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  <front>
    <journal-meta>
      <journal-id journal-id-type="pmc">JRMS</journal-id>
      <journal-id journal-id-type="pubmed">J Res Med Sci</journal-id>
      <journal-id journal-id-type="publisher-id">Journal of Research in Medical Sciences</journal-id>
      <journal-title>Journal of Research in Medical Sciences</journal-title>
      <issn pub-type="ppub">1735-1995</issn>
      <issn pub-type="epub">1735-7136</issn>
      <publisher>
        <publisher-name>Medknow Publications Pvt Ltd</publisher-name>
        <publisher-loc>India</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">JRMS-18-1119</article-id>
      <article-id pub-id-type="pmid">24523810</article-id>
      <article-categories>
        <subj-group subj-group-type="headings">
          <subject>Commentary</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Comment on: A model for prediction of cisplatin induced nephrotoxicity by kidney weight in experimental rats</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Nasri</surname>
            <given-names>Hamid</given-names>
          </name>
          <xref ref-type="aff" rid="aff1" />
          <xref ref-type="corresp" rid="cor1" />
        </contrib>
      </contrib-group>
      <aff id="aff1">Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran</aff>
      <author-notes>
        <corresp id="cor1">
        <bold>Address for correspondence:</bold>Hamid Nasri, Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran 
        <email xlink:href="hamidnasri@med.mui.ac.ir">hamidnasri@med.mui.ac.ir</email></corresp>
      </author-notes>
      <pub-date pub-type="ppub">
        <season>December</season>
        <year>2013</year>
      </pub-date>
      <volume>18</volume>
      <issue>12</issue>
      <fpage>1119</fpage>
      <lpage>1120</lpage>
      <history>
        <date date-type="received">
          <day>5</day>
          <month>6</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>28</day>
          <month>7</month>
          <year>2013</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Copyright: &#x000a9; Journal of Research in Medical Sciences</copyright-statement>
        <copyright-year>2013</copyright-year>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0">
          <p>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>
        </license>
      </permissions>
      <abstract>
        <p>Cisplatin (cis-diamminedichloroplatinum II), as one of the most applicable and potent anticancer medication, is used in the treatment of a various pediatric and adult malignancies. However, it gives side-effects such as renal toxicity which is dose-dependent, and thus limited its usage. Treatment with cisplatin induces the inflammatory mechanisms, which leads to a reduction in the antioxidant levels, leading to a failure of the antioxidant protection against free-radical damage generated by antitumor drugs. The oxidative stress, induced by cisplatin in the kidney was partially inhibited by antioxidant therapy using selenium, glutathione, flavonoids, and superoxide dismutase.</p>
      </abstract>
      <kwd-group>
        <kwd>Cisplatin</kwd>
        <kwd>kidney</kwd>
        <kwd>nephrotoxicity</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title />
      <p>Cisplatin (cis-diamminedichloroplatinum II), as one of the most applicable and potent anticancer medication, is used in the treatment of a various pediatric and adult malignancies. 
      <sup>
        <xref ref-type="bibr" rid="ref1">1</xref>
      </sup>However, it gives side-effects such as renal toxicity which is dose-dependent, and thus limited its usage. 
      <sup>
        <xref ref-type="bibr" rid="ref1">1</xref>
      </sup>,
      <sup>
        <xref ref-type="bibr" rid="ref2">2</xref>
      </sup>Treatment with cisplatin induces the inflammatory mechanisms, which leads to a reduction in the antioxidant levels, leading to a failure of the antioxidant protection against free-radical damage generated by antitumor drugs. The oxidative stress, induced by cisplatin in the kidney was partially inhibited by antioxidant therapy using selenium, glutathione, flavonoids, and superoxide dismutase. 
      <sup>
        <xref ref-type="bibr" rid="ref2">2</xref>
      </sup>,
      <sup>
        <xref ref-type="bibr" rid="ref3">3</xref>
      </sup>,
      <sup>
        <xref ref-type="bibr" rid="ref4">4</xref>
      </sup>,
      <sup>
        <xref ref-type="bibr" rid="ref5">5</xref>
      </sup>Therefore various agents, containing herbal and chemical drugs have been tested to find their efficacy to reduce cisplatin-induced nephrotoxicity. 
      <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>,
      <sup>
        <xref ref-type="bibr" rid="ref4">4</xref>
      </sup>,
      <sup>
        <xref ref-type="bibr" rid="ref5">5</xref>
      </sup>The renal toxicity effects of cisplatin are demonstrated by a decrease in creatinine clearance and electrolyte disturbances, mainly hypomagnesemia, largely due to the acute cytotoxic effects of cisplatin on distal and proximal tubules. 
      <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>,
      <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>There were two points that should be remembered form the study of Ashrafi, et al. 
      <sup>
        <xref ref-type="bibr" rid="ref7">7</xref>
      </sup>Firstly, in recent years much attention has been directed towards the gender difference in cisplatin renal toxicity. 
      <sup>
        <xref ref-type="bibr" rid="ref8">8</xref>
      </sup>Indeed, there are sharp sex-dependent differences in reaction rates and the probability of side effects in individuals treated with chemotherapy. Gender-biased expression levels of metabolic enzymes and transporters in kidney directing to different pharmacokinetics have been explained for most common anticancer drugs. 
      <sup>
        <xref ref-type="bibr" rid="ref8">8</xref>
      </sup>It was found that in female gender drug half-life is often longer, which is associated with improved survival, but also increased toxicity. Secondly, in the study conducted by Ashrafi et al., normalized kidney weight and morphological damage scores has been proposed to be is an acceptable predictor of kidney function in cisplatin-induced renal toxicity in experimental rats. 
      <sup>
        <xref ref-type="bibr" rid="ref7">7</xref>
      </sup>However, a variety of novel urinary biomarkers have been recognized and partially qualified for use as the markers for kidney damage in rats with acute kidney injury. 
      <sup>
        <xref ref-type="bibr" rid="ref9">9</xref>
      </sup>These novel biomarkers are lipocalin-2, glutathione S-transferase-yb1 (GSTYb1), osteopontin, renal papillary antigen 1 (RPA-1) and urinary albumin, alpha glutathione s-transferase (&#945;-GST), kidney injury molecule-1 (KIM-1), and plasma cystatin C; alongside the traditional biomarkers of plasma creatinine, urea, urinary total protein, glucose, and n-acetyl-beta-d-glucosaminidase (NAG). 
      <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>,
      <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>,
      <sup>
        <xref ref-type="bibr" rid="ref9">9</xref>
      </sup>Hence in the near future, some of these urinary biomarkers may be suggested to more precisely show the cisplatin kidney toxicity and accepted as the biomarkers of cisplatim renal injury. 
      <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>,
      <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>,
      <sup>
        <xref ref-type="bibr" rid="ref9">9</xref>
      </sup>,
      <sup>
        <xref ref-type="bibr" rid="ref10">10</xref>
      </sup>,
      <sup>
        <xref ref-type="bibr" rid="ref11">11</xref>
      </sup>It should be pointed out that, investigations regarding gender difference in cisplatin renal injury is scarce and more investigations needs to find the clinical significance of gender on renal injury induced by cisplatin. Also, more study on the biomarkers of acute kindly injury during cisplatin toxicity suggests to better find the acute kidney injury of cisplatin and effectively abolishes damages to the kidneys and decrease morbidity of these patients. 
      <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="ref9">9</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></p>
    </sec>
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