Key result
Serial intravesical administration of Doxorubicin at 5 mg/kg weekly for 5 weeks caused mild morphological changes in the rat myocardium, including interstitial edema and focal fibrosis.
Why the study?
Doxorubicin causes systemic cardiotoxicity, prompting the search for preventive administration strategies such as intravesical delivery.
Does intravesical administration of Doxorubicin cause cardiotoxic morphological changes in female Wistar rats?
Does intravesical administration of Doxorubicin cause cardiotoxic morphological changes in female Wistar rats?
Serial intravesical administration of Doxorubicin in rats causes morphological changes in the myocardium indicative of cardiotoxicity, though less pronounced than systemic administration.
Intravesical doxorubicin induces milder myocardial changes than systemic dosing in rats; leaves open whether this route meaningfully reduces clinical cardiotoxicity.
Along with a pronounced antitumor effect, Doxorubicin causes systemic effects with damage to vital organs, including the heart. It prompts the search for ways to prevent the cardiotoxic effect of the drug, one of which could be its intravesical administration. The aim of the study was to develop a method of serial intravesical administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received intravesical chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysium). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During intravesical chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data partially indicate the development of dilated cardiomyopathy in experimental animals. However, these changes were less pronounced than the previously described changes that occur after systemic administration of the drug. Additional studies of the electrophysiological activity of the heart and biochemical markers will make it possible to fully assess the degree of cardiotoxicity of Doxorubicin after its intravesical administration. Thus, serial intravesical administration of Doxorubicin in moderate therapeutic doses according to the proposed method causes changes in the myocardium of experimental animals, which are partially similar to the changes in the heart of people receiving chemotherapy with this drug.
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Kostiuk et al. (2021) studied Doxorubicin-induced cardiotoxicity (n=42). Doxorubicin vs. Intact control group was evaluated on Morphological changes in the myocardium (cardiomyocyte diameter, nuclear diameter, interstitial space width). Serial intravesical administration of Doxorubicin at 5 mg/kg weekly for 5 weeks caused mild morphological changes in the rat myocardium, including interstitial edema and focal fibrosis.
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