• The Korean Journal of Physiology and Pharmacology
• /
• 제4권2호
• /
• pp.121-127
• /
• 2000

Intracellular accumulation of bile acids in the hepatocytes during cholestasis is thought to be pathogenic in cholestatic liver diseases. The objective of this study was to determine the role of lipid peroxidation and glutathione on the bile acid-induced hepatic cell death mechanism in primary cultured rat hepatocytes. To induce hepatic cell death, we incubated primary cultured rat hepatocytes with glycochenodeoxycholic acid $(GCDC;\;0{\sim}400\;{\mu}M)$ for 3 hours. In electron microscopic examination and agarose gel electrophoresis, low concentration of GCDC treatment mainly induced apoptotic feature. Whereas $400\;{\mu}M$ GCDC treated cells demonstrated both apoptosis and necrosis. Lipid peroxidation was increased dose-dependently in GCDC treated hepatocyte. And this was also accompanied by decreased glutathione. Therefore, oxygen free radical damage may play a partial role in GCDC-induced hepatic cell death.

• 한국자기공명학회논문지
• /
• 제20권2호
• /
• pp.41-45
• /
• 2016

Chemical investigation of a marine-derived fungus, Penicillium sp. 108YD020, resulted in the discovery of six bile acid derivatives, glycocholic acid (1), glycocholic acid methyl ester (2), cholic acid (3), glycochenodeoxycholic acid (4), glycodeoxycholic acid methyl ester (5), and cholic acid methyl ester (6). The structures of six bile acid derivatives 1-6 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권6호
• /
• pp.565-570
• /
• 1999

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 $400\;{\mu}M$ 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.