Antioxidants & Free radicals

Hepatoprotective

Dr.dr.Asep Sukohar, M.Kes

 What are Reactive Oxygen
Species?
 ROS also known as Free oxygen radicals
 Any molecule with an unpaired electron
 Extremely chemically reactive
 Damage cell membranes
 Responsible for more than 100 human diseases
 Aging, cancer, heart attacks, stroke and arthritis
 Some beneficial effects
 How are ROS Formed?
 Primary source is our body during energy
production
 Environmental contaminants
 Ionizing and ultraviolet radiation
 Prolonged low blood flow states
(atherosclerosis, heart attacks and stroke)
 Diet (fatty and processed foods)
 Low levels of antioxidants
 Protection from ROS
Damage
 Superoxide dismutase
 Catalase
 Glutathion
 Antioxidants in diet
 Supplementation
Aging and Effect on Antioxidant
Enzymes
 Significant decline in SOD
 Significant decline in catalase and glutathione
 Significant decline in energy production
 Cellular, tissue and system aging and failure
 Scientific Support for
Antioxidants
 Animals with longer life spans have higher
antioxidant levels
 Dietary increase in antioxidants increase
life span
 Caloric restriction (reduces ROS
formation) leads to significantly increased
life span
 Questions asked
 What are free radicals?
 Types of free radicals
 Sources of free radicals
 Oxygen metabolism
 Discussion on oxidative damage and
oxidative stress
 What is antioxidant?
 Natural free radical defense systems
 What are Phytochemicals?
 Free radical-Mediated
Diseases
 Diseases of the old -
Chronic and degenerative diseases
(diabetes, cataracts, Alzheimer’s disease, cancers,
cardiovascular disease, hepatitis and aging)

 Diseases of the young and innocent -

Acute and immature diseases
(Eyes: retinopathy of prematurity, Lung:
bronchopulmonary displasia, Brain: cerebral pulsy,
Pancreas: Type 1 diabetes)
 What are free radicals?

 Any molecule containing one or

more unpaired electrons
 Types of Free Radicals
 Reactive Oxygen Species (ROS) -

 Reactive Nitrogen Species (RNS) - NO.

 Reactive Metabolites or Intermediates
- metabolic activation of drugs, toxins,
pollutants, cigarette smokes, etc.
Reactive Oxygen Species (ROS)

.
 Superoxide (O2 -)
 Hydrogen Peroxide (H2O2)
 Hydroxyl Radical (OH.) - product of
Fenton reaction catalyzed by free Fe and Cu
 Singlet Oxygen (1DgO2) - oxygen at an
excited state, requiring photosensitizers and
photons
Sources of oxygen free radicals
 In mitochondria:
- generation of energy - ATP
- glucose, fatty acids, amino acids
- O2 2H2O
4e-
- leakage of O2-. (superoxide)
H2O2 (hydrogen peroxide)
 Antioxidants

 Prevents the transfer of electron from O2

to organic molecules
 Stabilizes free radicals
 Terminates free radical reactions
Free Radical Defense System

 Antioxidant Enzymes
 Antioxidant Quenchers
 Antioxidant from
Foods – nutrients/non-
nutrients
 Antioxidant Enzymes
 Superoxide Dismutase (SOD) – to get rid
of superoxide produced from electron
transport chain, the product is hydrogen
peroxide.
 MnSOD (mitochondria).
 CuZn SOD (cytosol).
 Oxygen Radical Defense
Enzymes
GSH
CuZnSOD Peroxidase

O2•¯ H2O2 H2O + O2

Fe2+
Mn SOD Catalase

OH•
 Antioxidant Enzymes - 2

 Glutathione Peroxidase (GSH PX) – to

get rid of hydrogen peroxide (H2O2) and
some lipid peroxide. It requires reduced
glutathione (GSH) as substrate and
produces oxidized glutathione (GSSG)
as product. A cytosolic enzyme.
 Functions of GSH-dependent
Enzymes

L-OH
H 2O GSSG NADPH

GSH Px GSH--Rx
L-OOH NADP+
GSH
H 2O 2 X.
GSH-TR

GSX

X-Mercapturic Acid
 Glutathione
 GSH is a tripeptide, g-glutamyl-
cysteinyl-glycine
 The sulfur atom of the cysteine
moiety is the reactive site which
provides electrons
 GSH is stable because the g bond
in glutamyl-cysteine (not the a
peptide bond) is resistant to cellular
peptidases
 Glutathione
 GSH is the most abundant non-protein thiol in
mammalian cells
 GSH is a substrate for two enzymes that are
responsible for detoxification and
antioxidation.
 Other physiological roles including cysteine
storage and transport, prostaglandin
metabolism, immune function, cell
proliferation and redox balance
 Glutathione Synthesis
Protein
Methionine
Cysteine
Glutamate
g-Glutamylcysteine
Glycine
 Antioxidant Enzymes - 3

 Catalase –to get rid of hydrogen peroxide

produced in peroxisome.
 Antioxidants From Food
 Antioxidant nutrients – vitamin E, vitamin C,
(vitamin A?), beta-carotene
 Phytochemicals – antioxidants from plants