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KMID : 0811719990030060565
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Korean Journal of Physiology & Pharmacology
1999 Volume.3 No. 6 p.565 ~ p.570
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Glycochenodeoxycholic Acid Induces Cell Death in Primary Cultured Rat Hepatocyte: Apoptosis and Necrosis
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Sang Hui Chu
Wol Mi Park/Kyung Eun Lee/Young Sook Pae
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Abstract
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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 400μM 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.
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KEYWORD
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Hepatocyte, GCDC, Apoptosis, Necrosis,
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