Background/Aims
This study was aimed to examine if FB1 induced-hepatotoxicity involves apoptosis, and cholesteryl hemisuccinate (CS) pre-treatment would selectively interfere with FB1 induced-apoptosis of hepatocytes. Methods: Sprague-Dawley rats were intravenousely injected with FB1 (1.25 mg/kg/day) for two days, and were sacrificed at 3, 6, 12, 24 and 48 hours after injection. Another experiment group was composed of rats with pretreatment of CS (100 mg/kg/day, i.p.) before FB1 injection. Results: This study demonstrated that administration of hepatotoxic dose of FB1 to Sprague-Dawley rats resulted in liver injury leading to cell death by apoptosis. FB1-induced apoptosis was preceded by early elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, and appearance of injured pre-apoptotic cells at 12 hours was followed by massive fragmentation and margination of heterochromatin at 24 hours. CS pre-treatment prior to FB1 injection ameliorated serum biochemistry and hepatic injury with apoptosis, demonstrated by histological, ultrastructural and TUNEL (terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling) methods. In addition, there was remarkable decrease in number of PCNA (proliferative cell nuclear antigen)-positive proliferating hepatocytes compared to that of FB1 treated group. Conclusion: This study suggests that apoptosis significantly contributes to FB1-induced hepatotoxicity in vivo, and pre-exposure of rat to CS prevents FB1-induced hepatic apoptosis and proliferation. (Korean J Hepatol 1999;5:227－239)
