Antioxidants and their therapeutic implications

Although oxygen is essential for life, excess oxygen can have harmful effects. When oxygen is metabolised by the body it creates substances called free radicals which cause damage to our cells.

Free radicals can also be created by exposure to pollution, cigarette smoke and fatty foods.

Excessive amounts of free radicals are thought to be related to the development of conditions such as:-

Heart and liver disease Some cancers, Arthritis, Accelerated ageing Eyesight deterioration.

The body has its own natural defences against free radicals, but these systems can sometimes be overwhelmed.

Antioxidants are naturally occurring nutrients in food or chemical compounds which help destroy free radicals and minimise damage to our cells. they can delay the start or slow the rate of lipid per oxidation reaction in food systems.

SOURCES OF ANTIOXIDANTS

VITAMIN-E VITAMIN-CBETA-CAROTENESELENIUMPHYTONUTRIENTS

Vitamin E It is one of the strongest antioxidants,

and can be found in nuts, oils, green vegetable and wholegrain. It helps prevent disease by destroying free radicals and protecting DNA in cells from damage.

Vitamin C It has a dual role, in that it helps the body absorb

vitamin E and protects it from harm. Citrus fruits and vegetables are the best food sources of vitamin C. Smokers in particular should ensure they get enough vitamin C, as it helps fight toxins and free radicals from cigarette smoke.

Beta-carotene It is converted by the body into

vitamin A. It benefits skin and hair, helps maintain strong bones and protects against eye problems. Beta-carotene is found mainly in red- and orange-coloured fruits and vegetable.

Selenium

It is the main mineral antioxidant. It is involved in the production of powerful enzymes which ‘mop up’ free radicals and deactivate them. Selenium is found in brazil nuts, seafood and red meat.

Phytonutrients They are naturally occurring plant chemicals

which don’t have any nutritional value, but which have the ability to act as antioxidants. Different types of phytochemical occur in different foods: flavonoids are found in abundance in fruit, vegetables, dark chocolate and red wine (which should be consumed in moderation); tea and grapes are a good source of polyphenols; allium sulphur compounds are found in onions, leeks and garlic.

lipid per oxidation:

Lipid per oxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes are formed resulting in cell damage.

Mechanism of lipid per oxidation

PROCESS INVOLVED IN THE MECHANISM OF LIPID PER OXIDATION

Initiation: Initiation is the step in which a fatty acid radical is produced. The most notable initiators in living cells are reactive oxygen species(ROS), such as OH· and HO2, which combines with a hydrogen atom to make water and a fatty acid radical.

Propagation: The fatty acid radical is not a very stable molecule, so it reacts readily with molecular oxygen, thereby creating a peroxyl fatty acid radical. This too is an unstable species that reacts with another free fatty acid, producing a different fatty acid radical and a lipid peroxide.

Termination: When a radical reacts with a non-radical, it always produces another radical, which is why the process is called a "chain reaction mechanism." The radical reaction stops when two radicals react and produce a non-radical species.  Living organisms have evolved different molecules that speed up termination by catching free radicals and, therefore, protecting the cell membrane. One important such antioxidant is vitamin E. Other anti-oxidants made within the body include the enzymes superoxide dismutase, catalase, and peroxidase.

EFFECTS OF LIPID PER OXIDATION:

Flavour Quality Loss: Rancid flavour Changes of colour and texture Consumer Acceptance Economic loss

Nutritional Quality Loss: Essential Fatty Acids Vitamins

Health Risks: Toxic Compounds Growth Retardation Heart Diseases

Ideal Antioxidants

No harmful physiological effects

Not contribute an objectionable flavor, odor,

or color to the fat

Effective in low concentration

Fat-soluble

Carry-through effect No destruction during

processing

Readily-available

Economical

Not absorbable by the body

Kinds of Antioxidants

Natural antioxidants: Tocopherols Nordihydroguaretic Acid (NDGA) Sesamol Gossypol

Synthetic antioxidants: Butylated Hydroxy Anisole (BHA) Butylated Hydroxy Toluene (BHT) Propyl Gallate (PG) Tertiary Butyl Hydroquinone (TBHQ)

Therapeutic implications of antioxidants

Antioxidant in cardiovascular diseaseAntioxidant therapy in cancerAntioxidants in Brain injury: Antioxidants in stroke treatment :Antioxidants in neurodegenerative diseasesAntioxidants in apoptosisAntioxidants in liver damage

Antioxidant therapy in cardiovascular disease

Antioxidant therapy may inhibit atherosclerosis and thereby prevent the clinical complications of the disease such as CAD, and in particular, MI.

Free radicals are formed by several exogenous processes such as radiation and tobacco smoke, and are the endogenous natural by-products of cellular metabolism. these radicals tend to damage protein, DNA, lipids and carbohydrates as result cell death.

Antioxidant therapy in cancer

The following is a list of common antioxidants used in cancer programs.

Beta caroteneVitamin CVitamin ESeleniumLipoic acidPoly MVA

Beta carotene

Beta-carotene is a form of vitamin A. Vitamin A is a strong immune booster. It stimulates the activity of immune cells against tumor cells. Has been shown to inhibit the promotion of caner, while beta carotene (precursor to vitamin A) inhibits the initiation of cancer. Beta-carotene can decrease the amount of damage free radicals do to a cell's DNA. Such DNA damage is thought to be one mechanism that causes cancer, and indeed, some early studies suggested that beta-carotene might reduce the risk of cancer.

Vitamin C

  It is known that vitamin C acts as an antioxidant and free radical scavenger that reacts directly with super oxide, hydroxyl radicals, and singlet oxygen produced during normal cellular metabolism. Oxygen is necessary for life. Oxygen also comes in several radical forms that have been implicated in both initiation and post initiation stages of the carcinogenic process as well as in invasion and metastatic processes. Aside from its antioxidant properties, there is no single universal accepted and proven explanation for vitamin C's cancer fighting properties.

Vitamin E

Vitamin E is an important fat-soluble antioxidant, vitamin E's preventive role in cancer has been well proven.

Highly malignant melanoma cell in vitro has been shown to be converted into differentiated (normal) cell after 3 days of exposure to Vitamin E succinate.  

Ovarian and cervical cancer - vitamin E slow downs the mitotic activity of cancer cell but normal cell don't get affected.  

Glioma tumor cells (present in the brain) are also more effective attacked by vitamin E succinate, probably because of its better penetration of blood bran barrier.

Vitamin E succinate enhances radiation in cancer cell and protects the normal cell.

SeleniumIt is a powerful antioxidant with a central role in

the protection of tissues from the damaging effects of oxygen free radicals. The use of selenium compounds as a cancer treatment predates most conventional treatments currently in use. 

200 mcg of selenium a day has been shown to reduce cancer death by 50% and prostate cancer by 62% after 4 years. Cancer patients are often found to be deficient in selenium. Selenium works synergistically with vitamin E. 

 Lipoic acid

It is called the universal antioxidant for its ability to dissolve well in water and in fat environment, Lipoic acid increase the effectiveness or potency in other antioxidants. It can cross the blood brain barrier while others cannot .One of the most beneficial effects of alpha Lipoic acid is its ability to regenerate other essential antioxidants such as vitamins C and E, coenzyme, and glutathione. 

Poly MVA This is an alpha Lipoic acid complex with

palladium. It is a non-toxic polynucleotide reductase

named POLYDOX (USA trials), Poly-MVA

(Canada and Mexico) or LAPd by some

researchers. The element platinum is very lethal to cancer cells,

but also very toxic to humans.  It's close relative: palladium, however, is nontoxic in

its present form.  The MVA stands for minerals, vitamins, and amino

acids. LAPd stands for Lipoic acid/Palladium

complex.

Antioxidants in Brain injury:

Antioxidants are commonly used as medications to treat various forms of brain injury. Here, superoxide dismutase mimetics,

sodium thiopental and propofol are used to treat reperfusion injury and traumatic brain injury.

Antioxidants in stroke treatment :

Experimental drug NXY-059 and ebselen are being applied in the treatment of stroke.

Antioxidants in neurodegenerative diseases

Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease , Parkinson's disease, and amyotrophic lateral sclerosis.

Others:These compounds appear to prevent

oxidative stress in neurons and prevent apoptosis and neurological damage.

They may prevent damage to the liver caused by excessive alcohol.

Submitted By:

Manish KumarM.Pharm PharmacologyMangalayatan university

Thank you

Click icon to add picture