Protective Effect of Cholesteryl Hemisuccinate on Fumonisin B1-nduced Apoptosis of Hepatocytes in the Rat Liver.
- Author:
Woo Sung MOON
;
Chul Kyu PARK
;
Myoung Jae KANG
;
Dong Geun LEE
;
Ho Yeul CHOI
- Publication Type:Original Article
- Keywords:
Fumonisin B1;
Cholestery hemisuccinate;
Hepatocyte;
Apoptosis
- MeSH:
Alanine Transaminase;
Animals;
Apoptosis*;
Aspartate Aminotransferases;
Biochemistry;
Cell Death;
Cholesterol;
Hepatocytes*;
Heterochromatin;
In Situ Nick-End Labeling;
Liver*;
Proliferating Cell Nuclear Antigen;
Rats*;
Rats, Sprague-Dawley
- From:The Korean Journal of Hepatology
1999;5(3):227-239
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
