Free radicals are produced by environmental sources
(air pollution, chemicals, ionizing radiation, oxidized [rancid]
fats, smoke and toxic heavy metals), immune system cells, the metabolism
of oxygen, and numerous enzymatic reactions. Some free radical activity
is required for normal physiological processes; these molecules
are manufactured and secreted by white blood cells in order to destroy
invaders such as fungi, microbes and virus. But in fending off infections,
a surplus of free radicals are produced and released into surrounding
tissue. Host cells can be damaged as well.
A normal oxygen atom has four pairs of electrons.
The body's natural metabolism can rob the atom of an electron which
changes a normal healthy cell into a chemically-altered, damaged
biological molecule - a free radical - which tries to replace the
lost electron by raiding other molecules. When a free radical takes
an electron from a cell wall, a new free radical is created, beginning
a chain reaction. The electron theft erodes the cell membrane, leading
to the disintegration/destruction of the cell. Thus the immune system
and general health can be compromised by frequent infections and
other sources of oxidative stress that introduce a cumulative and
damaging abundance of free radicals.
Each cell of the human body is equipped with a protective
means of preventing or neutralizing these free radical reactions
and repairing damage already caused by them. This protection is
found in a diverse range of molecules referred to as antioxidants.
A potent antioxidant system is manufactured by a cell in the form
of enzymes: catalase, glutathione peroxidase and superoxide dismutase;
endogenous molecules: alpha lipoic acid, bilirubin, coenzymeQ10,
glutathione, sulfhydryl groups, thioredoxin and urate; exogenous
molecules: bioflavonoids, mannitol, phenolic acid derivatives and
proanthocyanidins; and essential nutrients: carotenoids, cysteine,
selenium, and vitamins A, vitamin C and vitamin E. These molecules
can neutralize toxic forms of oxygen (free radicals) or convert
them into less dangerous products. Imbalance between free radical
production and antioxidant defense can result in oxidative stress
which can cause a depletion of these molecules, deactivation of
some enzymes, activation of others (such as proteases), DNA strand
breakage, or damage to cell membranes - allowing the leakage of
substances that can generate additional damage. Some degree of oxidative
stress occurs in most, if not all, human diseases.
It is important to note that certain antioxidants
become free radicals when they take on electrons from the free radicals
they inactivate. Medical research shows that antioxidants taken
individually do not provide a complete defense against free radicals,
since no one antioxidant destroys all free radicals, but a variety
of antioxidants taken together, commonly referred to as an antioxidant
cocktail, are more effective in enhancing the body's defense against
all free radicals. For example, after vitamins C and vitamin E destroy
free radicals, their chemical structures change and they become
free radicals (pro-oxidant), but other antioxidants such as alpha
lipoic acid and glutathione, via enzymatic reactions in cells, recharge
oxidized molecules such as vitamins C and vitamin E and recirculate
them back into their original stabilized (antioxidant) state. In
addition, when cells are exposed to nitrogen dioxide, uric acid
seems to be a major protective antioxidant, whereas it appears to
play little role as a scavenger of hypochlorous acid.
Similarly, when cells are exposed to cigarette smoke,
lipid peroxidation occurs which is inhibited by vitamin C, whereas
vitamin C has no effect on the formation of protein carbonyls by
cigarette smoke. As an extreme example, some known carcinogens that
aggravate oxidative DNA damage in vivo are powerful inhibitors of
in vitro lipid peroxidation. Thus, it is this synergistic interrelationship
among antioxidants that supports the necessity for repletion with
an antioxidant cocktail rather than repletion with an individual
antioxidant, thereby providing the cells with constant protection
from cellular damage due to excessive and varied free radical activity.
Pharmaceutical drugs that can cause antioxidant
deficiencies include acetohexamide, amitriptyline, amoxapine, aspirin,
atorvastatin, benzthiazide, beta-blockers, bumetanide, cerivastatin,
chlorothiazide, chlorpromazine, chlorpropamide, cholestyramine resin,
choline magnesium trisalicylate, choline salicylate, clomipramine,
clonidine, colchicine, colestipol, corticosteroids, desipramine,
doxepin, ethacrynic acid, fluphenazine, fluvastatin, furosemide,
glimepiride, glipizide, glyburide, haloperidol, hydralazine, hydrochlorothiazide,
hydroflumethiazide, imipramine, indapamide, isoniazid, lovastatin,
mesoridazine, methyclothiazide, methyldopa, metolazone, mineral
oil, neomycin, nortriptyline, oral contraceptives, perphenazine,
polythiazide, pravastatin, prochlorperazine, promazine, promethazine,
protriptyline, quinethazone, simvastatin, thiethylperazine, thiroidazine,
tolazamide, tolbutamide, torsemide, trichlormethiazide, trifluoperazine
and trimipramine.