Effect of Bile Acid Replacement on Endotoxin-induced Tumor
Necrosis Factor-a Production in Obstructive Jaundice |
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Authors: | Shyr-Ming Sheen-Chen Han-Shiang Chen Hsin-Tsung Ho Wei-Jen Chen Chih-Chi Sheen Hock-Liew Eng |
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Institution: | (1) 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, TAIWAN;(2) Department of Colon and Rectal Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan, TAIWAN;(3) Department of Pathology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan, TAIWAN;(4) Department of Laboratory Medicine, Mackay Memorial Hospital, 92, Sec. 2, Chungshan North Road, Taipei, Taiwan, TAIWAN |
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Abstract: | There is a high incidence of
perioperative morbidity and mortality in patients with obstructive
jaundice due to sepsis. Tumor necrosis factor-a (TNF-a) is
considered a crucial mediator in inducing and processing the
inflammatory cascade. We hypothesize that obstructive jaundice leads to
an increased endotoxin-induced TNF-a 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-a
levels and biochemical analyses. Comparisons among these three groups
were performed and recorded. While serum and tissue (liver and lung)
TNF-a 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-a production and intestinal bile acid
replacement can inhibit this phenomenon. |
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