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EN
Adriamycin (ADR) – the antineoplastic antibiotics has confirmed proapoptotic activity, mainly on neoplastic cells and young quick dividing cells. Cardiotoxicity of Adriamycin is limitating in antineoplastic therapy. The purpose of study was an evaluation of internal pathway of induction of signal to the apoptosis in myocardial cells of rat, which had administered Adriamycin. The sign of late cardiotoxicity after Adriamycin is coagulative necrosis. In present study was noticed also increased apoptosis of cells in rat heart, which was induced via mitochondrial pathway, with activation of p-53 protein and with BAX/Bcl-2 ratio > 1 – with prevalence of proapoptotic BAX protein.
EN
The study was performed on 16 albino Wistar female rats divided into two equal groups: experimental and control. The rats from the experimental group received per os, every second day for 2 weeks 40 mg/kg b.w. of L-arginine. The rats from the control group received, in the same manner, 2 ml of distilled water. The animals were decapitated after 3 weeks of the experiment. After decapitation specimens from the kidneys were collected, fixed in 10% formalin, and then embedded in paraffin blocks. Protein caspase 3 was detected using the standard three step immunohistochemical method. Additionally, the apoptotic index was evaluated. The study shows that L-arginine, as a donor of exogenous nitric oxide, induced the apoptotic signal in normal renal tubular cells of the rats. The apoptotic index statistically significantly increased in the epithelial cells of the treated renal tubules compared to the control. The immunohistochemical reaction for the executing caspase 3 in the renal tubular cells, although increased in comparison with the control, was statistically insignificant.
EN
The presented study describes renal tubular epithelial cells morphology in rats during adriamycin therapy. It was demonstrated that one dose of the compound can induce increasing-with time-apoptosis in the cells. A statistically-significant increase in the number of apoptotic cells was observed in experimental groups compared to controls. The highest percentage of apoptotic cells was found in rats 7 weeks after adriamycin administration. The number of apoptotic cells in these animals was statistically significantly higher than that in the rats 4 weeks after adriamycin administration.
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.
EN
In previous papers, we noticed that adriamycin given to female rats before their planned pregnancy has a delaying effect under the form of apoptosis for foetal hepatocytes. The purpose of present study was for a quantitative assessment of foetal renal tubular epithelial cells, as an effect means of delaying adriamycin action (apoptotic index). Expression of effector caspase 3 was also assessed. In the investigations, a standard three-step immunohistochemical method was used. The area covered by positive caspase 3 reaction was examined. In the kidneys of foetuses from the experimental group, we noticed an increase in the apoptotic index; furthermore, immunohistochemical reaction for caspase 3 covered a statistically significantly larger range as compared to the control group. The delayed effect of adriamycin, which was given to female rats before pregnancy, was an increase in apoptosis in foetal renal tubular epithelial cells.
EN
Adriamycin is an antineoplastic antibiotic which is biodegragated mainly in the liver. The purpose of this study was to analyse the apoptotic index and the histological structure of apoptotic cells in the rat liver. Rats were examined 4 and 7 weeks after adriamycin treatment. The animals were divided into four equal groups: groups I and III, consisting of rats treated with a single intraperitoneal dose of adriamycin (5 mg/kg b.w) and decapitated after 4 or 7 weeks; groups II and IV comprising control rats treated with a single intraperitoneal dose of 0.9% NaCl (0.5 ml) and decapitated after 4 or 7 weeks. After decapitation, liver specimens were collected and embedded in paraffin. Slides were stained with haematoxylin and eosin. The degree of apoptosis was determined quantitatively using the apoptotic index. Statistical analysis was performed using the one-way ANOVA test and Student’s t-test. A single dose of adriamycin induced apoptosis of hepatocytes, which increased with time The apoptotic index was significantly higher in the group examined 7 weeks after adriamycin administration. The histological structure of the liver in the experimental groups was similar. The lesions observed were focal. The blurring of the hepatic cell membrane and a focal disintegration of architectonics concerning the shape and size of hepatocytes were visible. Chromatin in the nuclei was dispersed. Some nuclei showed peripheral chromatin condensation. The cytoplasm of some cells showed numerous vacuoles. Naked nuclei and congestion resulting from vessel damage were visible.
EN
Sixteen white Wistar female rats were divided into two equal groups. Experimental group received per os 40 mg/kg b.w. of L-arginine, even other day for 2 weeks and were decapitated after 3 weeks of the experiment. Control rats received in the same manner 2 ml of distilled water and were decapitated after 3 weeks of the experiment. The renal lesions observed under electron microscope were of focal character and concerned only the experimental group. The tubules with necrotic cells were observed among normal tubules or single normal epithelial cells of the tubular wall. The boundaries between epithelial cells of the tubule wall were blurred. The mitochondria indicated abnormal structure. Numerous hsosomes and peroxisomes with dark, homogenous content were observed. The rough endoplasmic reticulum had widened channels and was focally completely destroyed. The nucleus of damaged cells was most commonly located in one of the cell poles; its shape was changed and visibly smaller than the nuclei of normal cells. Condensation and peripherally located chromatin were noticed. The lesions observed were characteristic for apoptotic cells.
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