Free Radicals and Antioxidants in Health

Free Radicals and Antioxidants in Health and Disease

• Free radicals are ionized particles in the human body

• Causes of free radicals include environmental toxins, stress, food additives, and cooking

• Free radicals are also formed during normal metabolism

• While not all free radicals are bad, they can cause damage

• Free radicals help the body fight viruses, bacteria, waste, and toxins

• The human body is composed of many different types of cells

• Cells are made of different kinds of molecules composed of protons, neutrons, and electrons

• Electrons are involved in chemical reactions and bind atoms together to form molecules

• Electrons surround atoms in one or more shells

• The innermost shell is full when it has two electrons

• The second shell is full with eight electrons

• The number of electrons in the outer shell determines an atom's chemical behavior

• A substance with a full outer shell tends not to enter chemical reactions (inert substance)

• Atoms seek stability and fill their outer shells in two ways: obtaining or losing electrons, or sharing electrons with other atoms

• Atoms often complete their outer shells by sharing electrons to form bonds

• Bonds form molecules with maximum stability

• Normally, bonds creating molecules don't split in a way that leaves a molecule with an unpaired electron

• When weak bonds split, free radicals are formed

• Free radicals are unstable and quickly react with other compounds trying to attain stability by acquiring an electron

• Free radicals are deficient in energy and snatch energy from other cells

• Free radicals are highly reactive due to their unpaired electrons

• Any free radical involving oxygen can be called reactive oxygen species (ROS)

• Oxygen-centered free radicals contain two unpaired electrons in their outer shell

• Newly formed radicals return to a ground state by stealing electrons from cellular molecules to trigger a chain reaction that can continue for thousands of events

• Damage occurs when the body has too many free radicals

• Free radicals can damage tissues, fats, proteins, and DNA

• Damage leads to diseases, and early aging

• Some free radicals arise during metabolism naturally

• Immune system cells sometimes create free radicals for neutralizing viruses and bacteria

• Free radicals can be handled, but if antioxidants aren't available, or free radical production is excessive, damage can occur

• Free radical damage accumulates with age

• Different Types of Free Radicals

  • Endogenous: arise inside the body due to various processes including metabolism, inflammation, and the mitochondrial electron transport chain
  • Exogenous: come from outside the body, such as through drugs, radiation, and environmental pollutants (including toxins in smoke)
  • Types of endogeneous free radicals include oxygen in its triplet or singlet state, hydroxyl radical (OH), nitric oxide (NO), hypochlorous acid (HOCl), hydrogen peroxide (H₂O₂), and superoxide radical (O₂⁻)
  • Other types include radicals containing carbon, hydrogen, and sulfur

• Superoxide

  • Formed from single electron transfer to oxygen's outer shell
  • Primarily generated by the electron transfer chain in mitochondria

• Hydrogen Peroxide

  • Not a free radical, but a reactive oxygen species
  • Acts as an oxidant and a significant source of hydroxyl radicals (OH)
  • Involved in the production of hypochlorous acid (HOCl) by neutrophils

• Hydroxyl Radical

  • Extremely reactive oxidizing radical
  • Reacts with many biomolecules
  • Important in radio biological damage
  • Damages virtually all kinds of macromolecules including carbohydrates, nucleic acids, fats, and amino acids

• Singlet Oxygen

  • An electronically excited form of oxygen
  • Generated by energy input like radiation or sunlight
  • Involved in joint and eye diseases

• Nitric Oxide

  • A gaseous radical
  • Plays a role in vascular physiology
  • Produced from arginine using nitric oxide synthase
  • Enhanced by cytokines, tumor necrosis factor, interleukins, and exercise
  • Inhibits microbicidal and tumouricidal activities of macrophages

• Peroxy-nitrite

  • From the reaction of nitric oxide with superoxide
  • Oxidizes many cellular compounds, DNA, and proteins
  • Causes apoptosis in cells

• Hypochlorous Acid

  • A major bactericidal agent produced by activated polymorphonuclear cells in neutrophil phagocytosing lysosomal vesicles
  • Can cross cell membranes
  • Contributes to tissue damage in the inflammatory process

• Transition Metals Ions

  • Iron and copper play significant roles in generating free radicals
  • Cause lipid peroxidation
  • Generate OH radicals from O₂ and H₂O₂

• Exogenous Free Radicals: Drugs

  • Some drugs increase free radical production, including antibiotics, antineoplastic agents, and more
  • Other drugs derived from penicillamine, phenylbutazone, and sulphasalazine may deplete antioxidants and accelerate lipid peroxidation

• Exogenous Free Radicals from Radiation

  • Radiotherapy causes tissue injury, through free radicals
  • Electromagnetic radiation and particulate radiation generate primary radicals by transferring their energy to components like water
  • These radicals undergo secondary reactions with oxygen or cellular solutes

• Exogenous Free radicals from Tobacco Smoke

  • Smoke contains many oxidant materials
  • Includes aldehydes, epoxides, peroxides, and free radicals that survive to damage alveoli
  • Elevated neutrophil levels correlate with higher free radical concentrations

• Exogenous Free radicals from Inorganic Particles

  • Inhalation of mineral dusts (asbestos, quartz, and silica) causes lung injury through free radicals
  • Linked to pulmonary fibrosis (asbestosis), mesothelioma, and bronchogenic carcinoma
  • Silica and asbestos are phagocytosed by macrophages, causing release of proteolytic enzymes, chemotactic mediators, and increased free radical and ROS production

• Ozone

  • Not a free radical, but a powerful oxidant
  • Contains two unpaired electrons
  • Degrades to OH under physiological conditions, suggesting the formation of free radicals from ozone reacting with biological substrates
  • Generates lipid peroxidation

• Other Exogenous Free Radical Sources

  • Fever, excess glucocorticoid therapy, and hyperthyroidism increase metabolism, potentially leading to increased oxygen-derived radical generation
  • Many environmental agents (air pollutants, pesticides, solvents, anesthetics, and exhaust fumes) damage cells with free radicals

• Consequences of Free Radicals

  • Many aspects of common diseases (cancer, aging, diabetes, cardiovascular disease, and more) are associated with free radical damage

• Antioxidants

  • Prevent excessive free radical damage
  • Detoxify reactive oxygen intermediates (ROI)

• Definition of Antioxidant

  • Substances that delay or reduce oxidation of substrates in low concentrations
  • Combat oxidation by reacting with free radicals and other reactive oxygen species

• Mechanisms of Antioxidants to reduce Free radicals

  • The antioxidant sacrifices itself to become oxidized while eliminating free radicals
    • The amount of antioxidants is limited, so they need to replenish themselves

• Antioxidant System

  • The body has developed several endogenous antioxidant systems (enzymes) to deal with ROI production
  • The key enzymatic antioxidants include superoxide dismutase (SOD), catalase, and glutathione peroxidase

• The glutathione redox cycle is the central mechanism for reducing intracellular hydroperoxides

  • It's a tetrameric protein with four selenium atoms, which confers catalytic activity
    • It reduces H₂O₂ to H₂O by oxidizing glutathione
    • The oxidized form of glutathione (GSSG) is reduced by glutathione reductase
    • These enzymes also requires trace metal cofactors

• Nonenzymatic Antioxidants

• Vitamins:

  • Lipid-soluble (vitamin E and vitamin A, or provitamin A)
  • Water soluble (vitamin C)
  • Glutathione (GSH)
  • These nonenzymatic antioxidants are linked to enzymatic antioxidants
  • Each antioxidant has unique roles in preventing cellular damage

• CoQ10 (Coenzyme Q10)

  • An important component in energy production in mitochondria
  • Protects the body from free radicals
  • Enhances immune defenses

• Albumin

  • Scavenges several free radicals
  • Primary component of extracellular defense systems

• Plasma Proteins

  • Ceruloplasmin and transferrin also have antioxidant activity
  • Key in various processes in the body

• Melatonin

  • A powerful antioxidant that easily crosses cell membranes and the blood-brain barrier
  • Cannot be reduced to the original form, thus classified as a "terminal" or "suicidal" antioxidant.

• Uric Acid

  • End product of purine metabolism
  • Endogenous free radical scavenger and antioxidant
  • Very reactive
  • Scavenges various radicals (singlet oxygen, peroxyl radical, OH radical)
  • Elevated uric acid levels are associated with risks like gout, heart problems, and more, but its effects are not yet fully understood

• Drugs

  • Many pharmaceuticals inhibit oxidation, including xanthen oxidase inhibitors (allopurinol, folic acid), NADPH inhibitors (adenosine, calcium channel blockers), iron redox cycling inhibitors (deferoxamine, apotransferrin, ceruloplasmin), and statins

• Dietary Sources of Antioxidants include: Fruits, Vegetables, Green Tea, and More

• Potential of Antioxidant Supplements

  • Initial studies supported benefits of antioxidant supplements, but later studies found little or no effect for preventing diseases, like cancer and heart disease
  • Supplements may be harmful in some instances
  • Antioxidants can have pro-oxidant effects

• Hormesis

  • Response to low exposure to toxins
  • May induce life span extension, but effects are not yet fully resolved

• Other Points

  • Diet plays a role in reducing oxidative damage

• Combination of antioxidants is important (not just individual components)

Explore the complex roles of free radicals and antioxidants in human health and disease. Understand the sources of free radicals and their impact on the body. This quiz will evaluate your knowledge of cellular structures and the importance of chemical reactions in maintaining stability.