Being a serious adverse effect of chemotherapy, toxicity, especially hepatotoxicity with 18.9% prevalence is one of the most common reasons of treatment refusal. The purpose of the study was to investigate the histological structure under the influence of anti–tumor drugs paclitaxel and cisplatin after their intraperitoneal administration. Material and methods. 25 white rats were injected intraperitoneally with Paclitaxel, the dose being 0.1 mg of active substance in 0.5 ml of 0.9% NaCl, according to the method suggested by R. S. Rolomano et al. (2001). Cisplatin was injected intraperitoneally to 23 animals, the dose being 2 mg to each kg of body mass. The injections were conducted during 9 weeks once a week. Results and discussion. In the experiment, the maintenance of the rats and all manipulations over them were conducted in compliance with bioethical requirements. Animals were removed from the experiment by degradation using ethereal anesthesia. The experiment terms were set to be 1, 7, 14, 21 and 28 days. The animals were desensitized with etheric anesthesia according to the standard. The results proved for the strong effect of Paclitaxel. On the 1st–7th days hepatocytes differed from each other in shape and size. The vast majority of hepatocytes were deformed. On the 14th day the signs of reactive hepatitis increased. Disorganization of various hepatic cords was ubiquitous and widened in each part of the peripheral sections in direction to central ones. In emerging hepatocytes, vacuoles were often prone to unite into large vacuoles. The nuclei contained mitosis figures, the number of double–nucleated hepatocytes increased. There appeared new capillaries in the vascular pattern of hepatic lobules (lobules "capillary"). The edema increased in portal triads. At a later stage (28 days) the number of hepatocytes with lipid vacuoles also increased. Their mitotic activity was reduced. Intralobular lympho–plasmocytic infiltrates were identified. With prolonged administration of cisplatin (once a week, 9 weeks) within 7 days after the last injection, hepatic histological structure disorders were observed, the shape of hepatocytes became rounded. In some hepatocytes, a weak eosinophilic staining was detected, some containing an optically hollow cytoplasm. Violation of the vascular pole of hepatocytes was observed. The vascular pattern of the liver lobe was characterized by hyperemia, sinusoids and central veins were enlarged. On the 14th day of the experiment, disorganization in the liver lobules extended to all areas. In the first zone of the hepatic acinus, the areas with necrosis and necrobiosis widened. Lympho–plasmocytic infiltrates of various sizes occurred inside the lobules. In the dynamics of the experiment on the 21st – 28th days the morphological structure of the liver differed. Necrotic areas covered large areas of liver tissue with several lobes. Central veins and sinusoids were sharply enlarged. The interlobular connective tissue was swollen, infiltrated by cellular elements of the lympho–plasmocytic row. The liver triads were preserved. Conclusion. The morphogeneses of Paclitaxel–induced and Cisplatin–induced hepatotoxicities have common traits and are characterized by dynamic processes of alteration, compensation and reaction: Days 1–7: growing parenchyma compaction, vacuolar–hydroponic dystrophy of hepatocytes with morphological manifestations of toxic iatrogenic hepatitis; Days 7–14 – the phase of progressive dystrophic changes, which passed into necrobiotic and focal necrotic changes; Days 14–28 – a phase of compensatory changes with some attenuation of inflammatory reactions.
Keywords: liver, chemotherapy medication, Paclitaxel, Cisplatin
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