Effect of Glutamine and Bile Acid on Hepatocyte Apoptosis after Bile Duct Ligation in the Rat

ABSTRACT

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.