Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal.

Abstract

BACKGROUND/AIMS:

Chronic inflammation induces oxidative stress by producing reactive oxygen species. We investigated how the oxidative stress associated with chronic cholangitis induce bile duct damages in primary biliary cirrhosis.

METHODS:

The intracellular status of lipid peroxidation due to oxidative stress and that of glutathione, an endogenous cytoprotective molecule, were examined in primary biliary cirrhosis and controls by immunostaining of 4-hydroxynonenal and glutathione-S-transferase-pi. The former is a by-product of lipid peroxidation, and the latter is involved in the formation of intracellular glutathione.

RESULTS:

In the damaged bile ducts of primary biliary cirrhosis, glutathione-S-transferase-pi expression was markedly reduced, reflecting reduction of intracellular glutathione, and perinuclear expression of 4-hydroxynonenal was frequent, reflecting active lipid peroxidation associated with biliary epithelial damages. There was diffuse/luminal expression of 4-hydroxynonenal in the bile ducts frequent in primary biliary cirrhosis and controls, likely reflecting absorption of 4-hydroxynonenal, also a component of oxidized low-density lipoprotein, from bile via scavenger receptor class B type 1 on biliary epithelium.

CONCLUSIONS:

The data suggest that lipid peroxidation in the bile ducts with reduced expression of glutathione-S-transferase-pi, may be an important pathologic process leading to the bile duct damage of primary biliary cirrhosis.

• Authors: Koichi Tsuneyama, Kenichi Harada, Naoko Kono, Motoko Sasaki, Takahito Saito, M Eric Gershwin, Mamoru Ikemoto, Hiroyuki Arai, Yasuni Nakanuma
• Journal: Journal of hepatology (J Hepatol) Vol. 37 Issue 2 Pg. 176-83 (Aug 2002) ISSN: 0168-8278 [Print] Netherlands
• PMID: 12127421 (Publication Type: Journal Article)

Chemical References

• Aldehydes
• CD36 Antigens
• Membrane Proteins
• Receptors, Immunologic
• Receptors, Lipoprotein
• Receptors, Scavenger
• SCARB1 protein, human
• Scarb1 protein, mouse
• Scavenger Receptors, Class B
• Glutathione Transferase
• 4-hydroxy-2-nonenal

Topics

• Aldehydes (metabolism)
• Bile Ducts, Intrahepatic (enzymology, pathology)
• CD36 Antigens (metabolism)
• Female
• Glutathione Transferase (metabolism)
• Humans
• Immunohistochemistry
• Lipid Peroxidation (physiology)
• Liver Cirrhosis, Biliary (metabolism, pathology)
• Male
• Membrane Proteins
• Oxidative Stress (physiology)
• Receptors, Immunologic
• Receptors, Lipoprotein
• Receptors, Scavenger
• Scavenger Receptors, Class B