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ORIGINAL CONTRIBUTION |
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| Year : 1997 | Volume
: 51
| Issue : 7 | Page : 226-230 |
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Oxidants, antioxidants and diseases - A brief review
K Singh
Department of Physiology, Pt. B.D. Sharma PGIMS, Haryana, India
Correspondence Address:
K Singh
Department of Physiology, Pt. B.D. Sharma PGIMS, Haryana
India
PMID: 9401231
How to cite this article:
Singh K. Oxidants, antioxidants and diseases - A brief review. Indian J Med Sci 1997;51:226-30 |
Reactive metabolites [oxygen free radicals/reactive oxygen species (ROS)] of oxygen are generated as an integral part of our daily life. A free radical is either an atom or molecule containing one or more unpaired electrons and capable of existing indeperidently. This characteristic makes it more reactive than nonradical and thus are implicated in pathogenesis of atherosclerosis, cancer, neurodegenerative and inflammatory diseases. Oxygen radicals and their by products that are capable of inciting oxidative tissue damage. ROS and O 2 radicals are not synonymous. ROS include superoxide anion (0 2 -) hydroxyl radical (HO), hydrogen peroxide (H 2 O 2 ), singlet oxygen (10 2 ), hydroperoxides and epoxides. Increased free radical formation in body is known as oxidative stress. It refers to disturbance in the pro and antioxidant balance in favour of proxidant. [1] HO is most reactive and aggressive of various ROS and capable of initiating deleterious reactions i.e. lipid peroxidation and DNA damage.
Sources of ROS : Sources of ROS are given in [Table 1].
Antioxidant Protection : To protect against free radical induced damage, a number of defence mechanism exists in the body. Antioxidants (AOS) are compounds which scavenge free radicals.
Endogenous Antioxidants : Endogenous AOS are intracellular (I/C) essential enzymes i.e. superoxide dismutase (SDD), catalase, glutathione peroxide. [2] The enzyme SOD dismutates two molecules of 0 2 --perreaction cycle with formation of [Additional file 1]
Exogenous Antioxidants : Predominant dietary AOS are a tocopherol. (AT) (vit. E), ascorbic acid (AA) (Vit. C), betacarotene (BC), retinoic acid (vit. A), flavanoids. Presence of significant amount of antioxidants account for some of the beneficial effects of fruits, grains and vegetables. [5]
α tocopherol : It is lipid soluble and functions as most important lipid peroxidation chain breaking ADS in tissues and plasma and as a cell membrane stabilizer.
Vitamin C : It is water soluble. It reacts and scavenges a wide varie.y of ROS including 0 2 -, OH-, various lipid hydroperoxides. However, one feature of this AO that demand special attention is that in presence of Fe 3 + orCu 2 + excess (∫1 mM) , vit. C may act as a strong prooxidant and may actually induce lipid peroxidation and oxidative modification of genomic structure [1] . Under such condition vit. C may reduce Fe 3 + and Fe 2 + with generation of OH.
Carotenoids : Carotinoids are B carotene and lycopene. Under partial pressure of 0 2 below 150 Torr, B carotene is a very efficient free radical scavenger particularly 0 2 --. However, at higher 0 2 pressure it exhibits autocatalytic prooxidant properties. [6]
Dietary antioxidant flavonoids Flavonoids are polyphenolic dietary substances that occur in plants (predominantly in leaves). They act as superoxide scavengers, A0 and also inhibit oxidation and cytotoxicity of LDL. Main sources of flavonoids are tea, red wine, onion and apple. They are present in significant amount in pumpkin, guava, garlic and spices i.e. cloves, cardamom, asafoetida, coriander and black pepper. They play critical roles in maintenance of health and prevention of diseases. [7]
Antioxidant chain reaction Various endo and exogenous AOS are known to act in concert as an antioxidant chain reaction. [1] Reduced glutathione, apart from contributing to enzymatic and nonenzymatic decomposition of ROS, plays a central role in coordinating the activities of crucial exogenous antioxidants. This synergism should be considered with particular care when designing antooxidant therapy protocols. [1]
Oxidative damage : HO can damage cellular membrane and lipoproteins by lipid peroxidation. Damage to protein by ROS leads structural changes and loss of enzymatic activity and the damage to DNA is mutagenic. These oxidative DNA damage and mutation accumulate with age and may contribute to carcinogenesis and other degenerative diseases. [2]
Intracellular changes following oxidative stress : Although it is not very clear, oxidative stress induced cytotoxic effects appear to be mediated by perturbation of I/C free calcium (Ca 2 +) and thiol homeostasis. [9]
Role of antioxidants
AOS and exercise : Exercise induced oxidative stress has been shown to be implicated in muscular dystrophy and early onset of oixdative muscle fatigue. It is shown that endurance training is capable of boosting physiological ADS defence capacity [9] through glutathione dependent ADS mechanism. Marked increase in oxidised glutathio-ne (GSSG), that is cytotoxic,, may be used as an indicator of oxidative stress of exercise. [1]
ADS and cardiovascular diseases : To prevent oxidation, which contribute to formation of atherogenic fatty streak in arterial wall, LDL (low density lipoprotein) contains various AD molecules i.e. AT (predominant) and BC. AA in plasma also prevents LDL from getting oxidised. [2] Probucol, a synthetic AO, useful in coronary heart disease and reduces kanthromata in familial hypercholemia. [10] Prottective role of AOS in myocardium stunning, heart surgery, ischaemia repurfusion injury and during transplantation is well established. [11] Salicylates i.e. aspirin may also have AO properties. [12] Several studies have indicated a low level in plasma and low dietary intake of vit. C with high blood pressure. [12]
AOS and central nervous system (CNS) : Due to high 0 2 consumption, low AO defense status, high lavels of free iron and oxidizable substances i.e. polyunsaturated fatty acids and catechala mines make CNS more susceptible to oxidative stress. It is propounded to play role in genesis of Parkinson's disease (PD) and Alzheimer's disease (AD).
AOS and Diabetes (Mellitus : Diabetic patients have been found to have higher levels of oxidative stress indices. Glycwion reactions are believed to be responsible for most of the diabetic complications. [1]
AOS and Renal diseases : Free radical injury and oxidative stress have been implicated in many renal diseases i.e. ARF, IgA nephropathy, anaemia of CRF and ischaemic kidney preserved for transplantation. [12]
AOS and Respiratory diseases ARDS, ventilation lung asthma and sarcoidosis are some of the diseases associated with free radical toxicity in man. Salanium and vit. E reduce respiratory burst response (RBR) in neutrophils of smokers. [12]
AOS and Diseases of Liver and GIT : AO therapy in inflammatory bowel disease (IBD) i.e. ulcerative colitis and Crohn's disease, appears to reduce relapse rates. Low AO levels have been reported in cholelithiasis, viral hepatitis B and Wilson's disease, secondary to the disease process. [12]
AOS and Rheumatoid Arthritis
Xathine dehydrogenase located in endothelium of symposium is responsible for generation of ROS i.e. 0 2 '-- and thus production of Rheumatoid factor. [1]
AOS and cancer : Thioll antioxidant i.e. N-acetyl cysteine (NAC) has been found to be effective in chemcprevention of mutation and cancers. [13]
AOS and AIDS: HIV infected paren.s have decreased I/C GSH level in their circulating T cells. Thiol AO NAC was found to be effective in anti HIV therapy. [14]
AOS in malaria : Serum retinol levels were found to be depressed in severe falciparum malaria. [12]
AOS and Eye disease : Bunce et al in 1990 have shown in an animal model that oxidative mechanism is responsiblee for development of cataract. [15]
AOS and aging : Free radical theory of aging has gained remarkable momentum in recent past. Simultaneous over expression of copper-zinc superoxide dismutase and catalase decrease protein oxidative damage and increase life span.
| ¤ Summary | |  |
Although oxygen (0 2 ) is needed to the body, partially reduced forms of 0 2 and some of their derivatives collectively called reactive oxygen species (ROS), are highly toxic prooxidants to the body. To prevent ROS toxicity body's endogenous and exogenous antioxidants (AOS) act in concert. To maintain health a balance between pro and anti oxidants is very necessary.
| ¤ References | | |
| 1. | Sen CK. Oxygen toxicity and antioxidants : State of the art. IJPP 1995;39:177-196.  |
| 2. | Frei B. Reactive oxygen species and antioxidant vitamins : mechanism of action. Am J Med 1994;97 (Supple 3A) (5s-13s). |
| 3. | Keher JP, Smith CV. Free radicals in biology : sources, reactivities and roles in the etiology of human diseases. In Frei Bed. Natural antioxidants in human health and disease. Orlando FL: Academic Press 1994: 25-62. |
| 4. | Arduini A, Eddy L, Hochstein P. Detection of ferryl myoglobin in the isolated ischaemic rat heart. Free Rad Biol Med 1990;9:511-513. [PUBMED] [FULLTEXT] |
| 5. | Halliwell B. Free radicals, antioxidants and human disease. Curosity, cause of consequence. Lancet 1994;344:721-4. |
| 6. | Burton BW, Ingold KV. b cartene is an unusual type of lipid antioxidant. Science Washington DC 1984; 224:569-573. |
| 7. | Nair S, Gupta R. Dietary antioxidant flavonoids and coronary heart disease. JAPI 1996;44:699-702. [PUBMED] [FULLTEXT] |
| 8. | Reed DJ. Status of calcium and thiols hepato-cellular injury by oxidative stress. Semin Liver Dis 1990;10:285-292. [PUBMED] [FULLTEXT] |
| 9. | Sen CK, Hanninen O. Physiological antioxidants. In : Sen CK, Packer L, Hanninen 0, eds. Exercise and oxygen toxicity. Amsterdam, Elseveir Science Publishers B.V. 1994; 89-126. |
| 10. | Steinberg D. Antioxidants and atherosclerosis : a current assessment. Circ 1991;84:1420-25. |
| 11. | Das DK, Maulik N. Protection against free radical injury in the heart and cardiac perfarmance. In: Sen CK, Pocker L, Hanninan 0, eds, Exercise and oxygen toxicity. Amsterdam, Elsevier Publishers B. V. 1994:359-388. |
| 12. | DeFlor S, D Agestini F. Cesarone CF. Antioxidant activity and other mechanisms of thiols involved in Chemoprevention of mutation and cancer. Am J Med 1991;91:3C-1225-1305. |
| 13. | Roederer M, Ela SW, Staal FJT, Herzenberg LA, Herzenberg LA. N-acetylcystone : a new approach to anti HIV therapy. AIDS Res Hum Retrow 1992;8:209-217. |
| 14. | Bunce GE, Kinoshita J, Horwitz J. Nutritional factor in cataract. Ann Rev Nutr 1990;10:233-254. |
| 15. | Orr WC, Sohal RS. Extension of life span by over-expression of superoxide dismutes and catalase in Drosophila melanogaster. Science 1994;263:1128-1130. [PUBMED] [FULLTEXT] |
[Table 1]
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