Glycochenodeoxycholic acid induces cell death in primary cultured rat hepatocyte: Apoptosis and necrosis.
- Author:
Sang Hui CHU
1
;
Wol Mi PARK
;
Kyung Eun LEE
;
Young Sook PAE
Author Information
1. Department of Pharmacology, College of Medicine, Ewha Womans University, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Hepatocyte;
GCDC;
Apoptosis;
Necrosis
- MeSH:
Animals;
Apoptosis*;
Bile;
Bile Acids and Salts;
Cell Death*;
Cell Survival;
Cholestasis;
Chromatin;
Cytoplasm;
Glycochenodeoxycholic Acid*;
Hepatocytes*;
In Situ Nick-End Labeling;
L-Lactate Dehydrogenase;
Liver;
Liver Diseases;
Membranes;
Necrosis*;
Propidium;
Rats*
- From:The Korean Journal of Physiology and Pharmacology
1999;3(6):565-570
- CountryRepublic of Korea
- Language:English
-
Abstract:
Intracellular accumulation of bile acids in the hepatocytes during cholestasis is thought to be pathogenic in cholestatic liver injury. Due to the detergent-like effect of the hydrophobic bile acids, hepatocellular injury has been attributed to direct membrane damage. However histological findings of cholestatic liver diseases suggest apoptosis can be a mechanism of cell death during cholestatic liver diseases instead of necrosis. To determine the pattern of hepatocellular toxicity induced by bile acid, we incubated primary cultured rat hepatocytes with a hydrophobic bile acid, Glycochenodeoxycholate (GCDC), up to 5 hours. After 5 hours incubation with 400 muM GCDC, lactate dehydrogenase released significantly. Cell viability, quantitated in propidium iodide stained cells concomitant with fluoresceindiacetate was decreased time-and dose-dependently. Most nuclei with condensed chromatin and shrunk cytoplasm were heavily labelled time- and dose-dependently by a positive TUNEL reaction. These findings suggest that both apoptosis and necrosis are involved in hepatocytes injury caused by GCDC.
