ANTIOXIDANTS : Reduce Risk of Many Disease

Antioxidants are molecules in your body which counter free radicles. Antioxidants have the ability to scavenge free radicals in the human body, and are suggested to contribute to the protective effect of plant-based food on diseases such as cardiovascular disease (CVD), cancer, and type 2 diabetes. However, evidence from supplementation studies that use different antioxidants, including vitamin C , vitamin E, carotenoids, zinc, or selenium, does not support the hypothesis that antioxidants reduce the risk of these diseases. Intervention studies highlight a lack of information on the safety of sustained intakes of moderate to high doses of micronutrient supplements and suggest that it is impossible to rule out long-term harm, especially in smokers. Thus a reduction agent can also be called an antioxidant. Antioxidants are regarded as important in the fight against the damage that free radicals produced due to oxidative stress can cause. Although the human body has its own defenses against oxidative stress, with age or disease these become weak. Antioxidants are either hydrophilic or hydrophobic. Water soluble or hydrophilic antioxidants are active in the blood plasma while the water insoluble antioxidants protect the cell membranes.

SIGNIFICATION OF ANTIOXIDANTS

Antioxidants have become scientifically interesting compounds due to their many benefits such as anti-aging and anti-inflammatory. Today, it is still used in many areas. In food technology, antioxidants are added to many foodstuffs in order to enrich the foods and eliminate the problems. Therefore, studies to determine the antioxidant activities of natural foods and their components are also continuing rapidly. Antioxidants have also been replaced in the encapsulation studies used for the preservation and stabilization of food components. Of course, preservation of foods is as important as their production. The latest packaging techniques for food preservation are edible films and coatings. The protective function of edible films and coatings can be improved by the addition of antioxidants. Unlike these, studies on plants and animals have been investigated in vivo in terms of how the antioxidant activity changes as a result of metabolic activities.

CLASSIFICATION OF ANTIOXIDANTS.
 

APPLICATION AND USE OF ANTIOXIDANTS.

Food antioxidant

eople in today's world want to eat healthier food to stay fit and this is being achieved by incorporating unsaturated and polyunsaturated fats in the food products being marketed. The quality of any product is measured on the scale of certain parameters and the approval of the same by its consumers. Similarly, in terms of food quality it is measured on parameters like aroma, taste and its appearance. As the human lifestyle and also its view towards food are changing thus there is an increased shift observed from convenient foods to ready-to-eat product category. For this there is need of certain potential health protecting factors named as Antioxidants.Antioxidants have wide application as these are used as additives in fats and oils and in food processing industries to prevent food spoilage. It is studied that spices and some herbs are good sources of many potential antioxidants. These are added to food which contain unsaturated fatty acids to make them last longer and to prevent them from turning rancid under oxidative stress. Thus, efforts are being made to reduce oxidation by increasing addition of antioxidants to food. Synthetic phenolic antioxidants (butylated hydroxyanisole [BHA], butylated hydroxytoluene [BHT], and propyl gallate) have inhibited action on oxidation; chelating agents, such as ethylene diamine tetra acetic acid (EDTA), bind metals and in this way reduce its metal participation in the reaction. Some vitamins (ascorbic acid [AA] and α-tocopherol), many herbs and spices (rosemary, thyme, oregano, sage, basil, pepper, clove, cinnamon, and nutmeg), and plant extracts (tea and grapeseed) contain antioxidant components thus imparting antioxidant properties to the compound.The natural phenolic antioxidants often act as reducing agents, terminate the free radical chain reaction by removing the same, absorb light in the ultraviolet (UV) region (100–400 nm), and chelate transition metals, thus inhibit oxidation reactions by itself being oxidized and also prevent the production of off-odours and tastes.

Although oxidation reactions are life crucial they can be damaging as well, thus it is very essential to maintain the complex system of multiple antioxidants nutritionally such as selenium, vitamin C and E which have significant immuno-stimulant, anti-inflammatory and anti-carcinogenic effects. In addition, they have a very important role in protecting the structural integrity of ischaemic or hypoxic tissues, and to some extent in anti-thrombotic actions too. Thus because of such diverse applications of antioxidants, their uses are being extensively studied in pharmacology, more specifically in the treatment for cancer, stroke, cardiovascular and neurodegenerative diseases and certain diabetic complications.



 

Role of antioxidants in diabetes

Diabetes is a major worldwide health problem. It is a chronic metabolic disorder characterized by absolute or relative deficiencies in insulin secretion or non-secretion of insulin resulting in chronic hyperglycaemia and disturbances of carbohydrate, lipid, and protein metabolism. As a consequence of the metabolic de-arrangements in diabetics, various complications develop including both macro- and micro-vascular dysfunctions.Various studies have shown that diabetes mellitus is associated with increased formation of free radicals and decreases antioxidant potential which, leads to disturbances in the balance between radical formation and protection against which ultimately results in oxidative damage of cell components such as proteins, lipids, and nucleic acids. An increased oxidative stress can be observed in both insulin dependent (type 1) and non-insulin-dependent diabetes (type 2).Among various factors that are responsible for increased oxidative stress, glucose autoxidation is most responsible for the production of free radicals. Other factors include cellular oxidation/reduction imbalances and reduction in antioxidant defences (including decreased cellular antioxidant levels and a reduction in the activity of enzymes that dispose of free radicals). In addition, increased levels of some prooxidants such as ferritin and homocysteine are also observed. Another important factor is the interaction of advanced glycation end products (AGEs) with specific cellular receptors called AGE receptors (RAGE).

It has been seen in individuals with higher levels of serum antioxidants, particularly serum tocopherol shows lower risk of type 2 diabetes mellitus. The primary defence against oxidative stress in the cell includes reduced glutathione (GSH), and glutathione peroxidase (GSH-Px). The most common antioxidant deficiencies reported in diabetes are lower levels of ascorbate, glutathione and superoxide dismutase. In diabetic neutrophils and monocytes lower concentrations of reduced glutathione have been documented. Plants particularly those with high levels and strong antioxidant compounds have an important role in improving the disorders involving oxidative stress such as diabetes mellitus. There are many investigations which have studied the effect of these plants and their antioxidant ingredients on diabetes and its complications and achieved good results showing that effects of plants with high levels of antioxidants in the management of diabetes mellitus.



 

Role in premature infants

Supplementing enzymatic and/or non-enzymatic antioxidants in infants could be beneficial in decreasing injury from excess production of ROS, particularly in disorders such as bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, and necrotizing enterocolits.



 

Enzymatic antioxidants

Enzymatic antioxidants are gestationally regulated, with decreased levels in premature newborns compared to full term neonates. ROS-induced injury could be reduced by overexpression of antioxidants as suggested by various models using transformed human alveolar epithelial cells. Increased expression of either MnSOD or CuZnSOD reverses the growth inhibitory effects of hyerpoxia in lung epithelial cells.21 Apart from reducing ROS production, overexpression of SOD also mitigated the activation of the JNK/AP1 pathway which has been implicated in ROS-induced mitochondrial injury and apoptotic cell death. Melatonin is a pineal hormone which exhibits an indirect antioxidant effect, by supporting SOD and glutathione peroxidase activity as well as direct effects, through lipid peroxidation and scavenging oxygen-induced ROS.

Non-enzymatic antioxidants

Resistance to oxidative stress also relies on non-enzymatic pathways as non-enzymatic antioxidants (NAC) get depleted in response to ROS-mediated stress. The effects of vitamin A are likely to mediate on retinol-binding protein and the retinoic acid receptor through its action. NAC is a precursor of the antioxidant glutathione and a large multicenter trial showed no reduction in survival or the incidence of BPD in 36 weeks CGA or improved pulmonary function at term. Ceruloplasmin, transferrin, and ferroxidase all aid in the metabolism of iron, which can act as a potent oxidizing agent. Diminished function or bioavailability of these proteins may predispose the preterm infant to increased production of ROS.





 

In the human body, oxidative damage caused by reactive oxygen and reactive nitrogen species such as hydroxyl radicals (OH−), peroxyl radicals (OOR−), superoxide anion (O2−), and peroxynitrite (ONOO−) is protected with the help of endogenous antioxidants. The endogenous antioxidative systems include enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, along with various non-enzymatic compounds such as selenium, α-tocopherol, and vitamin C.31 Apart from these, contribution of amino acids, peptides, and proteins also helps in overall antioxidative capacity of cells and towards maintaining the health of biological tissues. For example, blood proteins are estimated to scavenge 10–50% of the peroxyl radicals formed in the plasma. Peptides like carnosine, anserine, and glutathione are well-known for their endogenous antioxidative activity. However, with progression of age the antioxidant-prooxidant balance in human body changes along with other factors such as environmental pollutants, fatigue, excessive alcohol intake, and high fat diets. The plasma and cellular antioxidant potential as well as the absorption of nutrients, including antioxidants, gradually diminish with progressing age. Researches have also indicated an accumulation of protein carbonyls with the ageing process in humans as a result of the action of free radicals on the proteins.Use of dietary antioxidants has been recognized as potentially effective to promote human health by increasing the body's antioxidant load.

Dietary antioxidant supplements and functional foods containing antioxidants like α-tocopherol, vitamin C, or plant-derived phytochemicals such as lycopene, lutein, isoflavones, green tea extract, and grape seed extracts find a huge demand in the current marketplace.

Medical Application of Antioxidants

Antioxidants as anti-cancerous agents

Various research studies conducted so far have confirmed the role of antioxidants, viz., Lanthanides, selenium, flavonoids, lycopene and glutathione as anti-cancerous compounds in bio-coordination chemistry. Recent developments in medicine chemistry have become crucial for improving the design of the compound, reducing toxic side effects and understanding their mechanism of action. Numerous metal based drugs are widely used in the treatment of cancer. Lanthanides are also known as pharmacological agents in radioimmuno and Photodynamic therapy and are of specific interest due to its therapeutic radioisotopes nature. It has been reported that these Lanthanides are coordination compounds with improved pharmacological properties and a broader range of antitumour activity.

Flavonoids, low molecular weight polyphenols of plant origin are a group of naturally occurring compounds. These are widely distributed in the human food supply through fruits and vegetables and are considered to bear potential anticarcinogenic effects. These are believed to be good scavengers of free radicals. Around 28 naturally occurring and synthetic flavonoids have been suggested as novel anti leukamic compounds. Besides, flavonoids have also been reported to exert multiple biological effects including anti-inflammatory anti allergic, antiviral and anticancer activity.

Lycopene – It is widely accepted fact that diet changes are powerful tool for cancer prevention and inhibition of cancer progression. It has been found that lycopene can significantly reduce the risk of prostate cancer in men. Not only this, it is helpful in preventing cancer of pancreas, colon, rectum, oesophagus, oral cavity, large bowel, ovaries, cervice and mouth. Lycopenes have a specific role in preventing heart disease and protect the skin against sun damage.

Glutathione – A major intracellular antioxidant in the body is a tripeptide thiol compound. It has been reported that glutathione might be an effective treatment for hepatocellular carcinoma. In another study on rats it was found that oral administration of glutathione caused regression of liver tumours and increased the survival of tumour bearing animals.

Selenium, a mineral antioxidant is an important part of endogenous enzymes and an essential trace mineral present in the body. It is a natural antioxidant that defends the body against the free radicals. There are reports confirming the role of Selenium in the prevention of Cancer as well as in the control of Heart failure.

Antioxidants as hepatoprotective agents

Previous reports confirm that antioxidants have been religiously used in the treatment of various types of liver diseases. Several clinical trials have confirmed the effectiveness of antioxidants like Vitamin C, E, etc. in the treatment of hepatocellular carcinoma patients.

Antioxidant and Nervous system

The importance of the cerebellum is well known in controlling various motor activities in the body and the developing brain is susceptible to the detrimental effects of ROS. It has been reported that antioxidants prevent oxidative damage in cerebellar development and play an important role in general wellness as well as maintenance of wellness.46 Few antioxidants have been reported as therapeutic agents for acute central nervous injury.

Antioxidants and Red Blood cells

Erythrocytes transport oxygen and CO2 as their main function and repeatedly circulate through the lungs and capillaries during their 120-day life span. As these RBCs are continuously exposed to intracellular ROS derived from antioxidation of oxyhaemoglobin, there is a damage to these RBCs. In order to prevent this damage antioxidant enzymes are found in RBCs. Research has confirmed that CuZnSOD and catalase get accumulated at RBC membrane as first line of defence against oxidative stress. It was speculated that glutathione peroxidase cooperates with catalase to protect the whole RBCs (membrane and cytoplasm) from ROS damage.

Antioxidants and their therapeutic usage

Substantial consumption of antioxidants through fruits or vegetables, which are considered as good sources of antioxidants help in prevention of cardiovascular diseases. Antioxidants are also considered as possible treatments for Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and amylotrophic lateral sclerosis. Excessive oxidative damage to the cells leads to several pathological conditions such as rheumatoid, arthritis, cardiovascular disorders, ulcerogenesis and acquired immunodeficiency diseases. Antioxidants have been reported to play a specific role in the treatment of these diseases/disorders.

A vast number of studies have elucidated the role played by the antioxidants during oxidative stress leading to end number of health diseases, including leukaemia thalassaemia, ischemic stroke, hemodialysis, rheumatoid arthritis, critically ill patients, post menopause of women, schizophrenia and depression.There has been a significant importance of antioxidants in addressing the problem related to male infertility and efficacy and safety of antioxidant supplementation has confirmed in the medical treatment of idiopathic male infertility. In the last few years various antioxidants have been studied that prevent hyperoxaluria mediated Nephrolithiasis. It has been found that antioxidants have a great potential for treatment of Nephrolithiasis (Urinary tract stone disease). There are reports suggesting antioxidant supplement therapy as an adjuvant therapy is useful in patients with stress induced psychiatric disorders and generalized anxiety disorders.

Plants as a potential source of antioxidants

Synthetic and natural food antioxidants are used routinely in foods and medicine especially those containing oils and fats to protect the food against oxidation. There are a number of synthetic phenolic antioxidants such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) which have been widely used as antioxidants in the food industry, cosmetics, and the therapeutic industry. However, due to their high volatility, instability at elevated temperature, strict legislation on the use of synthetic food additives, the carcinogenic nature of synthetic antioxidants, and consumer preferences have led to shift in the attention of manufacturers from synthetic to natural antioxidants. In view of increasing risk factors of human to various deadly diseases, there has been a global trend toward the use of natural substance present in medicinal plants and dietary plants as therapeutic antioxidant. Various herbs and spices have been reported to exhibit antioxidant activity, including Eugenia caryophyllus, Piper brachystachyum, Elettaria cardamomum, Terminalia bellerica and Zingiber officinale.

Preeti Shrivastava

Foundation in Science