Mechanisms of Antioxidant Actions and their Role in many Human Diseases: A Review


1 Department of Biology, Faculty of Science, University of Kufa, Najaf, Iraq

2 Department of Biology, College of Science, University of Misan, Maysan, Iraq

3 AL Sader Teaching Hospital, Maysan Health Directorate, Ministry of Health, Maysan, Iraq

4 Department of Mechanical and Aerospace Engineering, Monash University, VIC 3800, Australia



Antioxidants are substances that are available in various natural food products, which play a vital role in reducing body cell damage caused by free radical formation. An imbalance between antioxidants and free radicals contributes to an oxidative stress in the human body. The electron acceptability of O2 produced Reactive Oxygen Species (ROS). The imbalance equilibrium between the production of reactive oxygen species (ROS) and the purification supports a rise in the ROS levels, which is the key cause of disrupted cellular activity. A recent review of excessively mild antioxidants, processes of movement, and their role in many human illnesses.   


1. Davari A., Solouki M., Fazeli-Nasab B., 2018. Effects of jasmonic acid and titanium dioxide nanoparticles on process of changes of phytochemical and antioxidant in genotypes of Satureja hortensis L. Eco-Phytochemical Journal of Medicinal Plants. 5(4), 1-20 [In Persian].
2. Baineni R., Gulati R., Delhi CK., 2017. Vitamin A toxicity presenting as bone pain. Archives of Disease in Childhood. 1;102(6), 556-8.
3. Speakman J.R. 2003. Oxidative phosphorylation, mitochondrial proton cycling, free-radical production, and aging. Advances in Cell Aging and Gerontology. 1; 14, 35-68. 
4. PhD OI. 1999. Free radicals, antioxidants, and international nutrition. Asia Pacific Journal of clinical nutrition.8(1), 53-63.
5. Gruhlke M.C., Slusarenko A.J. 2012.The biology of reactive sulfur species (RSS). Plant Physiology and Biochemistry. 1; 59, 98-107.
6. Halliwell B., 2006. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiology. 1;141(2), 312-22.
7. Herbert V., 2001. 21 Vitamin, Mineral, Antioxidant, and Herbal Supplements: Facts and Fictions. Behavioral Neurology in the Elderly.  23-27.
8. Kimura H., Nagai Y., Umemura K., Kimura Y., 2005. Physiological roles of hydrogen sulfide: synaptic modulation, neuroprotection, and smooth muscle relaxation. Antioxidants & Redox Signaling. 1;7(5-6), 795-803.
9. Liu D., Jin H., Tang C., Du J., 2010. Sulfur dioxide: a novel gaseous signal in the regulation of cardiovascular functions. Mini Reviews in Medicinal Chemistry. 1;10(11), 1039-45.
10. Calabrese V., Cornelius C., Mancuso C., Pennisi G., Calafato S., Bellia F., Bates T.E., Stella A.M., Schapira T., Kostova A.T., Rizzarelli E., 2008. Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochemical Research. 1;33(12), 2444-71.
11. Na H.K., Surh Y.J., 2008. Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green
tea polyphenol EGCG. Food and Chemical Toxicology. 1;46(4), 1271-8.
12. Tuzcu M., Sahin N., Karatepe M., Cikim G., Kilinc U., Sahin K., 2008. Epigallocatechin-3-gallate supplementation can improve antioxidant status in stressed quail. British Poultry Science. 1;49(5), 643-8.
13. Azab A.E., Albasha M.O., 2018. Hepatoprotective effect of some medicinal plants and herbs against hepatic disorders induced by hepatotoxic agents. J Biotechnol Bioeng. 2(1), 8-23.
14. Langseth L., 1996. Oxidants, antioxidants and disease prevention. ILSI. 16, 840–841. 
15. Young I.S., Woodside J.V., 2001. Antioxidants in health and disease. Journal of Clinical Pathology. 1;54(3), 176-86.
16. Halliwell B., 2007. Biochemistry of oxidative stress. Biochem Soc Trans. 35, 1147-1150.
17. Pacher P., Beckman J.S., Liaudet L., 2007. Nitric oxide and peroxynitrite in health and disease. Physiological Reviews. 87(1), 315-424.
18. Hagr T.E., Adam I.A., Mohammed E.H., El mageed M.A., 2021. GC/MS Analysis and Antioxidant Activity of Fixed Oil from Sudanese Safflower (Carthamus tinctorius L) Seeds. International Journal of Advanced Biological and Biomedical Research. 9(2), 138-146.
19. Willcox J.K., Ash S.L., Catignani G.L., 2004. Antioxidants and prevention of chronic disease. Critical Reviews in Food Science and Nutrition. 1;44(4), 275-95.
20. Gupta R.K., Singh N.,  2013. Morinda citrifolia (Noni) alters oxidative stress marker and antioxidant activity in cervical cancer cell lines. Asian Pac J Cancer Prev. 1;14(8), 4603-6.
21. Donaldson M.S., 2004. Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutrition Journal. 1;3(1), 19.
22. Cheung C.C., Zheng G.J., Li A.M., Richardson B.J., Lam P.K., 2001. Relationships between tissue concentrations of polycyclic aromatic hydrocarbons and antioxidative responses of marine mussels, Perna viridis. Aquatic Toxicology. 1;52(3-4), 189-203.
23. Tappel M.E., Chaudiere J., Tappel A.L. 1982. Glutathione peroxidase activities of animal tissues. Comparative Biochemistry and Physiology Part B: Comparative Biochemistry. 1;73(4), 945-9.
24. McCord J.M., Fridovich I., 1969. Superoxide dismutase an enzymic function for erythrocuprein (hemocuprein). Journal of Biological Chemistry. 25;244(22), 6049-55.
25. Hayes J.D., Pulford D.J., 1995. The glut athione S-transferase supergene family: regulation of GST and the contribution of the lsoenzymes to cancer chemoprotection and drug resistance part I. Critical Reviews in Biochemistry and Molecular Biology. 1;30(6), 445-520.
26. Mannervik B., Helena Danielson U., Ketterer B., 1988. Glutathione transferases—the structure and catalytic activity. Critical Reviews in Biochemistry. 1;23(3), 283-337.
27.25. Pickett C.B., Lu A.Y., 1989. Glutathione S-transferases: gene structure, regulation, and biological function. Annual review of Biochemistry. 58(1), 743-64.
28. Hayes P.C., Bouchier I.A., Beckett G.J., 1991. Glutathione S-transferase in humans in health and disease. Gut. 32(7), 813.
29. Pigeolet E., Corbisier P., Houbion A., Lambert D., Michiels C., Raes M., Zachary M.D., Remacle J., 1990. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mechanisms of Aging and Development. 15;51(3), 283-97.
30. Prohaska J.R., 1991. Changes in Cu, Zn-superoxide dismutase, cytochrome c oxidase, glutathione peroxidase, and glutathione transferase activities in copper-deficient mice and rats. The Journal of Nutrition. 1;121(3), 355-63.
31. Zelko I.N., Mariani T.J., Folz R.J. 2002. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radical Biology and Medicine. 1;33(3), 337-49.
32. Mosialou E., Ekström G., Adang A.E., Morgenstern R., 1993. Evidence that rat liver microsomal glutathione transferase is responsible for glutathione-dependent protection against lipid peroxidation. Biochemical Pharmacology. 22;45(8), 1645-51.
33. Nozik-Grayck E., Suliman H.B., Piantadosi C.A., 2005. Extracellular superoxide dismutase. The International Journal of Biochemistry & Cell Biology. 1;37(12), 2466-71. .Berg J.M., Tymoczko J.L., Stryer L., Clarke N.D., 2002. DNA replication, recombination, and repair. Biochemistry. 5th edition. New York, WH Freeman & Co. pp1119-1120.
35. Kirkman H.N., Galiano S., Gaetani G.F., 1987. The function of catalase-bound NADPH. Journal of Biological Chemistry. 15;262(2), 660-6.
36. Sharma R., Yang Y., Sharma A., Awasthi S., Awasthi Y.C., 2004. Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxidants and Redox Signaling. 1;6(2), pp 289-300.
37. Mosialou E., Ekström G., Adang A.E., Morgenstern R., 1993. Evidence that rat liver microsomal glutathione transferase is responsible for glutathione-dependent protection against lipid peroxidation. Biochemical Pharmacology. 22;45(8), pp 1645-51.
38.36. Ulusu N.N., Tandoğan B., 2007. Purification and kinetic properties of glutathione reductase from bovine liver. Molecular and cellular biochemistry. 1;303(1-2), 45-51.
39. Babich H., Gold T., Gold R., 2005. Mediation of the in vitro cytotoxicity of green and black tea polyphenols by cobalt chloride. Toxicology Letters. 15;155(1), 195-205.
40. Linster C.L., Van Schaftingen E., 2007. Vitamin c. The FEBS Journal. 1;274(1), 1-22.
41. Abd El-Hameid A.R., 2021. In vitro Callus Induction of Tomato and Evaluation of Antioxidant Activity of Aqueous Extracts and Enzymatic Activities in Callus Cultures. International Journal of Advanced Biological and Biomedical Research. 9(1), 9-19.
42. Duarte T.L., Lunec J.,  2005. When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C. Free Radical Research. 39(7), 671-86.
43.40. Matito C., Mastorakou F., Centelles J.J., Torres J.L., Cascante M., 2003. Antiproliferative effect of antioxidant polyphenols from grape in murine Hepa-1c1c7. European Journal of Nutrition. 1;42(1), 43-9.
44. Harborne J.B., Williams C.A., 2000. Advances in flavonoid research since 1992. Phytochemistry. 1;55(6), 481-504.
45. Vaya J., Mahmood S., Goldblum A., Aviram M., Volkova N., Shaalan A., Musa R., Tamir S., 2003. Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy. Phytochemistry. 1;62(1), 89-99.
46. Fetouh F.A., Azab A.E., 2014. Ameliorating effects of curcumin and propolis against the reproductive toxicity of gentamicin in adult male guinea pigs: Quantitative analysis and morphological study. American Journal of Life Sciences. 30;2(3), 138-49.
47. Mehta M., Kant V., Varshneya C., 2013. Screening of in vitro antioxidant potential of seabuckthorn seedcake extracts. Journal of Complementary Medicine Research. 2(2), 99-104.
48. Azab A.E., Albasha M.O., Elsayed A.S., 2017. Prevention of nephropathy by some natural sources of antioxidants. Yangtze Medicine. 13;1(04), 235.
49.46. Cyril D.G., Landry K.S., Francois K.Y., Abou B., Felix Y.H., Timothee O.A., 2016. Evaluation of nephroprotective activity of aqueous and hydroethanolic extracts of Trema guineensis leaves (Ulmaceae) against gentamicin-induced nephrotoxicity in rats. International Journal of Biochemistry Research & Review. 15(2), 1-10.
50. Ohlsson T., Bengtsson N., 2002. editors. Minimal processing technologies in the food industries. Elsevier; p. 85.
51. Gey K.F., Puska P., Jordan P., Moser U.K., 1991. Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. The American Journal of Clinical Nutrition. 1;53(1), 326S-34S.
52. Gey K.F., 1990. The antioxidant hypothesis of cardiovascular disease: epidemiology and mechanisms. Biochemical Society Transaction. 18(6), 1041-1045.
53. Liyana-Pathirana C.M., Shahidi F., Alasalvar C., 2006. Antioxidant activity of cherry laurel fruit (Laurocerasus officinalis Roem.) and its concentrated juice. Food Chemistry. 1;99(1), 121-8.
54. Fazeli-nasab B., Moshtaghi N., Forouzandeh M., 2019. Effect of Solvent Extraction on Phenol, Flavonoids and Antioxidant Activity of some Iranian Native Herbs. Scientific Journal of Ilam University of Medical Sciences. 27(3), 14-26.
55. Dembinska-Kiec A., Mykkänen O., Kiec-Wilk B., Mykkänen H., 2008. Antioxidant phytochemicals against type 2 diabetes. British Journal of Nutrition. 99(E-S1), ES109-17.
56. Sin H.P., Liu D.T., Lam D.S., 2013. Lifestyle modification, nutritional and vitamins supplements for age‐related macular degeneration. Acta Ophthalmologica. 91(1), 6-11.
57. Kalcher K., Svancara I., Buzuk M., Vytras K., Walcarius A., 2009. Electrochemical sensors and biosensors based on heterogeneous carbon materials. Monatshefte für Chemie-Chemical Monthly. 1;140(8), 861-89.
58. Abdel-Wahhab D., Hassan M.A., Bakeer R.M., Mohammed H.E., 2020. Chemical composition, antioxidant activity and preventive role of milk by-products against nicotine-induced alteration in sexual hormones and organs pathology in rats. Egyptian Journal of Chemistry. (Articles in Press)
59. Surai P.F., 2007. Natural antioxidants in poultry nutrition: new developments. In Proceedings of the 16th European symposium on poultry nutrition. World Poultry Science Association. 26-30.
60. Fazeli-Nasab B., Jafarvand N., Fooladvand Z., presented in part at the Internation Conference on Sustainable Development, Strategies and Challenges with a Focuse on Agriculture, Natural resources, Environment and tourism, tabriz, Iran, doi: 10.13140/RG.2.1.2876.2084, 2015.
61. Milner J.A., 1994. Reducing the risk of cancer. In Functional foods. Springer, Boston. pp. 39-70
62. Omenn G.S., Goodman G., Thornquist M., Grizzle J., Rosenstock L., Barnhart S., Balmes J., Cherniack M.G., Cullen M.R., Glass A., Keogh J., 1994. The β-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high-risk populations: smokers and asbestos-exposed workers. Cancer Research. 1;54(7 Supplement), 2038s-43s.
63. Jaichander P., Selvarajan K., Garelnabi M., Parthasarathy S., 2008. Induction of paraoxonase 1 and apolipoprotein AI gene expression by aspirin. Journal of lipid research. 1;49(10), 2142-8.
64. Glenville M., 2006. Nutritional supplements in pregnancy: commercial push or evidence based? Current Opinion in Obstetrics and Gynecology. 1;18(6), 642-7.
65. Kontush A., Mann U., Arlt S., Ujeyl A., Lührs C., Müller-Thomsen T., Beisiegel U., 2001. Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer’s disease. Free Radical Biology and Medicine. 1;31(3), 345-54.
66. Haider B.A., Bhutta Z.A., 2017. Multiple‐micronutrient supplementation for women during pregnancy. Cochrane Database of Systematic Reviews. (4), 1-5.
67. Anwar F., Latif S., Ashraf M., Gilani A.H. 2007. Moringa oleifera: a food plant with multiple medicinal uses. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 21(1), 17-25.
68. Losso J.N., 2003. Targeting excessive angiogenesis with functional foods and nutraceuticals. Trends in Food Science & Technology. 1;14(11), 455-68.
69. Ting H.H., Timimi F.K., Haley E.A., Roddy M.A., Ganz P., Creager M.A., 1997. Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation. 17;95(12), 17-22.
70. Grill V., Björklund A., 2000. Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities. Cellular and Molecular Life Sciences CMLS. 1;57(3), 429-40.
71. Bonnefont-Rousselot D., Bastard J.P., Jaudon M.C., Delattre J., 2000. Consequences of the diabetic status on the oxidant/antioxidant balance. Diabetes and Metabolism. 1;26(3), 163-77.
72. West I.C., 2000. Radicals and oxidative stress in diabetes. Diabetic Medicine. 17(3), 171-80.
73. Reaven P., 1995, Dietary and pharmacologic regimens to reduce lipid peroxidation in non-insulin-dependent diabetes mellitus. The American Journal of Clinical Nutrition. 1;62(6), 1483S-9S.
74. Liao J.K., Shin W.S., Lee W.Y., Clark S.L., 1995. Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. Journal of Biological Chemistry. 6;270(1), 319-24.
75. Kawano H., Motoyama T., Hirashima O., Hirai N., Miyao Y., Sakamoto T., Kugiyama K., Ogawa H., Yasue H., 1999. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. Journal of the American College of Cardiology.1;34(1), 146-54.
76. Prockop D.J., Kivirikko K.I., 1995. Collagens: molecular biology, diseases, and potentials for therapy. Annual Review of Biochemistry. 64(1), 403-34.
77. Peterkofsky B., 1991. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. The American Journal of Clinical Nutrition.1;54(6), 1135S-40S.
78. Nusgens B.V., Colige A.C., Lambert C.A., Lapière C.M., Humbert P., Rougier A., Haftek M., Richard A., Creidi P., 2001, Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. Journal of Investigative Dermatology.1;116(6), 853-9.
79. Taylor A., 1992. Role of nutrients in delaying cataracts. Annals of the New York Academy of Sciences. 30; 669:111.
80. Bjelakovic G., Nikolova D., Gluud L.L., Simonetti R.G., Gluud C., 2012, Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews. (3), 1-8.
81. Møller P., Vogel U., Pedersen A., Dragsted L.O., Sandström B., Loft S., 2003. No effect of 600 grams fruit and vegetables per day on oxidative DNA damage and repair in healthy nonsmokers. Cancer Epidemiology and Prevention Biomarkers. 1;12(10), 1016-22.
82. Naili M., Errayes A., Alghazeer R., Mohammed W. A., Darwish M., 2020. Evaluation of Antimicrobial and Antioxidant Activities of Psidium guajava L growing in Libya. International Journal of Advanced Biological and Biomedical Research. 8(4), 419-428.
83. Salganik R.I., 2001, The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. Journal of the American College of Nutrition.1;20(sup5), 464S-72S.
84. Mahdieh G., Fazilati M., Izadi M., Pilehvarian A., Nazem H., 2020, Investigation of ACE Inhibitory Effect and Antioxidant Activity of Peptide Extracted from Spirulina Platensis, Chemical Methodologies. 4(2), 172-180.
85. Ataei Moghadam S., Rostami Charati F., Akbari R., Gholamalipour Alamdari E., Behmanesh B., 2020, Consideration antimicrobial and antioxidant properties of anbarnesa smoke ointment. Journal of Medicinal and Chemical Sciences. 3(3), 245-253.
86. Yousefi S., Nemati Karimooy F., Miyanbandi T., Esmaeilpour F., 2020, Dietary Supplementing with Resveratrol Improves Antioxidant Status in Hypercholestrolemic Rats. GMJ Medicine. 1(2), 72-78.
87. Gupta M., Panizai M., Tareen M., Ortega-Martinez S., Doreulee N., 2020. An Overview on Novel Antioxidant and Anti-Cancer Properties of Lycopene: A Comprehensive Revie'. GMJ Medicine. 1(2), 43-48.
88. Shahamatpour M., Tabatabaee Ghomsheh S.M., Maghsoudi S., Azizi S., 2021, Fenton Processes, Adsorption and Nano Filtration in Industrial Wastewater Treatment, Progress in Chemical and Biochemical Research. 4(1), 31-43.
89. El-Shahaby O., El-Zayat M., Rabei R., Aldesuquy H.S., 2019, Phytochemical constituents, antioxidant activity and antimicrobial potential of Pulicaria incisa (lam.) DC as a folk medicinal plant. Progress in Chemical and Biochemical Research. 2(4), 222-227.
90. El-Shahaby O.A., El-Zayat M., Abd El-Fattah, G., El-Hefny M.M., 2019. Evaluation of the biological activity of Capparis spinosa var. aegyptiaca essential oils and fatty constituents as Anticipated Antioxidant and Antimicrobial Agents. Progress in Chemical and Biochemical Research. 2(4), 211-221.
91. Hagr T., Adam I., 2020, Phytochemical Analysis, Antibacterial and antioxidant Activities of Essential Oil from Hibiscus sabdariffa (L.) Seeds, (Sudanese Karkadi). Progress in Chemical and Biochemical Research. 3(3), 194-201.
92. Thacker H., Ram V., Dave P.N., 2019. Plant mediated synthesis of Iron nanoparticles and their Applications: A Review. Progress in Chemical and Biochemical Research. 2(3), 84-91.
93. Fazeli-Nasab B., Khajeh H., Rahmani A.F., 2021. Effects of culture medium and plant hormones in organogenesis in olive (CV. Kroneiki). J Plant Bioinform Biotech. 1(1), 1-13.
94. Mursu J., Robien K., Harnack L.J., Park K., Jacobs D.R., 2011, Dietary supplements and mortality rate in older women: the Iowa Women's Health Study. Archives of Internal Medicine. 10;171(18), 1625-33.
95. MacLennan R., Macrae F., Bain C., Battistutta D., Chapuis P., Gratten H., Lambert J., Newland R.C., Ngu M., Russell A., Ward M., 1995. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. JNCI Journal of the National Cancer Institute. 6;87(23), 1760-6.
96. Terwanger Philip T., Asemave K., Obochi G.O., 2021. Comparative Assessment of Phytochemicals in Four (4) Varieties of Ananas Comosus (L.) Merr Peels. Progress in Chemical and Biochemical Research. 4(1), 1-10.
97. Asemave K., Anure T., 2019. The bioactivities of the neem (seeds and leaves) against Callosobruchus maculatus on a Vigna Subterranean L. Progress in Chemical and Biochemical Research. 2(3), 92-98.