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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2023; 69(6): 3-14


M.V. Denysova, N.A. Strutynska, L.A. Mys, Yu.P. Korkach, K.V. Rozova, V.F. Sagach

    Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine


Doxorubicin is a potent cytotoxic antibiotic that is the most widely prescribed in the world and is effective against a wide range of cancers. At the same time, the cardiotoxic effects of this drug often require discontinuation of treatment before the effect is achieved. Mitochondria are important mediators of cellular life, and cardiomyocyte death due to mitochondrial mechanisms of internal killing is the basis of many heart diseases. The aim of the study was to investigate the effects of short-term doxorubicin administration on Ca2+-induced opening of the nonspecific mitochondrial permeability transition pore (mPTP) in the heart of adult rats. To reproduce and evaluate acute cardiotoxicity in rats, which is the main complication in patients taking doxorubicin, a short-term doxorubicin cardiomyopathy model was used. A comparative ultrastructural study of myocardial tissues was performed at total cumulative doses of doxorubicin of 8, 13 and 15 mg/kg administered intraperitoneally and spread over two days. It was shown that the drug caused damage and death of the myofibrillar apparatus, mitochondria and cardiomyocytes and exhibited a dose-dependent effect. Therefore, further experiments were carried out at the most indicative dose, namely 15 mg/kg. We have shown that the content of reactive oxygen species in the heart mitochondria, namely, •O2-, Н2О2, •ОН, increased after doxorubicin administration by 10.5, 5.3 and 3.4 times, respectively, indicating a significant increase in free radical processes. It is important that at the same time, the content of endogenous H2S decreased by 2.6 times. This activated mPTP opening in the rat heart: the amplitude of spontaneous swelling doubled, Ca2+-induced swelling increased by 53% compared to the control, and an increase in mPTP sensitivity to Ca2+ was observed at all applied concentrations. Thus, the acute cardiotoxic effect of doxorubicin resulted in the induction of mPTP opening, which led to mitochondrial and cardiomyocyte death.

Keywords: doxorubicin; nonspecific mitochondrial permeability transition pore; mitochondria; cardiomyocytes; cardiomyopathy


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