THE ROLE OF THYROXINE HORMONE ADMINISTRATION ONACETAMINOPHEN-INDUCED HEPATIC INJURY:HISTOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY
Lamiaa I. Abdel Fattah, Mohamed H. Ahmed and Tarek A. El-Ghamrawy*
Departments of Histology and *Anatomy, Faculty of Medicine, Cairo University
Acetaminophen (ACAP) is a widely used analgesic and a known hepatotoxic agent. The present study aimed at investigating the possible stimulating effect of administration of thyroxine hormone on liver regeneration after acetaminophen induced liver insult. Twenty-five male adult albino rats were divided into three groups: ?, ??, and ???: Control, ACAP-treated and ACAP with thyroxine-treated groups respectively. The animals of group II and III received single ACAP injection, followed by one week thyroxine hormone injection for group III only. Animals were sacrificed and the liver sections were stained with H&E, and immunohistochemically using Cyclin D1, proliferating cell nuclear antigen (PCNA), as well as vascular endothelial growth factor (VEGF). The percentage of nuclear Cyclin D1 and nuclear PCNA immunoexpression and the optical density of nuclear Cyclin D1 and nuclear PCNA were assessed, in addition to the area percent of VEGF. Statistical analysis was performed. In ACAP-treated group (group II) the centrilobular area revealed multiple vacuolated hepatocytes, congestion of the central veins and blood sinusoids and exudation of eosinophilic material. ACAP and thyroxine-treated group (group III) showed few vacuolated hepatocytes in the centrilobular and midzonal areas of the liver lobule with congestion of central veins and blood sinusoids. The nuclei of some hepatocytes revealed faint positive PCNA immunoreaction in ACAP-treated group. More intense PCNA immunoreaction and increased PCNA immunoexpression were seen in ACAP and thyroxine-treated group. In the latter group a significant increase in the mean percentage of PCNA positive nuclei and the mean optical density of immunoreaction were detected. Cyclin D1 immunoexpression showed weak nuclear reaction in some hepatocytes of ACAP-treated group and an increased number of immune positive nuclei and the optical density of this reaction in ACAP and thyroxine-treated group. The area percent of VEGF immunoexpression increased markedly in ACAP and thyroxine-treated group than in ACAP-treated one. It could be concluded that thyroxine induced hepatocyte proliferation through increased cyclin D1 protein in their nuclei. It also restored the hepatic sinusoids through endothelial proliferation detected by VEGF.