<p>Sir,</p> <p>Oxidative stress is referred to imbalance between the reactive oxygen species and antioxidants system to detoxify the reactive intermediates or to repair the resulting damage. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>Although oxidation reactions are crucial for life, they can also be damaging. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup>Insufficient levels of antioxidants or inhibition of the antioxidant enzymes, cause oxidative stress which may damage all components of the cell, including proteins, lipids and deoxyribonucleic acid. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>The oxidative stress is thought to be involved in the development of atherosclerosis, heart failure, myocardial infarction, cancer, Parkinson′s disease, Alzheimer′s disease, sickle cell disease, lichen planus, vitiligo, autism, chronic fatigue syndrome and renal failure. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref10">10</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref11">11</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref12">12</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>Antioxidants are reducing agents such as thiols, ascorbic acid, or polyphenols molecules that inhibit the oxidation of other molecules by being oxidized themselves. Plants and animals maintain complex systems of multiple types of antioxidants such as glutathione, vitamin C, vitamin A and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>Antioxidants are widely used in dietary supplements and have been investigated for the prevention of diseases such as cancer, coronary heart disease and even altitude sickness. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials with a limited number of antioxidants detected no benefit and even suggested that excess supplementation with certain putative antioxidants may be harmful. <sup> <xref ref-type="bibr" rid="ref11">11</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>From the literature review we may conclude that the diets high in antioxidants (fruits and vegetables) are nearly almost beneficial, but this is not the case for diet supplementations. The possible explanation is that, in the diet, there is a mix of antioxidants and it is well recognized that they work as a continuous chain, while supplementation is usually given using one or two substances. Therefore, the antioxidant chain is not completely available. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>In this regard, it is well-known that after scavenging free radicals, if an antioxidant is not restored by the following antioxidant in the chain, it begins to be a pro-oxidant. In this situation, the final effect of such supplementations would be no effect or a damaging effect. <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref15">15</xref> </sup>Therefore, in antioxidant therapy complimentary antioxidants cannot always substitute the fruits and vegetables high in antioxidants.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Halliwell</surname> <given-names>B</given-names> </name> </person-group> <article-title>Free radicals and antioxidants: Updating a personal view</article-title> <source>Nutr Rev</source> <year>2012</year> <volume>70</volume> <fpage>257</fpage> <lpage>65</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>2</surname> <given-names></given-names> </name> </person-group> <article-title>Rafieian-Kopaei M, Baradaran A, Rafieian M.Plants antioxidants: From laboratory to clinic</article-title> <source>J Nephropathology</source> <year>2013</year> <volume>2</volume> <fpage>152</fpage> <lpage>3</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>3</surname> <given-names></given-names> </name> </person-group> <article-title>Minaiyan M, Ghannadi AR, Mahzouni P, Abed AR.Preventive effect of Cichorium Intybus L</article-title> <source>Two extracts on cerulein-induced acute pancreatitis in mice</source> <year></year> <volume></volume> <fpage></fpage> <comment>Minaiyan M, Ghannadi AR, Mahzouni P, Abed AR Preventive effect of Cichorium Intybus L Two extracts on cerulein-induced acute pancreatitis in mice Int J Prev Med 2012;3:351-7</comment> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>4</surname> <given-names></given-names> </name> </person-group> <article-title>Tabesh M, Hariri M, Askari G, Ghiasvand R, Tabesh M, Heydari A, et al.The relationship between vegetables and fruits intake and glycosylated hemoglobin values, lipids profiles and nitrogen status in type II inactive diabetic patients</article-title> <source>Int J Prev Med</source> <year>2013</year> <volume>4 (Suppl 1)</volume> <fpage>S63</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>5</surname> <given-names></given-names> </name> </person-group> <article-title>Sahni N, Gupta KL.Dietary antioxidants and oxidative stress in predialysis chronic kidney disease patients</article-title> <source>J Nephropatholology</source> <year>2012</year> <volume>1</volume> <fpage>134</fpage> <lpage>42</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>6</surname> <given-names></given-names> </name> </person-group> <article-title>Vafa MR, Haghighatjoo E, Shidfar F, Afshari S, Gohari MR, Ziaee A.Effects of apple consumption on lipid profile of hyperlipidemic and overweight men</article-title> <source>Int J Prev Med</source> <year>2011</year> <volume>2</volume> <fpage>94</fpage> <lpage>100</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>7</surname> <given-names></given-names> </name> </person-group> <article-title>Tavafi M.Diabetic nephropathy and antioxidants</article-title> <source>J Nephropatholology</source> <year>2013</year> <volume>2</volume> <fpage>20</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref8"> <label>8</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>8</surname> <given-names></given-names> </name> </person-group> <article-title>Nasri H, Nematbakhsh M, Ghobadi S, Ansari R, Shahinfard N, Rafieian-Kopaei M.Preventive and curative effects of ginger extract against histopathologic changes of gentamicin-induced tubular toxicity in rats</article-title> <source>Int J Prev Med</source> <year>2013</year> <volume>4</volume> <fpage>316</fpage> <lpage>21</lpage> </nlm-citation> </ref> <ref id="ref9"> <label>9</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>9</surname> <given-names></given-names> </name> </person-group> <article-title>Solati M, Mahboobi HR.Paraoxonase enzyme activity and dyslipidemia in chronic kidney disease patients</article-title> <source>J Nephropatholology</source> <year>2012</year> <volume>1</volume> <fpage>123</fpage> <lpage>5</lpage> </nlm-citation> </ref> <ref id="ref10"> <label>10</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>10</surname> <given-names></given-names> </name> </person-group> <article-title>Rafieian-Kopaei M, Nasri H, Nematbakhsh M, Baradaran A, Gheissari A, RouhiH, et al.Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study</article-title> <source>J Nephropatholology</source> <year>2012</year> <volume>1</volume> <fpage>109</fpage> <lpage>16</lpage> </nlm-citation> </ref> <ref id="ref11"> <label>11</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>11</surname> <given-names></given-names> </name> </person-group> <article-title>Baillie JK, Thompson AA, Irving JB, Bates MG, Sutherland AI, Macnee W, et al.Oral antioxidant supplementation does not prevent acute mountain sickness: Double blind, randomized placebo-controlled trial</article-title> <source>QJM</source> <year>2009</year> <volume>102</volume> 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JRMS

J Res Med Sci

Journal of Research in Medical Sciences

1735-1995 1735-7136

Medknow Publications Pvt Ltd

India

JRMS-18-629

24516501

Letter To Editor

Oxidative stress and the paradoxical effects of antioxidants

Rafieian-Kopaei

Mahmoud

Baradaran

Azar

Rafieian

Morteza

Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

Address for correspondence:Mahmoud Rafieian-Kopaei, Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran rafieian@yahoo.com

July 2013

18 7 629 629

2013

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

<p>Sir,</p> <p>Oxidative stress is referred to imbalance between the reactive oxygen species and antioxidants system to detoxify the reactive intermediates or to repair the resulting damage. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>Although oxidation reactions are crucial for life, they can also be damaging. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup>Insufficient levels of antioxidants or inhibition of the antioxidant enzymes, cause oxidative stress which may damage all components of the cell, including proteins, lipids and deoxyribonucleic acid. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>The oxidative stress is thought to be involved in the development of atherosclerosis, heart failure, myocardial infarction, cancer, Parkinson′s disease, Alzheimer′s disease, sickle cell disease, lichen planus, vitiligo, autism, chronic fatigue syndrome and renal failure. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref10">10</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref11">11</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref12">12</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>Antioxidants are reducing agents such as thiols, ascorbic acid, or polyphenols molecules that inhibit the oxidation of other molecules by being oxidized themselves. Plants and animals maintain complex systems of multiple types of antioxidants such as glutathione, vitamin C, vitamin A and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>Antioxidants are widely used in dietary supplements and have been investigated for the prevention of diseases such as cancer, coronary heart disease and even altitude sickness. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials with a limited number of antioxidants detected no benefit and even suggested that excess supplementation with certain putative antioxidants may be harmful. <sup> <xref ref-type="bibr" rid="ref11">11</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>From the literature review we may conclude that the diets high in antioxidants (fruits and vegetables) are nearly almost beneficial, but this is not the case for diet supplementations. The possible explanation is that, in the diet, there is a mix of antioxidants and it is well recognized that they work as a continuous chain, while supplementation is usually given using one or two substances. Therefore, the antioxidant chain is not completely available. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>In this regard, it is well-known that after scavenging free radicals, if an antioxidant is not restored by the following antioxidant in the chain, it begins to be a pro-oxidant. In this situation, the final effect of such supplementations would be no effect or a damaging effect. <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref15">15</xref> </sup>Therefore, in antioxidant therapy complimentary antioxidants cannot always substitute the fruits and vegetables high in antioxidants.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Halliwell</surname> <given-names>B</given-names> </name> </person-group> <article-title>Free radicals and antioxidants: Updating a personal view</article-title> <source>Nutr Rev</source> <year>2012</year> <volume>70</volume> <fpage>257</fpage> <lpage>65</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>2</surname> <given-names></given-names> </name> </person-group> <article-title>Rafieian-Kopaei M, Baradaran A, Rafieian M.Plants antioxidants: From laboratory to clinic</article-title> <source>J Nephropathology</source> <year>2013</year> <volume>2</volume> <fpage>152</fpage> <lpage>3</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>3</surname> <given-names></given-names> </name> </person-group> <article-title>Minaiyan M, Ghannadi AR, Mahzouni P, Abed AR.Preventive effect of Cichorium Intybus L</article-title> <source>Two extracts on cerulein-induced acute pancreatitis in mice</source> <year></year> <volume></volume> <fpage></fpage> <comment>Minaiyan M, Ghannadi AR, Mahzouni P, Abed AR Preventive effect of Cichorium Intybus L Two extracts on cerulein-induced acute pancreatitis in mice Int J Prev Med 2012;3:351-7</comment> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>4</surname> <given-names></given-names> </name> </person-group> <article-title>Tabesh M, Hariri M, Askari G, Ghiasvand R, Tabesh M, Heydari A, et al.The relationship between vegetables and fruits intake and glycosylated hemoglobin values, lipids profiles and nitrogen status in type II inactive diabetic patients</article-title> <source>Int J Prev Med</source> <year>2013</year> <volume>4 (Suppl 1)</volume> <fpage>S63</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>5</surname> <given-names></given-names> </name> </person-group> <article-title>Sahni N, Gupta KL.Dietary antioxidants and oxidative stress in predialysis chronic kidney disease patients</article-title> <source>J Nephropatholology</source> <year>2012</year> <volume>1</volume> <fpage>134</fpage> <lpage>42</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>6</surname> <given-names></given-names> </name> </person-group> <article-title>Vafa MR, Haghighatjoo E, Shidfar F, Afshari S, Gohari MR, Ziaee A.Effects of apple consumption on lipid profile of hyperlipidemic and overweight men</article-title> <source>Int J Prev Med</source> <year>2011</year> <volume>2</volume> <fpage>94</fpage> <lpage>100</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>7</surname> <given-names></given-names> </name> </person-group> <article-title>Tavafi M.Diabetic nephropathy and antioxidants</article-title> <source>J Nephropatholology</source> <year>2013</year> <volume>2</volume> <fpage>20</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref8"> <label>8</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>8</surname> <given-names></given-names> </name> </person-group> <article-title>Nasri H, Nematbakhsh M, Ghobadi S, Ansari R, Shahinfard N, Rafieian-Kopaei M.Preventive and curative effects of ginger extract against histopathologic changes of gentamicin-induced tubular toxicity in rats</article-title> <source>Int J Prev Med</source> <year>2013</year> <volume>4</volume> <fpage>316</fpage> <lpage>21</lpage> </nlm-citation> </ref> <ref id="ref9"> <label>9</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>9</surname> <given-names></given-names> </name> </person-group> <article-title>Solati M, Mahboobi HR.Paraoxonase enzyme activity and dyslipidemia in chronic kidney disease patients</article-title> <source>J Nephropatholology</source> <year>2012</year> <volume>1</volume> <fpage>123</fpage> <lpage>5</lpage> </nlm-citation> </ref> <ref id="ref10"> <label>10</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>10</surname> <given-names></given-names> </name> </person-group> <article-title>Rafieian-Kopaei M, Nasri H, Nematbakhsh M, Baradaran A, Gheissari A, RouhiH, et al.Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study</article-title> <source>J Nephropatholology</source> <year>2012</year> <volume>1</volume> <fpage>109</fpage> <lpage>16</lpage> </nlm-citation> </ref> <ref id="ref11"> <label>11</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>11</surname> <given-names></given-names> </name> </person-group> <article-title>Baillie JK, Thompson AA, Irving JB, Bates MG, Sutherland AI, Macnee W, et al.Oral antioxidant supplementation does not prevent acute mountain sickness: Double blind, randomized placebo-controlled trial</article-title> <source>QJM</source> <year>2009</year> <volume>102</volume> 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