Damaged interlobular bile ducts in primary biliary cirrhosis show reduced expression of glutathione-S-transferase-pi and aberrant expression of 4-hydroxynonenal.
OBJECTIVE
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.
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Japan.
Koichi
K
Tsuneyama
Kenichi
K
Harada
Naoko
N
Kono
Motoko
M
Sasaki
Takahito
T
Saito
M Eric
ME
Gershwin
Mamoru
M
Ikemoto
Hiroyuki
H
Arai
Yasuni
Y
Nakanuma
D000447:Aldehydes / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology* / Q000473:pathology*; D018955:CD36 Antigens / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000502:physiology; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins; D018384:Oxidative Stress / Q000502:physiology; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D000447:Aldehydes; D018955:CD36 Antigens; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D005982:Glutathione Transferase; C027576:4-hydroxy-2-nonenal