All anthracyclines, including doxorubicin (DOXO), the most common and still indispensable drug, exhibit cardiotoxicity with inherent risk of irreversible cardiomyopathy leading to heart failure with reduced ejection fraction (HFrEF). Current pharmacological strategies are clearly less effective for this type of HFrEF, hence an urgent need for new therapeutic approaches. The prerequisite for success is thorough understanding of pathophysiology of this HFrEF form, which requires an appropriate animal model of the disease. The aim of this study was to comprehensively characterise a novel model of HF with cardiorenal syndrome, i.e. DOXO-induced HFrEF with nephrotic syndrome, in which DOXO was administered to Ren-2 transgenic rats (TGR) via five intravenous injections in a cumulative dose of 10 mg/kg of body weight (BW). Our analysis included survival, echocardiography, as well as histological examination of the heart and kidneys, blood pressure, but also a broad spectrum of biomarkers to evaluate cardiac remodelling, fibrosis, apoptosis, oxidative stress and more. We have shown that the new model adequately mimics the cardiac remodelling described as "eccentric chamber atrophy" and myocardial damage typical for DOXO-related cardiotoxicity, without major damage of the peritoneum, lungs and liver. This pattern corresponds well to a clinical situation of cancer patients receiving anthracyclines, where HF develops with some delay after the anticancer therapy. Therefore, this study may serve as a comprehensive reference for all types of research on DOXO-related cardiotoxicity, proving especially useful in the search for new therapeutic strategies.

• Klíčová slova
• Chemotherapy induced heart failure, Doxorubicin, Experimental model of heart failure, NO/sGC/cGMP pathway, Ren-2 transgenic hypertensive rat,
• MeSH
• doxorubicin * škodlivé účinky   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   patofyziologie   MeSH
• modely nemocí na zvířatech * MeSH
• nefrotický syndrom * chemicky indukované   farmakoterapie   patofyziologie   MeSH
• oxidační stres účinky léků   MeSH
• potkani transgenní * MeSH
• protinádorová antibiotika škodlivé účinky   MeSH
• srdeční selhání * chemicky indukované   patofyziologie   MeSH
• tepový objem * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• doxorubicin * MeSH
• protinádorová antibiotika MeSH