Paradox of Aerobic Life

Oxidation and how it plays a role in disease?

Technically, oxidation is the chemical process by which an atom, molecule, or ion robs another of one or more of its electrons. Chemicals exhibiting this tendency for stealing electrons are referred to as oxidizing agents. Perhaps the most familiar oxidizing agent is oxygen itself. We can see many examples of oxygen doing its electron stealing in our everyday lives: the browning of an apple, the rusting of an iron nail, the slow fading of blue jeans. When a material is oxidized, its chemical structure is altered, often irreversibly. The human body is no exception.

We are constantly exposed to oxidative stress. This stress is partly brought on by environmental parameters, such as air pollution, tobacco smoke, exposure to chemicals, and exposure to ultraviolet (UV) light or other forms of ionizing radiation (Møller et al. 1996; Papas 1999).

Partly, however, oxidative stress in animals, including humans, arises as a natural result of the body sustaining itself by aerobic (oxygen-requiring) metabolism (Ames et al. 1993; Davies 1995). Normal aerobic metabolism produces as its by-products various highly reactive molecules, collectively termed “oxidants”. These oxidants include a variety of electron-stealing molecules known as free radicals, as well as the highly reactive singlet form of oxygen (Darley-Usmar and Halliwell 1996). Some of these reactive molecules (e. g., superoxide, hydrogen peroxide, and nitric oxide) are physiologically useful and, in fact, are necessary for life, but can also be harmful if present in excess or in inappropriate situations.

All of these oxidants can react with various components of a living cell, such as proteins, DNA, or lipids (fats), thus causing damage by changing the chemical structure of these components. Such damage has been linked to a number of pathological conditions including aging (Harman 1981; Ames and Shigenaga 1992), atherogenesis (Steinberg et al. 1989; Esterbauer et al. 1992), ischemia-reperfusion injury (Simpson and Lucchesi 1987; Takayama et al. 1992), infant retinopathy (Phelps 1987), age-related macular degeneration (Gerster 1991), and carcinogenesis (Moody and Hassan 1982; Marnett 1987; Breimer 1990).

For us, oxygen is therefore both necessary and harmful; this sobering conclusion has been referred to as the “paradox of aerobic life” (Davies 1995).

The human body has evolved a large array of endogenous antioxidant defenses against oxidative stress, including antioxidant enzymes such as superoxide dismutase (SOD), catalase, and various peroxidases, as well as the ability to use small molecules with antioxidant activity such as glutathione (Fahey and Sundquist 1991), the hormone melatonin (Reiter et al. 1997; Reiter 1998), and uric acid (Yu et al. 1998).

However, these endogenous antioxidants do not completely protect against the sum of oxidative stresses challenging the body, and thus there is net oxidative damage that in the long term contributes to aging and various diseases. In addition to the body’s endogenous defenses against oxidative stress, diet-derived antioxidants–including ascorbic acid (Vitamin C), alpha-tocopherol (Vitamin E), and the carotenoids–may be important in protecting against disease and age-related phenomena (Ames et al. 1993; Davies 1995; Halliwell 1996).

Diet-derived antioxidants may be classified on the basis of their solubility as either lipid-soluble (i. e., soluble in fats), or water-soluble. Lipid-soluble antioxidants include vitamin E and the carotenoids (astaxanthin, beta-carotene, lycopene), while vitamin C is a common water-soluble antioxidant.

In what diseases has oxidation been implicated?

Many human diseases and degenerative processes have been linked in some way to the action of free radicals. Free radicals are not necessarily the only cause for these conditions, but may well make the human body more susceptible to other disease-initiating factors, may enhance the progression of diseases, and may inhibit the body’s own defenses and repair processes.

The following conditions involving multiple organs have all been linked to free radicals (Cross et al. 1987):

  • Cancer
  • Aging (including immune deficiency with aging and premature aging disorders)
  • Radiation injury
  • Alcohol damage
  • Ischemia-reperfusion injuries
  • Inflammatory-immune injuries (including vasculitis from drugs and hepatitis B virus, idiopathic and membranous glomerulonephritis, and autoimmune diseases)
  • Reactions induced by drugs and toxins
  • Iron overload (including idiopathic hemochromatosis, dietary iron overload, thalassemia and other chronic anemias)
  • Amyloid diseases

In addition, a number of single-organ conditions have been related to free radicals (Cross et al. 1987):

  • Affecting the brain–senile dementia, neurotoxin reactions, hyperbaric oxygen effects, Parkinson’s disease, cerebral trauma, hypertensive cerebrovascular injury, allergic encephalomyelitis and other demyelinating diseases, neuronal ceroid lipofuscinoses, ataxia-telangiectasia syndrome, potentiation of traumatic injury, aluminum overload
  • Affecting erythrocytes (red blood cells)–lead poisoning, protoporphyrin photo-oxidation, malaria, sickle-cell anemia, favism, Fanconi anemia
  • Affecting the lungs–emphysema, hyperoxia, cigarette-smoke effects, oxidant pollutant effects, acute respiratory distress syndrome, bronchopulmonary dysplasia, mineral dust pneumoconiosis, bleomycin toxicity, paraquat toxicity
  • Affecting the heart and cardiovascular system–atherosclerosis, stroke, doxorubicin toxicity, peripheral circulation problems, Keshan disease (selenium deficiency), alcohol cardiomyopathy
  • Affecting the kidney–renal graft rejection, nephritic antiglomerular basement membrane disease, heavy metal nephrotoxicity, aminoglycoside nephrotoxicity
  • Affecting joints–rheumatoid arthritis
  • Affecting the gastrointestinal tract and liver–endotoxin liver injury, carbon tetrachloride liver injury, diabetogenic action of alloxan, free fatty acid-induced pancreatitis, abetalipoproteinemia, nonsteroidal anti-inflammatory drug-induced lesions
  • Affecting the skin–sunburn and solar radiation injury, thermal injury, porphyria, contact dermatitis, Bloom syndrome, effects of photosensitive dyes
  • Affecting the eyes–age-related macular degeneration, ocular hemorrhage, degenerative retinal damage, cataractogenesis, retinopathy of prematurity, photic retinopathy

It is quite clear that human health depends to a large extent on the body’s ability to control free radicals and thus reduce oxidative damage to tissues, cells, and DNA. To that end, antioxidants play an essential role in disease prevention, in longevity, and in overall well-being.

Read further on antioxidants, free radicals, free electrons, red-ox balance, …all  related to healthy living and aging in the book “Enjoyvity, your full spectrum of life”  and at .

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