<p>Sir,</p> <p>We read with great interest the article by Hemati and colleagues, entitled "The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity (CIN) in cancer patients treated with cisplatin (CP)-based chemotherapy: A randomized, placebo-controlled study," published recently in your esteemed journal. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>They studied 22 patients, who received 400 IU vitamin E and 200 μg selenium daily and 24 patients received placebo. They found significant differences in glomerular filtration rate between the two groups after the third cycle and 1 month after the end of chemotherapy. They concluded that vitamin E and selenium can be used to reduce CIN. We congratulate the authors for their findings and their effort to find a way to reduce CIN. However, we would like to clarify a few points about CIN. In a preclinical study to find the protective role of endogenous nitric oxide donor (L-arginine) in CIN, we studied 33 Wistar rats and we found, L-arginine had protective effects against CIN in males, however, it promotes the induced damage in females. We concluded a gender related difference in rat model of CIN. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Likewise, to the study of Hemati et al., ameliorative effects of viamin E was also found in our another study on 32 Wistar rats. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>We also showed the renoprotective effects of Losartan as an angiotensin II receptor 1 (AT1) blockade in CIN in rats. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>Surprisingly, we also found a low dose of magnesium (Mg) supplementation intensifies kidney toxicity and renal dysfunction in CIN in the rat model. We concluded that, the protective role of Mg with moderate and high doses is not certain. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>We also observed that co-administration of vitamin C and losartan was not more effective than the administration of vitamin C or Losartan alone. <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>While, the role of gender in CIN is not well known, we conducted a study on rat model of CP nephrotoxicity and observed, losartan may prevent CIN in males, but it promotes the CP-induced damage in females, which may be related to the renin-angiotensin system receptors in the kidneys. <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>Additionally, we recently reported that, vitamin E, vitamin C, or losartan is not nephroprotectant against CIN in presence of estrogen in ovariectomized rat model, <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>which is in agreement with our previous findings. More recently we observed that estrogen abolished protective effect of erythropoietin against CIN in ovariectomized rats, <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup>while renoprotective effects of erythropoietin was also shown in our previous study. <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>Hence, it is well documented that there is a gender difference in the CIN in the rat model. It is documented that some cases of chronic renal diseases are gender related too. <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref15">15</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref16">16</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref17">17</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref18">18</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref19">19</xref> </sup>Few studies published regarding the sex difference in CIN. <sup> <xref ref-type="bibr" rid="ref19">19</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref20">20</xref> </sup>Hence, there still remains a number of big questions to further explore mechanisms interact in CIN. We propose to conduct clinical studies to understand the factor of gender difference in CIN.</p> <p>Accordingly, in Hemati et al., study the distribution of gender was not specified. In our recent study (not publish data) the effect of vitamin E on CIN also was gender depended.</p> <p>It is our pleasure to recommend some suggestions for further studies in this area;</p> <p> <list list-type="bullet"> <list-item> <p>Selenium is a component of the antioxidant enzymes glutathione peroxidase and thioredoxin reductase. Vitamin E also is an antioxidant. In this study, both of this antioxidant were supplemented. Therefore, the positive reported results may obtain by one of each or both. On the other hand, antioxidants may have interaction too. So, we suggest single supplementation for such similar study</p> </list-item> <list-item> <p>As mentioned before, sex-based difference in CIN should be considered in similar studies. Sex hormone; estrogen may abolish the effect of antioxidant supplementation <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup></p> </list-item> <list-item> <p>Given more data for kidney functions such as blood urea nitrogen and creatinine, and also more data such as Malondialdehyde, superoxidase dismutase or glutathione to evaluate the oxidative stress is extremely important. Comparison these data before and after CP therapy will provide a better conclusion</p> </list-item> <list-item> <p>Using advance statistical analysis may provide more scientific conclusions about the effect of supplementation, and finally</p> </list-item> <list-item> <p>We have to be sure that antioxidant supplementation should not reduce the effect of CP on the tumor target. So special attention is needed for antioxidant selection, especially in clinical trials.</p> </list-item> </list> </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>Hemati</surname> <given-names>S</given-names> </name> <name> <surname>Arbab Jolfaie</surname> <given-names>N</given-names> </name> <name> <surname>Rafienia</surname> <given-names>M</given-names> </name> <name> <surname>Ghavamnasiri</surname> <given-names>M</given-names> </name> </person-group> <article-title>The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity in cancer patients treated with cisplatin-based chemotherapy: A randomized, placebo-controlled study</article-title> <source>J Res Med Sci</source> <year>2012</year> <volume>17</volume> <fpage>S49</fpage> <lpage>58</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Haghighi</surname> <given-names>M</given-names> </name> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <etal /> </person-group> <article-title>The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model</article-title> <source>J Res Med Sci</source> <year>2011</year> <volume>16</volume> <fpage>1389</fpage> <lpage>96</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Safari</surname> <given-names>T</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Mortazavi</surname> <given-names>M</given-names> </name> <etal /> </person-group> <article-title>Administration of vitamin E and losartan as prophylaxes in cisplatin-induced nephrotoxicity model in rats</article-title> <source>J Nephrol</source> <year>2012</year> <volume>25</volume> <fpage>410</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Haghshenas</surname> <given-names>S</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <etal /> </person-group> <article-title>The role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: No nephroprotectant effect</article-title> <source>Int J Prev Med</source> <year>2012</year> <volume>3</volume> <fpage>637</fpage> <lpage>43</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Safari</surname> <given-names>T</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Khazaei</surname> <given-names>M</given-names> </name> <etal /> </person-group> <article-title>A combination of vitamin C and losartan for cisplatin-induced nephrotoxicity in rats</article-title> <source>Iran J Kidney Dis</source> <year>2012</year> <volume>6</volume> <fpage>361</fpage> <lpage>5</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <name> <surname>Fatahi</surname> <given-names>Z</given-names> </name> <name> <surname>Kianpoor</surname> <given-names>F</given-names> </name> <name> <surname>Sanei</surname> <given-names>MH</given-names> </name> <etal /> </person-group> <article-title>A histopathological study of nephrotoxicity, hepatoxicity or testicular toxicity: Which one is the first observation as side effect of cisplatin-induced toxicity in animal model.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>190</fpage> <lpage>3</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Haghighi</surname> <given-names>M</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Roshanaei</surname> <given-names>K</given-names> </name> <etal /> </person-group> <article-title>The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: Gender-related differences</article-title> <source>Ren Fail</source> <year>2012</year> <volume>34</volume> <fpage>1046</fpage> <lpage>51</lpage> </nlm-citation> </ref> <ref id="ref8"> <label>8</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <etal /> </person-group> <article-title>Vitamin E, Vitamin C, or Losartan Is Not Nephroprotectant against Cisplatin-Induced Nephrotoxicity in Presence of Estrogen in Ovariectomized Rat Model</article-title> <source>Int J Nephrol</source> <year>2012</year> <volume>2012</volume> <fpage>284896</fpage> </nlm-citation> </ref> <ref id="ref9"> <label>9</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Mazaheri</surname> <given-names>S</given-names> </name> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <etal /> </person-group> <article-title>Estrogen abolishes protective effect of erythropoietin against cisplatin-induced nephrotoxicity in ovariectomized rats.ISRN Oncol</article-title> <source></source> <year>2012</year> <volume>2012</volume> <fpage>890310</fpage> <comment>doi: 10.5402/2012/</comment> </nlm-citation> </ref> <ref id="ref10"> <label>10</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Rafieian-Kopaei</surname> <given-names>M</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Baradaran</surname> <given-names>A</given-names> </name> <name> <surname>Gheissari</surname> <given-names>A</given-names> </name> <name> <surname>Rouhi</surname> <given-names>H</given-names> </name> <etal /> </person-group> <article-title>Erythropoietin ameliorates gentamycin-induced renal toxicity: A biochemical and histopathological study.J Nephropathology</article-title> <source></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="book"> <person-group person-group-type="author"> <name> <surname>Kadkhodaee</surname> <given-names>M</given-names> </name> </person-group> <article-title>2012;1:81-2</article-title> <source></source> <publisher-loc></publisher-loc> <publisher-name></publisher-name> <year>2012</year> <volume></volume> <fpage>1</fpage> <lpage>2</lpage> </nlm-citation> </ref> <ref id="ref12"> <label>12</label> <nlm-citation citation-type="book"> <person-group person-group-type="author"> <name> <surname>Tavafi</surname> <given-names>M</given-names> </name> </person-group> <article-title>2012;1:83-6</article-title> <source></source> <publisher-loc></publisher-loc> <publisher-name></publisher-name> <year>2012</year> <volume></volume> <fpage>3</fpage> <lpage>6</lpage> </nlm-citation> </ref> <ref id="ref13"> <label>13</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Solati</surname> <given-names>M</given-names> </name> <name> <surname>Mahboobi</surname> <given-names>HR</given-names> </name> </person-group> <article-title>Paraoxonase enzyme activity and dyslipidemia in chronic kidney disease patients.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>123</fpage> <lpage>5</lpage> </nlm-citation> </ref> <ref id="ref14"> <label>14</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Sahni</surname> <given-names>N</given-names> </name> <name> <surname>Gupta</surname> <given-names>KL</given-names> </name> </person-group> <article-title>Dietary antioxidents and oxidative stress in predialysis chronic kidney disease patients.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>134</fpage> <lpage>42</lpage> </nlm-citation> </ref> <ref id="ref15"> <label>15</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Rahimi</surname> <given-names>Z</given-names> </name> </person-group> <article-title>ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>143</fpage> <lpage>51</lpage> </nlm-citation> </ref> <ref id="ref16"> <label>16</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Kari</surname> <given-names>J</given-names> </name> </person-group> <article-title>Epidemiology of chronic kidney disease in children.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>162</fpage> <lpage>3</lpage> </nlm-citation> </ref> <ref id="ref17"> <label>17</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Assadi</surname> <given-names>F</given-names> </name> </person-group> <article-title>The epidemic of pediatric chronic kidney disease: The danger of skepticism.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>61</fpage> <lpage>4</lpage> </nlm-citation> </ref> <ref id="ref18"> <label>18</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Khajehdehi</surname> <given-names>P</given-names> </name> </person-group> <article-title>Turmeric: Reemerging of a neglected Asian traditional remedy.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>17</fpage> <lpage>22</lpage> </nlm-citation> </ref> <ref id="ref19"> <label>19</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Kang</surname> <given-names>DH</given-names> </name> <name> <surname>Yu</surname> <given-names>ES</given-names> </name> <name> <surname>Yoon</surname> <given-names>KI</given-names> </name> <name> <surname>Johnson</surname> <given-names>R</given-names> </name> </person-group> <article-title>The impact of gender on progression of renal disease: Potential role of estrogen-mediated vascular endothelial growth factor regulation and vascular protection</article-title> <source>Am J Pathol</source> <year>2004</year> <volume>164</volume> <fpage>679</fpage> <lpage>88</lpage> </nlm-citation> </ref> <ref id="ref20"> <label>20</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ghorbani</surname> <given-names>A</given-names> </name> </person-group> <article-title>Renal protective effect of selenium on cisplatin-induced nephrotoxicity</article-title> <source>J Ren Inj Prev</source> <year>2012</year> <volume>1</volume> <fpage>31</fpage> <lpage>2</lpage> </nlm-citation> </ref> <ref id="ref21"> <label>21</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"></person-group> <article-title></article-title> <source></source> <year></year> <volume></volume> <fpage></fpage> </nlm-citation> </ref> </ref-list> </back> </article>

JRMS

J Res Med Sci

Journal of Research in Medical Sciences

1735-1995 1735-7136

Medknow Publications Pvt Ltd

India

JRMS-18-626

24516499

Letter To Editor

The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity in cancer patients treated with cisplatin-based chemotherapy: A randomized, placebo-controlled study

Nematbakhsh

Mehdi

Nasri

Hamid

Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran

Address for correspondence:Hamid Nasri, Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran hamidnasri@med.mui.ac.ir

July 2013

18 7 626 627

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>We read with great interest the article by Hemati and colleagues, entitled "The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity (CIN) in cancer patients treated with cisplatin (CP)-based chemotherapy: A randomized, placebo-controlled study," published recently in your esteemed journal. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>They studied 22 patients, who received 400 IU vitamin E and 200 μg selenium daily and 24 patients received placebo. They found significant differences in glomerular filtration rate between the two groups after the third cycle and 1 month after the end of chemotherapy. They concluded that vitamin E and selenium can be used to reduce CIN. We congratulate the authors for their findings and their effort to find a way to reduce CIN. However, we would like to clarify a few points about CIN. In a preclinical study to find the protective role of endogenous nitric oxide donor (L-arginine) in CIN, we studied 33 Wistar rats and we found, L-arginine had protective effects against CIN in males, however, it promotes the induced damage in females. We concluded a gender related difference in rat model of CIN. <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Likewise, to the study of Hemati et al., ameliorative effects of viamin E was also found in our another study on 32 Wistar rats. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>We also showed the renoprotective effects of Losartan as an angiotensin II receptor 1 (AT1) blockade in CIN in rats. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>Surprisingly, we also found a low dose of magnesium (Mg) supplementation intensifies kidney toxicity and renal dysfunction in CIN in the rat model. We concluded that, the protective role of Mg with moderate and high doses is not certain. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>We also observed that co-administration of vitamin C and losartan was not more effective than the administration of vitamin C or Losartan alone. <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>While, the role of gender in CIN is not well known, we conducted a study on rat model of CP nephrotoxicity and observed, losartan may prevent CIN in males, but it promotes the CP-induced damage in females, which may be related to the renin-angiotensin system receptors in the kidneys. <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>Additionally, we recently reported that, vitamin E, vitamin C, or losartan is not nephroprotectant against CIN in presence of estrogen in ovariectomized rat model, <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>which is in agreement with our previous findings. More recently we observed that estrogen abolished protective effect of erythropoietin against CIN in ovariectomized rats, <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup>while renoprotective effects of erythropoietin was also shown in our previous study. <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>Hence, it is well documented that there is a gender difference in the CIN in the rat model. It is documented that some cases of chronic renal diseases are gender related too. <sup> <xref ref-type="bibr" rid="ref13">13</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref14">14</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref15">15</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref16">16</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref17">17</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref18">18</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref19">19</xref> </sup>Few studies published regarding the sex difference in CIN. <sup> <xref ref-type="bibr" rid="ref19">19</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref20">20</xref> </sup>Hence, there still remains a number of big questions to further explore mechanisms interact in CIN. We propose to conduct clinical studies to understand the factor of gender difference in CIN.</p> <p>Accordingly, in Hemati et al., study the distribution of gender was not specified. In our recent study (not publish data) the effect of vitamin E on CIN also was gender depended.</p> <p>It is our pleasure to recommend some suggestions for further studies in this area;</p> <p> <list list-type="bullet"> <list-item> <p>Selenium is a component of the antioxidant enzymes glutathione peroxidase and thioredoxin reductase. Vitamin E also is an antioxidant. In this study, both of this antioxidant were supplemented. Therefore, the positive reported results may obtain by one of each or both. On the other hand, antioxidants may have interaction too. So, we suggest single supplementation for such similar study</p> </list-item> <list-item> <p>As mentioned before, sex-based difference in CIN should be considered in similar studies. Sex hormone; estrogen may abolish the effect of antioxidant supplementation <sup> <xref ref-type="bibr" rid="ref8">8</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref9">9</xref> </sup></p> </list-item> <list-item> <p>Given more data for kidney functions such as blood urea nitrogen and creatinine, and also more data such as Malondialdehyde, superoxidase dismutase or glutathione to evaluate the oxidative stress is extremely important. Comparison these data before and after CP therapy will provide a better conclusion</p> </list-item> <list-item> <p>Using advance statistical analysis may provide more scientific conclusions about the effect of supplementation, and finally</p> </list-item> <list-item> <p>We have to be sure that antioxidant supplementation should not reduce the effect of CP on the tumor target. So special attention is needed for antioxidant selection, especially in clinical trials.</p> </list-item> </list> </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>Hemati</surname> <given-names>S</given-names> </name> <name> <surname>Arbab Jolfaie</surname> <given-names>N</given-names> </name> <name> <surname>Rafienia</surname> <given-names>M</given-names> </name> <name> <surname>Ghavamnasiri</surname> <given-names>M</given-names> </name> </person-group> <article-title>The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity in cancer patients treated with cisplatin-based chemotherapy: A randomized, placebo-controlled study</article-title> <source>J Res Med Sci</source> <year>2012</year> <volume>17</volume> <fpage>S49</fpage> <lpage>58</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Haghighi</surname> <given-names>M</given-names> </name> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <etal /> </person-group> <article-title>The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model</article-title> <source>J Res Med Sci</source> <year>2011</year> <volume>16</volume> <fpage>1389</fpage> <lpage>96</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Safari</surname> <given-names>T</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Mortazavi</surname> <given-names>M</given-names> </name> <etal /> </person-group> <article-title>Administration of vitamin E and losartan as prophylaxes in cisplatin-induced nephrotoxicity model in rats</article-title> <source>J Nephrol</source> <year>2012</year> <volume>25</volume> <fpage>410</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Haghshenas</surname> <given-names>S</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <etal /> </person-group> <article-title>The role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: No nephroprotectant effect</article-title> <source>Int J Prev Med</source> <year>2012</year> <volume>3</volume> <fpage>637</fpage> <lpage>43</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Safari</surname> <given-names>T</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Khazaei</surname> <given-names>M</given-names> </name> <etal /> </person-group> <article-title>A combination of vitamin C and losartan for cisplatin-induced nephrotoxicity in rats</article-title> <source>Iran J Kidney Dis</source> <year>2012</year> <volume>6</volume> <fpage>361</fpage> <lpage>5</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <name> <surname>Fatahi</surname> <given-names>Z</given-names> </name> <name> <surname>Kianpoor</surname> <given-names>F</given-names> </name> <name> <surname>Sanei</surname> <given-names>MH</given-names> </name> <etal /> </person-group> <article-title>A histopathological study of nephrotoxicity, hepatoxicity or testicular toxicity: Which one is the first observation as side effect of cisplatin-induced toxicity in animal model.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>190</fpage> <lpage>3</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Haghighi</surname> <given-names>M</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Roshanaei</surname> <given-names>K</given-names> </name> <etal /> </person-group> <article-title>The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: Gender-related differences</article-title> <source>Ren Fail</source> <year>2012</year> <volume>34</volume> <fpage>1046</fpage> <lpage>51</lpage> </nlm-citation> </ref> <ref id="ref8"> <label>8</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <name> <surname>Ashrafi</surname> <given-names>F</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <etal /> </person-group> <article-title>Vitamin E, Vitamin C, or Losartan Is Not Nephroprotectant against Cisplatin-Induced Nephrotoxicity in Presence of Estrogen in Ovariectomized Rat Model</article-title> <source>Int J Nephrol</source> <year>2012</year> <volume>2012</volume> <fpage>284896</fpage> </nlm-citation> </ref> <ref id="ref9"> <label>9</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Pezeshki</surname> <given-names>Z</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Mazaheri</surname> <given-names>S</given-names> </name> <name> <surname>Eshraghi-Jazi</surname> <given-names>F</given-names> </name> <name> <surname>Talebi</surname> <given-names>A</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <etal /> </person-group> <article-title>Estrogen abolishes protective effect of erythropoietin against cisplatin-induced nephrotoxicity in ovariectomized rats.ISRN Oncol</article-title> <source></source> <year>2012</year> <volume>2012</volume> <fpage>890310</fpage> <comment>doi: 10.5402/2012/</comment> </nlm-citation> </ref> <ref id="ref10"> <label>10</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Rafieian-Kopaei</surname> <given-names>M</given-names> </name> <name> <surname>Nasri</surname> <given-names>H</given-names> </name> <name> <surname>Nematbakhsh</surname> <given-names>M</given-names> </name> <name> <surname>Baradaran</surname> <given-names>A</given-names> </name> <name> <surname>Gheissari</surname> <given-names>A</given-names> </name> <name> <surname>Rouhi</surname> <given-names>H</given-names> </name> <etal /> </person-group> <article-title>Erythropoietin ameliorates gentamycin-induced renal toxicity: A biochemical and histopathological study.J Nephropathology</article-title> <source></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="book"> <person-group person-group-type="author"> <name> <surname>Kadkhodaee</surname> <given-names>M</given-names> </name> </person-group> <article-title>2012;1:81-2</article-title> <source></source> <publisher-loc></publisher-loc> <publisher-name></publisher-name> <year>2012</year> <volume></volume> <fpage>1</fpage> <lpage>2</lpage> </nlm-citation> </ref> <ref id="ref12"> <label>12</label> <nlm-citation citation-type="book"> <person-group person-group-type="author"> <name> <surname>Tavafi</surname> <given-names>M</given-names> </name> </person-group> <article-title>2012;1:83-6</article-title> <source></source> <publisher-loc></publisher-loc> <publisher-name></publisher-name> <year>2012</year> <volume></volume> <fpage>3</fpage> <lpage>6</lpage> </nlm-citation> </ref> <ref id="ref13"> <label>13</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Solati</surname> <given-names>M</given-names> </name> <name> <surname>Mahboobi</surname> <given-names>HR</given-names> </name> </person-group> <article-title>Paraoxonase enzyme activity and dyslipidemia in chronic kidney disease patients.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>123</fpage> <lpage>5</lpage> </nlm-citation> </ref> <ref id="ref14"> <label>14</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Sahni</surname> <given-names>N</given-names> </name> <name> <surname>Gupta</surname> <given-names>KL</given-names> </name> </person-group> <article-title>Dietary antioxidents and oxidative stress in predialysis chronic kidney disease patients.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>134</fpage> <lpage>42</lpage> </nlm-citation> </ref> <ref id="ref15"> <label>15</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Rahimi</surname> <given-names>Z</given-names> </name> </person-group> <article-title>ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>143</fpage> <lpage>51</lpage> </nlm-citation> </ref> <ref id="ref16"> <label>16</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Kari</surname> <given-names>J</given-names> </name> </person-group> <article-title>Epidemiology of chronic kidney disease in children.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>162</fpage> <lpage>3</lpage> </nlm-citation> </ref> <ref id="ref17"> <label>17</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Assadi</surname> <given-names>F</given-names> </name> </person-group> <article-title>The epidemic of pediatric chronic kidney disease: The danger of skepticism.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>61</fpage> <lpage>4</lpage> </nlm-citation> </ref> <ref id="ref18"> <label>18</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Khajehdehi</surname> <given-names>P</given-names> </name> </person-group> <article-title>Turmeric: Reemerging of a neglected Asian traditional remedy.J Nephropathology</article-title> <source></source> <year>2012</year> <volume>1</volume> <fpage>17</fpage> <lpage>22</lpage> </nlm-citation> </ref> <ref id="ref19"> <label>19</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Kang</surname> <given-names>DH</given-names> </name> <name> <surname>Yu</surname> <given-names>ES</given-names> </name> <name> <surname>Yoon</surname> <given-names>KI</given-names> </name> <name> <surname>Johnson</surname> <given-names>R</given-names> </name> </person-group> <article-title>The impact of gender on progression of renal disease: Potential role of estrogen-mediated vascular endothelial growth factor regulation and vascular protection</article-title> <source>Am J Pathol</source> <year>2004</year> <volume>164</volume> <fpage>679</fpage> <lpage>88</lpage> </nlm-citation> </ref> <ref id="ref20"> <label>20</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Ghorbani</surname> <given-names>A</given-names> </name> </person-group> <article-title>Renal protective effect of selenium on cisplatin-induced nephrotoxicity</article-title> <source>J Ren Inj Prev</source> <year>2012</year> <volume>1</volume> <fpage>31</fpage> <lpage>2</lpage> </nlm-citation> </ref> <ref id="ref21"> <label>21</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"></person-group> <article-title></article-title> <source></source> <year></year> <volume></volume> <fpage></fpage> </nlm-citation> </ref> </ref-list> </back> </article>