EN
The ability to control the phenomenon of apoptosis, its induction or inhibition, raises hopes for treating many diseases including cancer. Adriamycin, an antibiotic that is wildly used after treating cancer, induces apoptosis in liver cells in a certain and relatively quick way after its application. The aim of the work was to obtain and examine the model of apoptosis and necrosis of hepatocytes with respect to their response to different damaging stimuli (adriamycin) depending on the time after the application in correlation with the ultrastructural construction, which is the result of the different location of hepatocytes within the portal acinus (of Rappaport). There were 32 female white Wistar rats used in the study. They were divided into 4 groups (2 experimental and 2 control), 8 animals in each group. The adriamycin dose of 5 mg/kg was administered intraperitoneally to the rats in groups I and II and then the rats were decapitated after 4 weeks (group I) and after 8 weeks (group II). The rats in the control groups were given 0.5 ml 0.9% NaCl solution and then decapitated after 4 weeks (group III) and 8 weeks (group IV). In the research, preparations made from fragments of the right liver lobe were used for histological observations and immunohistochemical studies. In the immunohistochemical studies, a three-stage method was used. According to this method, hepatocytes were examined qualitatively and quantitatively for the presence of proteins involved in apoptosis, to which the death signals run: through mitochondrial pathways (caspase 3 and caspase 9), through intrinsic pathways by endoplasmic reticulum (caspase 3 and caspase 12), through extrincic pathways (caspase 3 and caspase 8) and one from inflammatory markers: caspase 1. Histological images showed that the apoptosis phenomenon occurs after the administration of adriamycin in hepatocytes in a zonate way and is dependent on the time that has elapsed since its administration. Immunohistochemical studies showed, in both a qualitative and quantitative way, a phenomenon of apoptosis in hepatocytes (executive caspase 3) and necrosis (caspase 1). It was also proved that the signal for the induction of apoptosis showed zonation and mainly followed the mitochondrial pathway (caspase 9); the intrinsic pathway by endoplasmic reticulum was much less common (caspase 12); while even more rarely caspase 8 was identified as a marker of an extrinsic pathway to induce apoptosis.