Effect of bile acid replacement on endotoxin-induced tumor necrosis factor-alpha production in obstructive jaundice.
There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice due to sepsis. Tumor necrosis factor-a (TNF-alpha) is considered a crucial mediator in inducing and processing the inflammatory cascade. We hypothesize that obstructive jaundice leads to an increased endotoxin-induced TNF-alpha production and that intestinal bile acid replacement can prevent this phenomenon. Sprague-Dawley rats were randomized to three groups of 12 animals each. Group 1 underwent common bile duct ligation (CBDL) with oral intestinal bile acid (deoxycholic acid 5 mg/100 g body weight/3 times daily) replacement (CBDL + bile acid); group 2 underwent common bile duct ligation with the same amount of normal saline replacement orally (CBDL + saline); and group 3 underwent a sham operation (sham control). After 2 days, endotoxin was given to the animals, and after 90 minutes, tissues (liver and lung) and blood were collected for checking the TNF-alpha levels and biochemical analyses. Comparisons among these three groups were performed and recorded. While serum and tissue (liver and lung) TNF-alpha levels of group 2 (CBDL + saline) were significantly increased after endotoxin challenge, these elevations were reduced to control levels (sham control) following oral replacement of intestinal bile acid (CBDL + bile acid). Obstructive jaundice leads to an increased endotoxin-induced TNF-alpha production and intestinal bile acid replacement can inhibit this phenomenon.
Sheen-Chen
Shyr-Ming
SM
Department of Surgery, Division of General Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan.
Chen
Han-Shiang
HS
Ho
Hsin-Tsung
HT
Chen
Wei-Jen
WJ
Sheen
Chih-Chi
CC
Eng
Hock-Liew
HL
D000818:Animals; D001647:Bile Acids and Salts / Q000627:therapeutic use*; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism*; D004731:Endotoxins; D004926:Escherichia coli; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D001647:Bile Acids and Salts; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha