Effect of glutamine and bile acid on hepatocyte apoptosis after bile duct ligation in the rat.
Apoptosis is an important process in a wide variety of biologic systems. Cholestasis, or impaired bile formation, occurs in a wide variety of human liver diseases. Retention and accumulation of toxic hydrophobic bile salts in hepatocytes may cause hepatocyte toxicity by inducing apoptosis. In addition, the translocation of bacteria and endotoxin, well documented in patients with obstructive jaundice, contribute to the induction of hepatocyte apoptosis. We hypothesized that oral bile acid replacement, glutamine administration, or both can attenuate or abolish hepatocyte apoptosis. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (10 in each group). Group 1 underwent a sham operation and was simultaneously treated with normal saline. Group 2 underwent common bile duct (CBD) ligation and was simultaneously treated with normal saline. Group 3 underwent CBD ligation and was simultaneously treated with oral glutamine. Group 4 underwent CBD ligation and was simultaneously treated with oral bile acid replacement. After 3 days (n = 5) and 7 days (n = 5), liver tissues were harvested for histopathologic analysis and apoptosis measurements. When compared with the sham operation group, significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation for either 3 or 7 days. After administration of either glutamine or bile acid, the increased hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days were significantly diminished. However, both failed to diminish the changes after CBD ligation for 7 days. Significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation. The administration of either glutamine or bile acid effectively diminished the hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days, whereas both failed to show the same effect after CBD ligation for 7 days.
Sheen-Chen
Shyr-Ming
SM
Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, 123 Ta-Pai Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan. smsheen@yahoo.com
Hung
Kuo-Sheng
KS
Ho
Hsin-Tsung
HT
Chen
Wei-Jen
WJ
Eng
Hock-Liew
HL
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D001651:Cholestasis, Extrahepatic / Q000503:physiopathology*; D003135:Common Bile Duct / Q000601:surgery; D003840:Deoxycholic Acid / Q000502:physiology*; D004195:Disease Models, Animal; D005973:Glutamine / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology*; D008026:Ligation; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D003840:Deoxycholic Acid; D005973:Glutamine