Antioxidants and Free Radicals Quiz

Free Radicals and Antioxidants

• Free radicals are ionized particles in the human body.
• They can be caused by environmental toxins, stress, food additives, and cooking.
• Free radicals are also formed during normal metabolism when oxygen is used by the body.
• Not all free radicals are bad.
• They help fight viruses, bacteria, waste, and toxins.
• The human body is composed of many different types of cells.
• Cells are composed of molecules and atoms consisting of protons, neutrons, and electrons.
• Electrons are involved in chemical reactions and bond atoms together to form molecules.
• Electrons surround, or orbit, an atom in one or more shells.
• The innermost shell is full with two electrons.
• When the first shell is full, electrons fill the second shell, and so on, with eight electrons in the second shell.
• The number of electrons in the outer shell determines an atom's chemical behavior.
• A substance with a full outer shell is usually inert and doesn't readily react in chemical processes.
• Atoms reach maximum stability by gaining or losing electrons to fill or empty their outer shells or by sharing electrons to complete their outer shells through bonding.
• Atoms share electrons to be bound together and reach maximum stability in a molecule.
• Normally, bonds don't split in a way that leaves a molecule with an unpaired electron.
• However, when weak bonds split, free radicals are formed.
• Free radicals are unstable and react quickly with other compounds to gain stability by capturing needed electrons.
• Free radicals are like robbers deficient in energy.
• They attack and snatch energy from other cells to satisfy themselves.
• Free radicals are highly reactive due to unpaired electrons.
• Any free radical involving oxygen can be called reactive oxygen species (ROS).
• Oxygen-centered free radicals have two unpaired electrons in the outer shell.
• The newly formed free radical looks to return to its ground state by stealing electrons from cellular structures or molecules.
• This chain reaction continues and can last thousands of events.
• Damage occurs when the body has too many free radicals.
• Free radicals affect tissues, lipids, proteins, and DNA.
• Damaged cells can lead to disease and early aging.
• The effects of free radical damage increase over time, leading to age-related diseases.
• Some free radicals arise normally during metabolism.
• The body's immune system creates these free radicals to neutralize viruses and bacteria.
• The body usually handles free radicals, but damage can occur if antioxidants are unavailable or free-radical production is excessive.
• Free radical damage typically accumulates with age.

Types of Free Radicals

• The most important free radicals in the body are radical derivatives of oxygen (reactive oxygen species).
• Reactive oxygen species include oxygen in its triplet or singlet state, hydroxyl radical, nitric oxide (NO), hypochlorous acid (HOCl), hydrogen peroxide (H₂O₂), and superoxide radical (O⁻₂).
• Other free radicals are carbon-centered free radicals arising from oxidizing radicals attacking organic molecules.
• Hydrogen-centered radicals result from hydrogen atom attacks.
• Sulfur-centered radicals form from glutathione oxidation.
• Superoxide free radical anion forms when oxygen is reduced by electron transfer to its outer shells.
• The electron transfer chain in the mitochondria is the major source of superoxide.
• Superoxide itself is not particularly damaging.
• Hydrogen peroxide (H₂O₂) is not a free radical but part of the reactive oxygen species category.
• It's an oxidizing agent, but its main significance lies in its role as a source of hydroxyl radicals.
• Hydrogen peroxide is generated from two superoxide molecules forming hydrogen peroxide and oxygen. This is called a dismutation reaction.
• The hydroxyl radical is very reactive and can react with many biomolecules.
• The hydroxyl free radical is significant in radiation-induced biological damage.
• The hydroxyl radical damages carbohydrates, nucleic acids, lipids, and amino acids.

Mechanisms to Scavenge Hydroxyl Radicals

• Endogenous antioxidants (like melatonin and glutathione), and dietary antioxidants (like phytochemicals and vitamin E) are mechanisms to scavenge hydroxyl radicals for cellular protection.

Singlet Oxygen

• Singlet oxygen (¹O₂) is an electronically excited form of oxygen.
• It's similar to normal oxygen but has an extra electron.
• Singlet oxygen is generated by energy input, such as radiation or sunlight.
• It's involved in joint and eye diseases.
• Carotenoids (like vitamin A and lycopene) and vitamin E can neutralize singlet oxygen.

Nitric Oxide

• Nitric oxide (NO) is a gaseous free radical.
• It's important in vascular physiology and is also known as endothelium-derived relaxing factor.
• Endothelial cells produce nitric oxide from arginine using nitric oxide synthase.
• Cytokines, tumor necrosis factor, and interleukins also stimulate NO production.
• Exercise also stimulates it.
• Inhibiting nitric oxide production reduces macrophage microbicidal and tumouricidal activity.

Peroxynitrite

• Peroxynitrite is formed from the reaction of nitric oxide and superoxide.
• It's an oxidizing agent damaging DNA and proteins and can cause cell apoptosis.

Hypochlorous Acid

• Activated polymorphonuclear cells (PMNs) produce hypochlorous acid (HOCl) as a major bactericidal agent.
• This reaction occurs in the neutrophils' phagocytic lysosomal vesicles.
• Hypochlorous acid crosses cell membranes.
• It may contribute to tissue damage during inflammation.

Transition Metals

• Iron and copper play a role in generating free radicals, facilitating lipid peroxidation.
• Transition metal ions generate hydroxyl radicals (OH) from O₂⁻ and H₂O₂.
• This reaction accelerates the non-enzymatic oxidation of molecules like epinephrine and glutathione, creating more O₂ and H₂O₂, and then OH.

Exogenous Free Radicals

• Drugs can increase free radical production.
• For example, antibiotics like nitrofurantoin, antineoplastic agents like bleomycin, anthracyclines like adriamycin, and methotrexate can increase free radical production.
• Radicals from penicillamine, phenylbutazone, and sulphasalazine can inactivate proteases and deplete ascorbic acid, increasing lipid peroxidation.

Radiation

• Radiotherapy can cause tissue injury from free radicals.
• Electromagnetic radiation (X-rays, gamma rays) and particulate radiation (electrons, photons, neutrons, alpha and beta particles) generate radicals by transferring their energy to cellular components like water. These primary radicals have secondary reactions with dissolved oxygen or cell contents.

Tobacco Smoking

• Each puff of smoke carries substantial oxidant materials (aldehydes, epoxides, peroxides, other free radicals), which can persist and damage alveoli.
• Tar contains relatively stable free radicals.
• Smokers have higher neutrophil levels in the lower respiratory tract, which could elevate free radical concentration further.

Inorganic Particles

• Inorganic particle inhalation (e.g., asbestos, quartz, silica) leads to lung injury probably mediated by free radical production.
• Asbestos is linked to pulmonary fibrosis, mesothelioma, and bronchogenic carcinoma.
• Silica and asbestos activate pulmonary macrophages, causing cell rupture and releasing proteolytic enzymes and chemotactic mediators, leading to increased free radical and reactive oxygen species production.

Ozone

• Ozone (O₃) is a powerful oxidant but not a free radical, but it degrades to OH, implying free radical formation when ozone interacts with biological substrates..
• Ozone can induce lipid peroxidation.

Other Factors

• Fever, excessive glucocorticoid therapy, and hyperthyroidism increase metabolism, leading to increased oxygen-derived radical production.
• Various environmental factors (chemical air pollutants, pesticides, solvents, anesthetics, exhaust fumes) trigger free radical damage to cells.

Free Radicals and Disease

• Free radicals contribute to diseases like cancer, aging, diabetes, and cardiovascular disease.

Antioxidant Functions

• Antioxidants detoxify reactive oxygen intermediates (ROI).
• Antioxidants have received interest as treatments for various diseases (cancer, atherosclerosis, chronic inflammatory diseases, aging).

Antioxidant Definitions

•  Antioxidants are substances that delay or reduce oxidation of substrates when present in low concentrations.
•  They protect other body chemicals from damaging oxidation reactions by reacting with free radicals and other reactive oxygen species.
•  Antioxidant molecules sacrifice themselves through oxidation. They only have a single reaction with each free radical, so replenishment is needed.

Antioxidant Systems

• The body has developed several endogenous antioxidant systems to manage ROI production.
• These systems include superoxide dismutase (SOD), catalase, and glutathione peroxidase, effectively managing reactive oxygen species.

Glutathione Redox Cycle and Nature

• The glutathione redox cycle is a central mechanism for reducing intracellular hydroperoxides.
• It's a tetrameric protein containing four selenium atoms, thus being catalytically active.
• Glutathione peroxidase oxidizes glutathione while reducing hydrogen peroxide to water.
• Oxidized glutathione is reduced to its initial state catalytically by glutathione reductase.

Trace Metals

• Enzumatic antioxidants (like SOD, catalase, and glutathione peroxidase) require trace metal cofactors for optimal function.
• Trace metals include selenium (for glutathione peroxidase), copper, zinc, or manganese (in SOD), and iron (in catalase).

Nonenzymatic/Exogenous Antioxidants

• Nonenzymatic antioxidants include lipid-soluble vitamins (vitamin E, vitamin A or provitamin A, like beta-carotene), water-soluble vitamin C, and glutathione (GSH).
• These antioxidants are also linked to each other in the body.

Antioxidant Classification

• Classify major antioxidants (SOD, catalase, glutathione peroxidase) based on their role (e.g., dismutases, oxidizers), presence (e.g., mitochondria, cytosol, peroxisomes), and associated use of GSH (e.g., superoxide).

Vitamin E

• Protects against lipid peroxidation and is a lipid-soluble antioxidant.
• Vitamin E can neutralize free radicals and react to prevent lipid peroxidation.
• Vitamin C regenerates used vitamin E.
• Supplementation could also increase plasma and tissue levels of E in the body.
• Vitamin E protects membrane phospholipids and against cell membrane damage.
• Vitamin E also plays a role in immune stimulation.

Beta Carotene

• Carotenoids are pigments in fruits and vegetables.
• Beta-carotene is a precursor to vitamin A and acts as an antioxidant.
• Beta-carotene is widely studied, consisting of combined vitamin A.
• Dietary beta-carotene converts into retinol in the intestinal mucosa.
• Beta-carotene's antioxidative role is linked to singlet oxygen quenching and scavenging free radicals.
• Autoxidation is the process where carotenoids can undergo oxidation.
• Carotenoids also promote immunity, inhibit mutagenesis and transformation, and regress precancerous lesions.

Ascorbic Acid (Vitamin C)

• Water-soluble antioxidant abundant in citrus fruits, potatoes, tomatoes, and leafy greens.
• Acts as a chain-breaking antioxidant, scavenging free radicals and reactive oxygen species.
• Prevents carcinogen formation from precursors and helps detoxification pathways.
• It is more effective than vitamin E in inhibiting LDL oxidation.
• Vitamin C helps to regenerate vitamin E.

Other Antioxidants

• Glutathione (GSH): Crucial intra-cellular antioxidant formed from cysteine, glycine, and glutamate.
• GSH is involved in the redox cycle, and it also scavenges hydroxyl radicals and singlet oxygen.
•  CoQ10 (Coenzyme Q10): A ubiquinone vital for energy production in mitochondria. Protects against free radicals and enhances immunity.
• Albumin: Also scavenges free radicals in the extracellular system.
• Plasma proteins, such as ceruloplasmin and transferrin, exhibit antioxidant actions.

Melatonin

•  Powerful antioxidant that readily crosses cell membranes and the blood-brain barrier.
• Unlike other antioxidants, does not undergo redox cycling.
• Once oxidized, melatonin cannot be reduced to its original state. So it's called a terminal antioxidant.

Uric Acid

• Acts as an endogenous radical scavenger and antioxidant.
• A byproduct of purine metabolism, present in body fluids.
• Uric acid scavenges singlet oxygen, peroxyl, and hydroxyl radicals (OH).
• High uric acid levels can act as a pro-oxidant.
• Elevated uric acid could be a risk factor for gout, atherosclerosis, ischemic stroke and heart attacks.

Drug-Based Antioxidants

• Some pharmaceutical agents have antioxidant effects: Xanthine oxidase inhibitors (allopurinol, folic acid); NADPH inhibitors (adenosine, calcium channel blockers); iron redox cycling inhibitors (deferoxamine, transferrin, and ceruloplasmin); and statins.

Dietary Sources of Antioxidants

• List of foods rich in various antioxidants(by food type and antioxidant type).

Antioxidant Supplements

• Antioxidant supplements may NOT have long-term health benefits in chronic diseases or cancer.
• Benefits of fruits and vegetables likely come from complex combinations of compounds (e.g., flavonoids) and other substances.
• Some antioxidants can behave as pro-oxidants, paradoxically damaging cells—increasing oxidative stress.

Hormesis and Free Radicals

• Hormesis refers to favourable biological responses to low levels of stressors or toxins.
• Free radicals can induce an endogenous response to protect against exogenous radicals (and other harmful compounds).
• Induction of endogenous free radical production by low doses of compounds can extend lifespan (mito-hormesis).

Important Points

• Diet is crucial to reduce oxidative damage.
• Dietary antioxidants aren't limited to just vitamins, minerals, or chemicals but include complex combinations of these.
• Antioxidant pills haven't shown effects on lifespan, and health improvement, as needed.

Test your knowledge about the role of antioxidants in the body and their relationship with free radicals. This quiz covers sources of free radicals, health issues linked to oxidative stress, and essential vitamins known for their antioxidant properties.