LIVER ULTRASTRUCTURE AFTER ADMINISTRATION OF LORATADINE

Aim. To investigate the influence of a long-time administration of antihistamine drug Loratadine on the ultrastructure of liver. Material and Methods. Experiments were performed on 18 male Wistar rats weighting 160-200 g, which were subdivided into two groups of 9 animals each. The first group of the rats served as a control. Animals of the second group during 30 days were treated with aqueous suspension of Loratadine, which they received through intragastric daily injections in the dose of 0.15 mg / kg body weight. On days 10, 20 and 30 after the last injection (40-th, 50-th and 60-th day of experiment) animals were sacrified and tissue samples of liver were taken for electron microscopic investigation. Results and Discussion. On the 40-th day of the experiment the detected changes involved mainly hepatocytes and were as follows: increased content of pars granulosa in the nucleolus' elevated electron density of the cytoplasm; enhanced amount of lipid inclusions surrounded by the enlarged mitochondria. The latters exposed irregular cristae and impaired inner mitochondrial membrane. Smooth endoplasmic reticulum expressed signs of hyperplasia. On the 50-th day there was noted a decreased ribosomal content in rough endoplasmic reticulum accompanied by lipid infiltration and accumulation of glycogen deposits within the hepatocytes. Inside the liver lobules there were detected local narrowings of Disse space in association with the appearance in these same locations of plasmocytes and fibroblast-like cells. On the 60-th day of experiment the morphology of hepatocytes was similar to that described earlier, although some hepatocytes demonstrated certain signs of intracellular regeneration - i.e. increased content of free polyribosomes and further decondensation of nuclear chromatin. Conclusions. Long lasting application of the highest therapeutic doses of Loratadine induced ultrastructural changes in the liver, which apparently encompass this drug inactivation on the one hand and impairments of hepatocytes on the other. These changes most likely are of transient nature, but may play crucial role in the development of irreversible alterations of liver in association with other hepatotoxic factors (viruses, drugs, psychotropic substances, etc.). Key words: antihistamine drugs, Loratadin, ultrastructure of liver, detoxication