<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>2444-054X</journal-id>
<journal-title><![CDATA[Cirugía y cirujanos]]></journal-title>
<abbrev-journal-title><![CDATA[Cir. cir.]]></abbrev-journal-title>
<issn>2444-054X</issn>
<publisher>
<publisher-name><![CDATA[Academia Mexicana de Cirugía A.C.]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S2444-054X2025000500011</article-id>
<article-id pub-id-type="doi">10.24875/ciru.25000020</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Rosmarinic acid alleviate hepatotoxicity induced by cyclophosphamide in rats]]></article-title>
<article-title xml:lang="es"><![CDATA[El ácido rosmarínico alivia la hepatotoxicidad inducida por ciclofosfamida en ratas]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Uçar-Ekin]]></surname>
<given-names><![CDATA[Cemre]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[A&#351;&#305;r]]></surname>
<given-names><![CDATA[F&#305;rat]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[&#350;ahin]]></surname>
<given-names><![CDATA[F&#305;rat]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Kaplan]]></surname>
<given-names><![CDATA[&#350;ehmus]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Dicle University Faculty of Medicine Department of Physiology]]></institution>
<addr-line><![CDATA[Diyarbak&#305;r ]]></addr-line>
<country>Turkey</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Dicle University Faculty of Medicine Department of Histology and Embryology]]></institution>
<addr-line><![CDATA[Diyarbak&#305;r ]]></addr-line>
<country>Turkey</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>10</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>10</month>
<year>2025</year>
</pub-date>
<volume>93</volume>
<numero>5</numero>
<fpage>546</fpage>
<lpage>555</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_arttext&amp;pid=S2444-054X2025000500011&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_abstract&amp;pid=S2444-054X2025000500011&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.mx/scielo.php?script=sci_pdf&amp;pid=S2444-054X2025000500011&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract  Objective: This study aimed to investigate the hepatoprotective effects of Rosmarinic acid (RA) against cyclophosphamide (CP)-induced liver injury in rats.  Methods: Twenty-one male Wistar Albino rats were divided into three groups: Control, CP, and CP + RA. Hepatotoxicity was induced by administering CP (20 mg/kg/day) intraperitoneally for 14 days. RA (20 mg/kg/day) was administered for 14 days after CP induction. Serum biochemical parameters including malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. Liver tissues underwent histological and immunohistochemical analysis for B-cell lymphoma 2 (Bcl-2), apoptotic protease activating factor 1 (Apaf-1), nuclear factor erythroid 2-related factor 2 (Nrf-2), and tumor necrosis factor (TNF)-&#945;. In addition, in silico analysis was performed to explore potential molecular targets of RA and their biological pathways.  Results: CP significantly increased liver weight, MDA content, ALT and AST enzyme activities, indicating hepatic oxidative stress and injury. Histologically, CP caused severe hepatocellular damage characterized by hepatocyte degeneration, hemorrhage, and disrupted hepatic architecture. Immunohistochemically, CP exposure upregulated pro-apoptotic (Apaf-1), oxidative stress (Nrf-2), and inflammatory (TNF-&#945;) markers, while downregulating anti-apoptotic (Bcl-2) proteins. RA administration significantly reversed these biochemical and histopathological changes. In silico analysis revealed RA interacts with multiple inflammatory and oxidative stress pathways, reinforcing its hepatoprotective role.  Conclusion: RA demonstrates significant hepatoprotective activity against CP-induced liver toxicity by attenuating oxidative stress, inflammation, and apoptosis pathways. RA represents a promising therapeutic agent to manage drug-induced hepatotoxicity.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen  Objetivo: Investigar los efectos hepatoprotectores del ácido rosmarínico (AR) frente a la lesión hepática inducida por ciclofosfamida (CP) en ratas.  Métodos: Se dividieron 21 ratas macho Wistar Albino en tres grupos: control, CP y CP + AR. La hepatotoxicidad fue inducida administrando CP (20 mg/kg/día) por vía intraperitoneal durante 14 días. Posteriormente se administró AR (20 mg/kg/día) durante 14 días. Se midieron parámetros bioquímicos séricos incluyendo malondialdehído (MDA), alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Se realizaron análisis histológicos e inmunohistoquímicos en tejidos hepáticos para Bcl-2, Apaf-1, Nrf-2 y TNF-&#945;. Además, se realizó un análisis in silico para explorar posibles dianas moleculares del AR y sus vías biológicas relacionadas.  Resultados: El CP incrementó significativamente el peso hepático, el contenido de MDA y las actividades de ALT y AST, indicando estrés oxidativo y lesión hepática. Histológicamente, el CP causó daño hepatocelular grave caracterizado por degeneración hepatocitaria, hemorragia y arquitectura hepática alterada. Inmunohistoquímicamente, la exposición al CP aumentó los marcadores proapoptóticos (Apaf-1), de estrés oxidativo (Nrf-2) e inflamatorios (TNF-&#945;), y disminuyó las proteínas antiapoptóticas (Bcl-2). La administración de AR revirtió de manera significativa estos cambios bioquímicos e histopatológicos. El análisis in silico reveló que el AR interactúa con múltiples vías inflamatorias y de estrés oxidativo, fortaleciendo su rol hepatoprotector.  Conclusione: El AR mostró actividad hepatoprotectora significativa contra la toxicidad hepática inducida por CP, atenuando las vías de estrés oxidativo, inflamación y apoptosis. El AR representa un agente terapéutico prometedor para manejar la hepatotoxicidad inducida por fármacos.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Apoptosis]]></kwd>
<kwd lng="en"><![CDATA[Cyclophosphamide]]></kwd>
<kwd lng="en"><![CDATA[Hepatotoxicity]]></kwd>
<kwd lng="en"><![CDATA[Inflammation]]></kwd>
<kwd lng="en"><![CDATA[Oxidative stress]]></kwd>
<kwd lng="es"><![CDATA[Apoptosis]]></kwd>
<kwd lng="es"><![CDATA[Ciclofosfamida]]></kwd>
<kwd lng="es"><![CDATA[Hepatotoxicidad]]></kwd>
<kwd lng="es"><![CDATA[Inflamación]]></kwd>
<kwd lng="es"><![CDATA[Estrés oxidativo]]></kwd>
</kwd-group>
</article-meta>
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