Morphological Characteristics of the Liver and Immunohistochemical Analysis of HSP70 Expression in Hepatocytes under the Impact of Doxorubicin and Rosuvastatin.

Abstract

A morphological and immunohistochemical analyses of the liver of male WAG rats (n=47) were performed after isolated and combined administration of doxorubicin and rosuvastatin. Doxorubicin (7 mg/kg) was administered intraperitoneally once, while rosuvastatin (10 mg/kg) was given intragastrically daily; the animals were euthanized after 4, 14, and 21 days of experiment. The main morphological changes observed in the liver after both isolated doxorubicin administration and in combination with rosuvastatin included dystrophic and necrobiotic changes in hepatocytes, uneven congestion with the formation of thrombotic masses in the portal vein system, and pronounced perivenous edema. Isolated administration of rosuvastatin led to severe dystrophic changes in hepatocytes and fewer circulatory disturbances in the form of vascular congestion. Immunohistochemical analysis revealed nuclear, cytoplasmic, and mixed (nuclear-cytoplasmic) localization of HSP70 in hepatocytes in all experimental groups. In the liver of control rats, mixed localization of HSP70 significantly prevailed (>62% of hepatocytes; p<0.001); only nuclear localization was found in 9% of cells. When doxorubicin and rosuvastatin were administered alone or in a combination, significant translocation of HSP70 from the cytoplasm to the nucleus occurred (the index of hepatocytes with HSP70 localization in the nuclei increase by 3-4.5 times), which may reflect the cytotoxic nature of these drugs and the activation of cytoprotective mechanisms.