Ultrastructural organization of hemomicrocirculatory bed of the lungs affected by Doxorubicin

Abstract

One of the most effective anticancer drugs for breast cancer, lymphoma, soft tissue sarcoma, leukemia, some solid tumors is Doxorubicin. However, its antitumor effect directly correlates with the dose-dependent manifestation of toxicity to healthy tissues and body systems. The purpose of the study is to study the dynamics of ultrastructural changes of the hemomicrocirculatory bed under the influence of Doxorubicin. Animals were divided into 3 groups: I – intact rats (n=10); II – control (n=20); III – rats with Doxorubicin model (n=40). Doxorubicin was administered intraperitoneally at a dose of 5 mg/kg body weight once a week for 4 weeks. An animal control group was intraperitoneally injected with an equivalent volume of saline. Pulmonary tissue sampling for electron microscopic examination was performed under thiopental anesthesia 7, 14, 21, 28 days after the start of the experiment. Pieces of pulmonary tissue were fixed in 2.5% glutaraldehyde followed by fixation in 1% osmium tetroxide. After dehydration, the material was poured into araldite-epon. The sections obtained on a “Tesla BS-490” ultramicrotome were examined in an electron microscope “PEM-125K”. It is established that within 7 days after the first injection of Doxorubicin in the lungs changes in the structural organization of the hemomicrocapillary bed and the disturbance of blood rheological properties are determined, as evidenced by the excessive accumulation of neutrophils in the hemocapillaries, their adhesion and aggregation. With the extension of the study period (14-28 days) there is a progressive disturbance of the submicroscopic structure of hemocapillaries of the alveolar wall and marked changes in the rheological properties of blood. In endothelial cells, swelling phenomena with organelle disorganization are determined, and in some areas there is a desquamation of endothelial cells into the lumen of the hemocapillaries with basal membrane exposures. In the lumen of the microvessels, red blood cells and leuco-platelet aggregates are noted. Thus, the introduction of Doxorubicin leads to pronounced submicroscopic changes in the hemomicrocirculatory bed. Violation of the ultrastructural organization of the hemomicrocirculatory bed of the lungs is determined after 7 days after the start of the study.