title: Influence of long-term, high-dose dexamethasone administration on proliferation and apoptosis in porcine hepatocytes.
abstract: The aim of this study was to examine the influence of long-term, high-dose dexamethasone administration on the liver, with particular emphasis on hepatocyte proliferation and apoptosis, using a swine model. The study included 48 large, female Polish breed pigs aged 3months (weighing ca. 30kg) divided into groups I (control; n=24) and II (dexamethasone; n=24) that receiving intra-muscular injections of monosodium phosphate dexamethasone for 29days. The pigs were euthanized on days subsequent to the experiment. Immediately after the euthanasia, the pig livers were sampled, fixed, and processed routinely for histopathology, histochemistry, and immunohistochemistry (for proliferating cell nuclear antigen, Bcl-2, and caspase-3). Apoptosis was visualized by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL). Dexamethasone administration gradually caused hepatocyte glycogen degeneration and finally lipid degeneration, accompanied by sinusoid and central vein dilatation and nuclear chromatin condensation. The proliferating cell nuclear antigen index, mean number of argyrophilic nucleolar organizer regions and proliferation index of argyrophilic nucleolar organizer regions were lower, while Bcl-2 expression was higher in group II compared with group I. The results from this study suggest that safe high-dose dexamethasone administration time is difficult to establish. Long-term, high-dose dexamethasone administration can cause pronounced morphological changes in hepatocytes by diminishing their transcriptional and proliferation activity but also protects them from apoptosis by potentially affecting Bcl-2 expression.
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland. Electronic address: mateusz.mikiewicz@uwm.edu.pl.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Mikiewicz
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Otrocka-Domagała
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Paździor-Czapula
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Rotkiewicz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D022781:Hepatocytes / Q000187:drug effects*; D013552:Swine
chemical_list: D003907:Dexamethasone; D053148:Caspase 3
keywords: Apoptosis; Dexamethasone; Glucocorticosteroids; Liver; Proliferation; Swine