biostudies-literatureNicol MFondation de France8104https://www.ebi.ac.uk/biostudies/studies/S-EPMC11890863biostudies-literatureUnknown15(1)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.Scientific reportsStreptozotocin-induced hyperglycemia unmasks cardiotoxicity induced by doxorubicin.PMC118908632019 00086501Genest MAzibani FPolidano ESamuel JLAssad NNicol MRahli RDeniau BMebazaa ASolal ACfalseStreptozotocin-induced hyperglycemia unmasks cardiotoxicity induced by doxorubicin.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.2025-01-01T00:00:00Z2025 Mar2025-04-04T08:23:24.8Z2025-04-04T08:23:24.8ZS-EPMC118908634005754610.1038/s41598-025-91824-0