FREE RADICAL AND OXYGEN TOXICITY- Prof FAY

OBJECTIVES
- Enable students to understand and appreciate what Free Radicals are and their relevance to health and Disease States.
- Educate students on the Sources of Free Radicals and how they are generated.
- Help students appreciate Free Radical reactions and Mechanism of Action:
- Lipid Peroxidation
- DNA Destruction
- Antioxidant Systems/Sources
- Assist students in understanding the extent to which Reactive Oxygen Species (ROS) contribute to the aetiogenesis of Disease States.
EXPECTED OUTCOME
- At the end of the course, students would have attained a strong foundation for understanding the application of Free Radical Reactions (ROS) and their Health Implications, which will be relevant in their Clinical Practice.

Free radicals are caused by the body’s own natural processes, with excesses created from toxins, radiation, and poor digestive function.
The body generates free radicals at an astonishing speed daily. Normally, the body can handle these free radicals, but cellular damage can occur if antioxidants are unavailable or free radical production becomes excessive.
Free radicals are a major cause of aging and declined health; they cause cell mutations, damage immune function, contribute to wrinkles and aging, and are implicated in diseases such as cancer, cardiovascular disease (CVD), arthritis, Alzheimer’s, and Parkinson’s disease.
The antidote to free radicals is antioxidants, some of which are produced by the body while others are supplied through diet (fruits, vegetables). Environmental influences increase the body's need for antioxidants beyond production and dietary sources.

Oxygen Toxicity: The overall toxic effect of oxidative free radical species at the cellular level.
Free Radicals: Any species capable of independent existence that contains one or more unpaired electrons.
Reactive Oxidative Species (ROS): A collective term for oxygen-centered radicals and some non-radical derivatives of oxygen.
Oxidative Stress: The overall effect of oxidative species causing tissue injury or disease.

Internally Generated Sources:
- Mitochondria
- Phagocytes
- Xanthine oxidase
- Reactions involving iron and other transition metals
- Arachidonate pathways
- Peroxisomes
- Exercise
- Inflammation
- Ischemia/reperfusion
Externally Generated Sources:
- Cigarette smoke
- Environmental pollutants
- Radiation
- Ultraviolet light
- Certain drugs, pesticides, anesthetics, and industrial solvents
- Ozone

Atoms comprise smaller units called electrons, with stable molecules carrying pairs of electrons.
Free radicals carry unpaired electrons, which seek to pair with electrons from neighboring molecules, causing a chain reaction that damages cells and DNA.
Free radicals form at an astonishing rate in the body.

Oxygen is fundamental to free radical formation, necessary for metabolism and energy production.
Environmental sources (e.g., tobacco smoke, radiation, chemicals) and physiological stressors (e.g., exercise, or disease) can lead to free radical production.
Examples of Free Radicals:
- Trichloromethyl - CCl3
- Superoxide - O2·
- Hydroxyl - OH·
- Thiyl - RS·
- Peroxyl, alkoxyl - R O2·, R O·