Antioxidants
Antioxidants
are substances whose presence in
relatively low concentration
significantly inhibit the rate of
OXIDATION of the major targets of
oxidative activity viz., cell
membranes & components, proteins
and other cellular constitutes.
The
antioxidants that are therapeutically
available are conveniently divided as;
1. Natural antioxidants
(Physiological)-normally present in
the body
2. Pharmacological antioxidants
(Synthetic)
Within
each group three categories of
antioxidants have been recognized
viz.,
- Antioxidant
enzymes catalyzing the breakdown
of Free radicals
-
Preventative
antioxidants (sequestration of
metal ions)- those which prevent
the participation of transition
metal ions in free radical
generation.
-
Those
which are Free radical SCAVENGERS
(Chain breaking) Antioxidants.
Natural
Antioxidants:
a) Enzyme
Antioxidants-
-
Super
oxide Dismutase (SOD)
intracellular removes superoxide
radical by speeding their
dismutation.
- Catalase
intracellular removes H2O2
-
Glutathione
Peroxidase Selenium containing
enzyme removes H2O2
and other peroxides, regenerates
ascorbate from dehydroascorbate
and detoxification of
xenobiotics.
b) Natural
Preventive Antioxidants:
- Transferrin
& lactoferrin
-
Caeruloplasmin
Cu containing has ferroxidase
activity, prevents Fe++
from reacting with H2O2.
-
Albumin
=SH- groups contribute to chain
breaking antioxidants
c) Natural
Chain Breaking antioxidants:
-
Ascorbic
acid potent inhibitor of lipid
peroxidation (25-100 umol/L)
regenerates tocopherol.
-
Uric
acid, bilirubin, thiols etc.
-
Tocopherol
(20-30 micro mol/L) Major
chain breaking antioxidant and
oxides to un-reactive tocopherol
radicals.
-
Beta
carotene Lipid soluble
Retinol (Vitamin A) precursor
synergises with tocopherol in
Lipid peroxidase.
-
Ubiquinol-10
Reduced from Coenzyme Q10
-
Flavonoids
fruit, vegetables &
wing plays a contributory role.
-
Estrogens-
some activity has been detected in
vitro but not in vivo.
Pharmacological Antioxidants:
a)
Augmenting
antioxidant enzymes
-
S
O D Generated by recombinant
synthesis in pharmacological
doses, SOD may reduce adherence
neutrophils to endothelium
-
Catalase
Liposome encapsulated or PEG
conjugated
b)
Preventive
Antioxidant
-
Desferoxamine
Iron chelator useful in
Thalassemia
c)
Scavenging
(Chain breaking antioxidants)
-
Probucol
Retards atherosclerosis,
regression of Lipid deposits (Xanthlasma)
-
Salicylates
NSAIDs have antioxidant and
radical scavenging effects.
-
Lazaroids
(21 aminosteroids)
Inhibits iron dependent Lipid
peroxidation.
-
Mannitol,
Dimethyl sulfoxide, Dimethyl
thiourea Hydroxy radical
scavengers.
-
Drugs
: Captoril, Beta Blockers, Calcium
antagonists, cinnarizine,
amiodarone, NSAIDs,
Methylprednisolone etc.,
d)
Xanthine
Oxidase Inhibitors
-
Allopurinol
and Oxypurinol
Neutrophil
& Macrophage inhibitors (NADPH
oxidase inhibitors) Ex; adenosine,
NSAIDs, Ca antagonists
Antineutrophil
serum depletes circulating
neutrophils
-
Antiadhesion
agents Monoclonal antibodies
CD11/CD18.
General principles of Antioxidant therapy
Before
contemplating antioxidant therapy, the
below mentioned questions need to be
answered. The most important aspect is
to consider whether the patient really
needs antioxidant therapy and if so
the rationale behind the decision.
-
Whether
the oxidative damage has been
implicated in the disease
pathophysiology.
-
Whether
the oxidative activity is central
to the pathophysiology of the
disease or an epiphenomenon.
-
Whether
there is a known antioxidant
defect.
-
Whether the oxidative damage is occurring.
-
Whether
the antioxidant reaches sufficient
concentration at the site of
action.
-
Whether
the antioxidant will have an
impact on oxidation process in
vivo
-
Whether
the antioxidant can be given and
if so can it be tolerated at the
necessary doses.
-
If
prolonged therapy is needed
whether it will be safe
-
Whether
antioxidant can be given safely.
