regulating a variety of signaling pathways. The past decade of research shows us that p53 helps to mediate the burden of oxidative stress. With low to moderate oxidative stress, p53 activates pathways to increase time for cell repair.

These include things like cell cycle arrest and autophagy. They help to enhance cell survival. With high oxidative stress, p53 initiates DNA fragmentation. This helps to induce cell death in order to prevent cell proliferation. This happens with radiation, low oxygen (hypoxia), and oxidizing agents.

What causes oxidative stress?

Oxidative stress includes biochemical, physiological, and pathological stimuli. In short, an excess of ROS generation causes oxidative stress. An imbalance in the oxidant and antioxidant mechanisms lead to a state of oxidative stress.

But what causes this imbalance in the first place? There is a host of lifestyle-related factors that predominantly cause oxidative stress. The good news is that most of these lifestyle factors are modifiable.

A high intake of macronutrients can promote oxidative stress. These include dietary carbohydrates, animal-based proteins, and fats. This is because they contribute to the long term consequences of nutritionally mediated inflammation. This is why caloric restriction becomes important.

Several molecular event cascades cause oxidative stress. These include the following molecular pathways:

  • Glycolytic

  • Hexosamine

  • Protein kinase C

  • Polyol

  • Advanced glycation end-product pathways (called AGE pathways for short)

Oxidative stress occurs in diabetes and insulin resistance. Poly ADP ribose polymerase 1 seems to be responsible for this. It inhibits glyceraldehyde 3 phosphate dehydrogenase, which then accumulates and leads to oxidative stress. It does this by activating the AGE pathway.

It also activates protein kinase C pathways by promoting the synthesis of diacylglycerol. It also causes the accumulation of glycolytic metabolites upstream. This then leads to excessive stimulation of even more oxidation pathways. These include hexosamine and polyol pathways.

Patients with chronic kidney disease usually have multiple cardiovascular risk factors. These include diabetes, high cholesterol, and high blood pressure. All these conditions are associated with oxidative stress. This then triggers the inflammatory process and further accelerates injury to the kidneys.

Other causes of oxidative stress include the following:

  • Exercise

  • Malnutrition

  • Alcoholism

  • Chronic hepatitis C infection

  • Chronic hepatitis B infection

  • Human immunodeficiency virus (HIV) infection

  • Preexisting liver disease

  • Environmental oxidizing agents

  • Tissue manipulation

  • Irradiation

  • Hypoxia

  • Excessive consumption of linoleic acid

Damage caused by oxidative stress

Oxidative stress can have a result of damage throughout the body. Read below to see how it can affect different organs and body systems.

Atherosclerosis

Atherosclerosis is the build-up of plaque on the interior walls of the arteries. Oxidative stress is a critical, final common mechanism in atherosclerosis.

Reactive oxygen species (called ROS for short) are critical to vascular homeostasis. However, the uncontrolled production of reactive species is part of vascular injury.

Infertility

Oxidative stress is a leading cause of defective sperm function. High levels of oxidative stress lead to damage to sperm DNA. It also leads to damaged RNA transcripts and telomeres. Oxidative stress is a common underlying cause of male infertility and recurrent pregnancy loss.

It also can lead to congenital malformations, complex neuropsychiatric disorders, and childhood cancers in the offspring. This is all because spermatozoa are highly vulnerable to oxidative stress. This is due to their limited antioxidant defense. They also only have a single, limited DNA damage detection and repair mechanism.

Hypertension

Recent studies show that oxidative stress is an important cause of endothelial cells’ injury. Oxidative stress can lead to more production of pro-oxidants. These pro-oxidants include superoxide anion hydrogen peroxide.

Oxidative stress also leads to less creation of nitric oxide, helping to relax and dilate blood vessels. Oxidative stress is also related to the following aspects of cardiovascular disease:

  • Endothelial dysfunction

  • Inflammation

  • Hypertrophy (growth of the heart)

  • Apoptosis (cell death)

  • Cell migration

  • Fibrosis

  • Angiogenesis (creation of new arteries)

Heart failure

Reactive oxygen species are involved in the genesis and maintenance of volume and pressure overload. Overload produces myocardial ischemia. This is a lack of blood flow to the heart. 

During ischemia, there is an increase in xanthine and xanthine oxidase. There is also a decrease in the superoxide dismutase and glutathione peroxidase activity. This leads to an increase in oxygen-free radicals. 

During ischemia, cellular pH decreases. This triggers the release of phospholipase. This, in turn, releases arachidonic acid from phospholipids. Arachidonic acid metabolism creates leukotrienes and prostaglandins, which are pro-inflammatory. 

During arachidonic acid metabolism, oxygen-free radicals are produced. But so too are molecules of LTB4. This is leukotriene that activates neutrophils and triggers increased secretion of oxygen free radicals. 

Increased circulatory catecholamines also lead to an increase in oxygen-free radicals. Hydroxyl radicals decrease the binding of calcium ions. They also decrease uptake of the sarcoplasmic reticulum. Calcium ions and the sarcoplasmic reticulum are responsible for muscle contraction. So when they are decreased, there is less efficient contractility of the heart muscles. 

Overall, oxygen-free radicals decrease cardiac function and contractility of the muscles of the heart.

Age-related macular degeneration

Oxidative stress has a pathological role in the degeneration of retinal pigment epithelium. This contributes to the development of age-related macular degeneration.

Autism spectrum disorders

Oxidative stress in pregnant women has a relationship to the development of autism in her offspring.

Other damage caused by oxidative stress

Oxidative stress can result in other damage throughout the body. This includes the following:

Free radicals can damage fatty tissue, DNA, and proteins. Since fats, DNA, and proteins make up most of the tissue in your body, this damage can be detrimental.

What are the risk factors?

Free radicals are normal to have in the body in small amounts. Even things like exercise and minor inflammation can cause oxidation. This is normal and healthy.

Many different factors increase your risk of oxidative stress. These include the following:

  • High intake of macronutrients (especially sugar, fat, and alcohol)

  • Polyunsaturated fatty acid (PUFA) residues of phospholipids and cholesterol esters

  • NADPH oxidase

  • Aging

  • Environmental stresses

  • Cigarette smoking

  • High fat intake in the diet

  • Chronic kidney disease

  • High uric acid levels in the blood

  • Risk in the offspring if the mother consumes a diet high in animal fat while pregnant

  • Ozone

  • Pesticides

  • Certain cleaning products

  • Pollution

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Managing and preventing oxidative stress

Based on recent research, it seems a better idea to maintain redox balance in the cell. This is better than an excessive outside supply of antioxidant supplementation in humans. This interferes with antioxidant homeostasis.

It is impossible to completely avoid free radicals and oxidative stress. You can minimize the effects of oxidative stress on your body, however. Your best bet is to decrease your formation of free radicals. This stops the problem before it even starts. This tackles the root cause of the problem of oxidative stress.

Total antioxidant capacity (TAC) is a way to assess the antioxidant status. It is a way to evaluate the antioxidant response against free radicals produced in a given disease.

There are several ways you can help to prevent oxidative stress. You can also manage the oxidative stress already existing in your body. Here are a few things that can help:

  • Aspirin

  • Statin drugs

  • Renin-angiotensin system inhibitors

  • Yoga

  • Meditation

  • Caloric restriction

  • Natural polysaccharides

  • Alpha-tocopherol (commonly known as vitamin E)

  • Ascorbic acid (commonly known as vitamin C0

  • Polyphenols

  • Angiotensin-converting enzyme inhibitors (called ACE inhibitors for short)

  • Beta-blockers

  • Dihydropyridine calcium channel blockers

  • Aloe (leaf’s skin, flowers, and gel)

  • Tea

  • Niacin (commonly known as vitamin B3)

  • Coenzyme Q10

  • Melatonin

  • Omega-3 fatty acids

  • Coffee

  • Gingko Biloba

  • Coleus

  • Tropical fruits

  • Berries

  • Cherries

  • Citrus fruits

  • Prunes

  • Dark leafy green vegetables

  • Broccoli

  • Carrots

  • Tomatoes

  • Olives

  • Fish

  • Nuts

  • Turmeric

  • Onion

  • Garlic

  • Cinnamon

  • Reactive oxygen species scavengers that perform the following actions:
    • Target mitochondrial reactive oxygen species
    • Have newer nanotechnology-based frug delivery systems
    • Gene expression therapies
    • Anti mitochondrial ribonucleic acids (anti-mRNAs)
    • Synthetic LOX-1 modulators that inhibit the effects of oxidized LDL (what we call “bad cholesterol”)

Oxidative stress is a healthy body function. But when it is not balanced out properly with antioxidants, the disease can result. This is why it is important that you do prevent excessive oxidative stress within your body. Preventing oxidative stress is easier than trying to reverse it. Reversing oxidative stress is possible, however.

You may want to consider avoiding the causes of oxidative stress that are listed above. Look out for any oxidative stress markers. Lower your risk factors as much as possible. And it really is possible. Although certain risk factors are unavoidable, such as aging, most are preventable. Improve your diet and lifestyle.

Do keep in mind that pumping your body full of antioxidant supplements may not be the best course of action. Some antioxidant therapy is helpful, but lifestyle modifications need to happen too.

If you are interested in minimizing your oxidant stress, speak to your healthcare provider today. They may be able to prescribe you medications or recommend supplements that can be helpful.

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