Contents

Free radicals
Anti-oxidants
Classification
Mode of action
Therapeutic uses
 Free Radicals
Free radical is any chemical species that is capable of
independent existence containing one or more unpaired
electrons, the unpaired electron being one is that is alone in
an orbital.

Characteristic features:
Highly reactive
Very short half-life
Can generate new radicals by chain reaction
Cause damage to biomolecules, cells and tissues
 Significant free radicals
Singlet state
Superoxide anion
Hydroxyl radical
Nitric oxide
Peroynitrite
Hypochlorous acid
Hydrogen peroxide
Alkoxyl radical
Peroxyl radical
 ANTIOXIDANTS
Any substance which when present in
low concentration relative to that of
the oxidizable substrate significantly
delays or inhibits oxidation of that
substrate.
Halliwell & Gutteridge, 1989
 CLASSIFICATION
Antioxidants in relation to lipid peroxidation
1. Preventive antioxidants - catalase, glutathione
peroxidase
2. Chain breaking antioxidants - superoxide
dismutase, vitamin E, uric acid
Antioxidants according to their location
1. Plasma antioxidant - B carotene, ascorbic acid,
bilirubin, uric acid, ceruloplasmin, transferrin
2. Cell membrane antioxidant - a- tocopherol
(Vitamin E)
3. Intracellular antioxidant - superoxide dismutase,
catalase, glutathione peroxidase
 CLASSIFICATION
Antioxidants according to their nature and action

1. Enzymatic antioxidant - superoxide dismutase,

catalase, glutathione peroxidase, glutathione reductase

2. Non-enzymatic antioxidant
1. Nutrient antioxidant - carotenoids, B carotene, a-
tocopherol, ascorbic acid, selenium
2. Metabolic antioxidant - glutathione,
ceruloplasmin, albumin, bilirubin, transferrion,
uric acid
 1. Glutathione
Tripeptide composed of amino acid i.e. gamma-glutamyl-
cysteinyl-glycine
Glycine metabolized to form glutathione
Present in reduced or oxidized form

MOA
Preventive antioxidants
Intracellular antioxidant
Enzymatic antioxidant
Functions

Co-enzyme for certain enzymes eg: protaglandin PGE2

synthetase

Prevents oxidation and helps in protein function

Reduced glutathione
Maintains RBC membrane structure and integrity
Protects hemoglobin from getting oxidized by agents
such as H2O2

Toxic amounts of peroxides and free radicals are scavenged

 2. Selenium
MOA
Non-enzymatic antioxidant
Nutrient antioxidant
Protects the cells against the damage caused by H2O2
Maintains the structural integrity of biological membrane
Prevents lipid peroxidation and protects against free radicals
including superoxide
Prevents carcinogenesis
Binds with heavy metals and protects from its toxic effects

Daily intake: 50-200mg Se recommended for adults

Sources: Organ meats(liver, kidney) and sea foods
 3. Vitamin A
Fat soluble vitamin A present only in Retinol (Vitamin A Alcohol)
foods of animal origin
Provitamins Beta Carotene found in
plants
Retinoids include natural and synthetic Retinal (Vitamin A
forms of Vitamin A Aldehyde)
Retinol, Retinal and Retinoic acid
regarded as vitamers
Beta carotene (Provitamin A) Retinoic Acid (Vitamin A
cleaved in the intestine by beta acid)
caritene 15-15 dioxygenase to
steroid hormone
release 2 moles of retinal
Daily Intake: growth and differentiation
3,500 IU for man
2,500 IU for woman
 3.a. Retinoids
MOA Used
Non-enzymatic Oral Leukoplakia
antioxidant Oral Lichen planus
Nutrient Oral Submucous Fibrosis
antioxidant Oral Squamous Cell Carcinoma

Actions
Main function :
Role in growth, differentiation
Anti-proliferatives and apoptosis
which regulate
Anti-keratinizing
epithelial cell
Supresses carcinogenesis
growth
Tumor suppressive activity
 3.b.Carotenoids
Family of antioxidant phytonutrinet
Alpha-carotene, Beta-carotene, Lutein and Lycopene
3.b.(i).
Natural pigments synthesized by plants and micro-
orgaminsms but not animals

Primarily present in adipose tissues(80-85%), Liver (8-12%),

Muscle(2-3%) and smaller amounts in other tisues
Dose: Beta carotene 90mg/day

MOA
Non-enzymatic antioxidant
Nutrient antioxidant
 3.b.(i). Lycopene

Bright red carotenoid pigment and

phytochemical found in Tomatoes,
carrot, watermelon, papaya
Fat soluble
Important intermediate in the
biosynthesis of many carotenoids, i.e.
beta carotene
Actions
Serve as antioxidant
Enhance the immune
response
Reduce photo-induced
neoplasm
Inhibit mutagenesis
Dose: 8mg Lycopene/day Oral Squamous Cell
then 4mg
Oral Submucous
Fibrosis
Stimulate the immune
system or direct action on
the tumor cells
Inhibits fibrogenesis by
inhibiting the abnormal
fibroblast
Oral Leukoplakia
Low moderate grade
Prevents progression of
dysplasia by inhibiting tumor cell
proliferation
Carcinoma
prevented by preventing
premalignant lesions and their
progression into OSCC
Antioxidant activity by ROS
scavenging, prevents
carcinogenesis by interference
with cell cycle proliferation,
increase in p53 protein level
Inhibit tumor angiogenesis
4. Alpha- Tocopherol (Vitamin E)
commonest and most active form of vitamin-E.
Other forms and antioxidant activity are: alpha>
beta> gamma>delta
Lipid soluble found in biological membranes.
Found in plant oil, margarine, and green leaves.

MOA:
Chain breaking antioxidant
Cell membrane antioxidant
Non-enzymatic antioxidant
Nutrient antioxidant
 Main actions includes:

Free radical scavenging

Maintenance of membrane integrity
Immune function
Inhibition of cancer cell growth/differentiation
Inhibition of DNA and RNA, protein synthesis in
cancer cells.
Inhibits mutagenicity and nitrosamine formation

Dose
Vitamin E 400 IU BD for 24weeks
 Vitamin E in oral diseases
Inhibits oral cavity carcinogenesis.
Reduces the risk of developing oral cancer.
Causes reversal of premalignant lesion like oral
leukoplakia

Used in
Oral leukoplakia
Oral Lichen Planus
Oral Submucous Fibrosis
Oral Squamous Cell Carcinoma
 5. Ascorbic Acid (Vitamin C)
water soluble present in citrus fruits,
potatoes, green leafy vegetables
MOA:
Plasma antioxidant
Essential for Non-enzymatic
Anti-mutagenic effects antioxidant
Block the formation of
mutagenic N-Nitroso compounds Nutrient
Antioxidant property antioxidant
Immunological function
Increases neutrophil function Daily Intake:
Enhances wound healing by collagen
formation 60-70mg per day
Prevents lipid peroxidation
Bibliography
Biochemistry U. Satyanarayana, U. Chakrapani 4th Edition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253290/
https://www.ncbi.nlm.nih.gov/pubmed/15570034
http://www.juniordentist.com/oral-manifestation-or-signs-of-
vitamin-deficiency.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542334/