Comprehensive assessment of subchronic low-dose exposure to doxorubicin in the Wistar rat model

Rationale. Doxorubicin is a chemotherapeutic antibiotic from the anthracycline class that has cumulative and dose-dependent cardiotoxic effects. The cardiotoxic properties of doxorubicin are manifested in characteristic pathologies of the heart and its microenvironment. Doxorubicin also exhibits genotoxic properties and is often used to model acute genotoxic effects in small laboratory animal models.

Aim: To evaluate chronic low-dose exposure to doxorubicin in a Wistar rat model using cytogenetic methods and electron microscopy.

Material and Methods. The study included two groups of 10 male Wistar rats: an experimental group (weekly doxorubicin in the tail vein 2 mg/kg for 4 weeks) and a control group (0.9% NaCl). A micronucleus test was used to evaluate genotoxic effects. Visualization of the myocardial structure was carried out using scanning electron microscopy in back-scattered electrons on an electron microscope.

Results. The analysis showed a significant difference between the control (0.8%) and experimental groups (3.2%) in the level of polychrome erythrocytes with a micronucleus. It was found that rats from the experimental group were characterized by a significant decrease in the number of polychromatic red blood cells compared to the control group. In the experimental group, pronounced heterogeneity of the morphological structure of the myocardium was noted. Electron micrographs of hepatocytes from rats treated with doxorubicin showed degenerative changes in the structure of liver cells.

Conclusion. The results of our study provide insight into the subacute effect of a small dose of doxorubicin on the heart, liver and hematopoietic system of normolipidemic Wistar rats. We have proposed mechanisms of interaction between important organs and systems of the body exposed to doxorubicin against the background of a general pathological condition. In the future, the nature of the toxic effects of lower and optimal doses of the mutagen in the context of subchronic cumulative exposure should be determined.

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