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<p>Late-onset cardiotoxicity induced by anthracyclines occurs years to decades after completion of anti-cancer therapy and is associated with increased morbi-mortality of cancer survivors. Chemotherapy at the time of treatment probably causes cardiac damages for which the juvenile heart compensate. Co-morbidities happening in the adulthood such as type 1 diabetes (DT1), affect the heart and thus can unmask chemotherapy induced cardiotoxicity. To prove our hypothesis, we induced hyperglycemia [Streptozotocin treatment (STZ), 50&#xa0;mg/kg/day for 5 days] in 11 weeks old mice who previously received doxorubicin treatment (Dox, 3 mg/kg) when they were six-weeks old. Interestingly, streptozotocin-induced hyperglycemia in Dox-pretreated mice (Dox-STZ) induced a higher mortality (<i>p</i> &lt; 0.05) and more severe cardiac dysfunction (<i>p</i> &lt; 0.0001) when compared with mice receiving Dox or STZ alone. Apoptosis evaluated by caspase 3 protein expression and <i>Bax</i>/<i>Bcl2</i> genes expression was higher in Dox-STZ mice compared to STZ or Dox alone. While Dox and STZ independently induced capillary rarefaction, cardiomyocytes atrophy was only induced by STZ. Furthermore, Sirius-red staining of cardiac sections showed higher fibrosis levels (<i>p</i> &lt; 0.0001) in Dox-STZ compared to Dox or STZ alone. All together, these results demonstrate that STZ precipitates and unmask cardiac dysfunction in previously treated Dox animals.</p>

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Streptozotocin-induced hyperglycemia unmasks cardiotoxicity induced by doxorubicin

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月8日

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  • Martin Nicol,
  • Benjamin Deniau,
  • Roza Rahli,
  • Magali Genest,
  • Evelyne Polidano,
  • Noma Assad,
  • Jane-lise Samuel,
  • Alexandre Mebazaa,
  • Alain Cohen Solal,
  • Feriel Azibani

摘要

Late-onset cardiotoxicity induced by anthracyclines occurs years to decades after completion of anti-cancer therapy and is associated with increased morbi-mortality of cancer survivors. Chemotherapy at the time of treatment probably causes cardiac damages for which the juvenile heart compensate. Co-morbidities happening in the adulthood such as type 1 diabetes (DT1), affect the heart and thus can unmask chemotherapy induced cardiotoxicity. To prove our hypothesis, we induced hyperglycemia [Streptozotocin treatment (STZ), 50 mg/kg/day for 5 days] in 11 weeks old mice who previously received doxorubicin treatment (Dox, 3 mg/kg) when they were six-weeks old. Interestingly, streptozotocin-induced hyperglycemia in Dox-pretreated mice (Dox-STZ) induced a higher mortality (p < 0.05) and more severe cardiac dysfunction (p < 0.0001) when compared with mice receiving Dox or STZ alone. Apoptosis evaluated by caspase 3 protein expression and Bax/Bcl2 genes expression was higher in Dox-STZ mice compared to STZ or Dox alone. While Dox and STZ independently induced capillary rarefaction, cardiomyocytes atrophy was only induced by STZ. Furthermore, Sirius-red staining of cardiac sections showed higher fibrosis levels (p < 0.0001) in Dox-STZ compared to Dox or STZ alone. All together, these results demonstrate that STZ precipitates and unmask cardiac dysfunction in previously treated Dox animals.