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Dr Anu Chandran
Department of pharmacology
Trivandrum medical college
*Definition: a free radical is any atom (e.g.
oxygen, nitrogen) with at least one unpaired
electron in the outermost shell, and is
capable of independent existence
*Unstable molecule
*They seek out to capture
electrons to neutralize
themselves
*Another free radical
formed
*Chain of reaction sets in
*Within seconds thousands
of free radicals formed
*A free radical is formed when a
covalent bond between entities
(atoms) is broken and one electron
remains with each newly formed
atom
 Electron transport chain
drug metabolism by CYPs
phagocytosis.
Transition metals present in
the body ( e.g. Fe, Cu etc.),.
(they have variable oxidation
numbers ,so can accept or
donate electons)
*Ionizing radiations,
*Heavy metals,
* Cigarette,
* Alcohol intake
*Pollution
*Pesticides
*Insecticides
*
* Oxidize the biomolecules leading to
tissue injury and cell death.
*After initiation, the chain can
propagates to form a vicious cycle
inducing further damage.
*Destroys PUFA of cell membranes
*Destabilises membrane receptors
*Inactivate enzymes
*Breaks DNA strands
* involved in physiological
processes like ageing and
pathologically in diseases with
multi organ involvement.
*Carcinogenesis (due
to DNA damage)
*Rheumatiod arthritis
*Amyloidosis
*CNS – Parkinson’s
disease
*CVS – Myocardial
infarction,
Atherosclerosis.(LDL
oxidatin)endothelial
dysfuction
*GIT – Peptic ulcer,
Cirrhosis, Pancreatitis
*Renal – Nephrotoxicity
due to
glomerulonephritis /
Heavy metals.
*Respiratory – asthma
*Vision –
Cataract,Retinopathy.
Substances that neutralize free radicals
or their actions
Limit free radical formation
Destroy free radicals
Stimulate antioxidant enzyme
activity
Endogenous enzymatic anti oxidants are constituted
by three major enzyme groups
*Superoxide Dismutase
*Catalase
*Peroxidase
*An imbalance in the oxidant to anti oxidant
levels lead to a condition termed oxidative
stress.
*increased generation and impaired
degradation of the free radicals.
*Impaired degradation in conditions like
amyotrophic lateral sclerosis (ALS), where
there are presumed decreases in
superoxide dismutase.
*α tocoferol has the highest vit
E activity
Dietary source
*Wheat germ oil, vegetable
seed oil, nuts, egg yolk, peas.
Physiological role as anti-oxidant
*Prevents oxidation of coenzyme Q
* protects poly unsaturated fatty acids from
oxidative break down( lipid peroxidation)
*tocopherol phenoxyl radical
*Major chain breaking antioxidant
*Protection against cancer, coronary artery
disease, AD and cataracts.
*400 IU to 800 IU( daily recommentation)
Dietary source
*Citrus fruits
*Tomatoes
*Potatoes
*Green Chillies
*Cabbage
*Reacts with H2O2, peroxide and
super oxide to get oxidised to
dehydroascorbate.
*Carcinogenic effect of tobacco
through nitrosamines are inhibited
by Vit C & E
*Deficiency can predispose to
atherosclerosis and
carcinogenicity.
*60 mg ( daily recommentation)
*Biologically active
*Naturally occurring chemical
compounds
*Found in plants
*Act as natural defense for
host plants
*Provide color and flavor
*Beta carotene
*Lycopene
*Limonoids
*Precursor of vitamin A
*ANTIOXIDANT
*RED color – tomato , water
melon ,papaya,gauva
• LIMONOIDS
– citrus fruits
*Sulphur containing phytochemicals
Cruciferous vegetables like
braccoli,cabbage ,watercres
Onion ,garlic
*Antioxidant role - anticancer role
especially for lung and GIT cancer
*Blue berries
,grapes,cherries,red apple
*Green tea black tea
*Soyabeans
*LOO˙ + FL - OH LOOH + FL - O˙
*Flavonoid phenonyl radical
*Act as phytoestrogen
*Bind to estrogen receptors
*Actions
Increase bone density
Decrease serum cholesterol
Decrease post cancer prostrate
growth
Decrease hormone dependent
cancer( anti estrogen effect)
*Blue green algae
*Good source of SOD ,B carotene and B
complex vitamin
*Most powerfull food on earth
*Fat soluble antioxidant
*Present in mitochondria
*Decline with age
*100 to 200 mg/day
*Benefit in PD and CHF
a. N acetyl cysteine – glutathione
precursor
b. Ebselen – congener of glutathione
* Both augment endogenous
glutathione peroxidase activity
* Anti oxidant effect of n acetyl
cysteine is used in paracetamol
poisoning
c) Desferoxamine,
Cerulloplasmin
*Binds free Fe2+, binds superoxide
anion
*Inhibit iron dependant lipid
peroxidation
*Used in AD, RA, reperfusion injury
d) Selenium
*Enhances the antioxidant
effect of Vit E
*Promotes synthesis of
glutathione peroxidase
*Immunostimulant
e) Mn,Zn, Cu, Cr
*Also augments the synthesis
of anti oxidant enzymes (SOD,
GP, Catalase)
f)Xanthine oxidase inhibitors
(Allopurinol, Oxypurinol)
*Xanthine oxidase generates
super oxide free radicals from
reduced flavins
*Important in reperfusion
injury after ischemia
*NSAIDs
*ACE Inhibitors
*CCBs
*Selegiline
Antioxidants

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Antioxidants

  • 1. Dr Anu Chandran Department of pharmacology Trivandrum medical college
  • 2.
  • 3. *Definition: a free radical is any atom (e.g. oxygen, nitrogen) with at least one unpaired electron in the outermost shell, and is capable of independent existence
  • 4.
  • 5. *Unstable molecule *They seek out to capture electrons to neutralize themselves *Another free radical formed *Chain of reaction sets in *Within seconds thousands of free radicals formed
  • 6. *A free radical is formed when a covalent bond between entities (atoms) is broken and one electron remains with each newly formed atom
  • 7.  Electron transport chain drug metabolism by CYPs phagocytosis. Transition metals present in the body ( e.g. Fe, Cu etc.),. (they have variable oxidation numbers ,so can accept or donate electons)
  • 8. *Ionizing radiations, *Heavy metals, * Cigarette, * Alcohol intake *Pollution *Pesticides *Insecticides *
  • 9.
  • 10. * Oxidize the biomolecules leading to tissue injury and cell death. *After initiation, the chain can propagates to form a vicious cycle inducing further damage.
  • 11. *Destroys PUFA of cell membranes *Destabilises membrane receptors *Inactivate enzymes *Breaks DNA strands * involved in physiological processes like ageing and pathologically in diseases with multi organ involvement.
  • 12. *Carcinogenesis (due to DNA damage) *Rheumatiod arthritis *Amyloidosis *CNS – Parkinson’s disease *CVS – Myocardial infarction, Atherosclerosis.(LDL oxidatin)endothelial dysfuction *GIT – Peptic ulcer, Cirrhosis, Pancreatitis *Renal – Nephrotoxicity due to glomerulonephritis / Heavy metals. *Respiratory – asthma *Vision – Cataract,Retinopathy.
  • 13.
  • 14. Substances that neutralize free radicals or their actions Limit free radical formation Destroy free radicals Stimulate antioxidant enzyme activity
  • 15.
  • 16. Endogenous enzymatic anti oxidants are constituted by three major enzyme groups *Superoxide Dismutase *Catalase *Peroxidase
  • 17.
  • 18.
  • 19. *An imbalance in the oxidant to anti oxidant levels lead to a condition termed oxidative stress. *increased generation and impaired degradation of the free radicals. *Impaired degradation in conditions like amyotrophic lateral sclerosis (ALS), where there are presumed decreases in superoxide dismutase.
  • 20.
  • 21.
  • 22. *α tocoferol has the highest vit E activity Dietary source *Wheat germ oil, vegetable seed oil, nuts, egg yolk, peas.
  • 23. Physiological role as anti-oxidant *Prevents oxidation of coenzyme Q * protects poly unsaturated fatty acids from oxidative break down( lipid peroxidation) *tocopherol phenoxyl radical *Major chain breaking antioxidant *Protection against cancer, coronary artery disease, AD and cataracts. *400 IU to 800 IU( daily recommentation)
  • 24.
  • 26. *Reacts with H2O2, peroxide and super oxide to get oxidised to dehydroascorbate. *Carcinogenic effect of tobacco through nitrosamines are inhibited by Vit C & E *Deficiency can predispose to atherosclerosis and carcinogenicity. *60 mg ( daily recommentation)
  • 27. *Biologically active *Naturally occurring chemical compounds *Found in plants *Act as natural defense for host plants *Provide color and flavor
  • 29. *Precursor of vitamin A *ANTIOXIDANT
  • 30. *RED color – tomato , water melon ,papaya,gauva • LIMONOIDS – citrus fruits
  • 31. *Sulphur containing phytochemicals Cruciferous vegetables like braccoli,cabbage ,watercres Onion ,garlic *Antioxidant role - anticancer role especially for lung and GIT cancer
  • 33. *LOO˙ + FL - OH LOOH + FL - O˙ *Flavonoid phenonyl radical
  • 34. *Act as phytoestrogen *Bind to estrogen receptors *Actions Increase bone density Decrease serum cholesterol Decrease post cancer prostrate growth Decrease hormone dependent cancer( anti estrogen effect)
  • 35. *Blue green algae *Good source of SOD ,B carotene and B complex vitamin *Most powerfull food on earth
  • 36. *Fat soluble antioxidant *Present in mitochondria *Decline with age *100 to 200 mg/day *Benefit in PD and CHF
  • 37.
  • 38. a. N acetyl cysteine – glutathione precursor b. Ebselen – congener of glutathione * Both augment endogenous glutathione peroxidase activity * Anti oxidant effect of n acetyl cysteine is used in paracetamol poisoning
  • 39. c) Desferoxamine, Cerulloplasmin *Binds free Fe2+, binds superoxide anion *Inhibit iron dependant lipid peroxidation *Used in AD, RA, reperfusion injury
  • 40. d) Selenium *Enhances the antioxidant effect of Vit E *Promotes synthesis of glutathione peroxidase *Immunostimulant e) Mn,Zn, Cu, Cr *Also augments the synthesis of anti oxidant enzymes (SOD, GP, Catalase)
  • 41. f)Xanthine oxidase inhibitors (Allopurinol, Oxypurinol) *Xanthine oxidase generates super oxide free radicals from reduced flavins *Important in reperfusion injury after ischemia

Editor's Notes

  1. Copper zinc and manganese part of SOD - cofactors