Bilirubin impairs intestinal regrowth following massive small bowel resection in a rat model.
OBJECTIVE
The purpose of the present study was to evaluate the effects of exogenous bilirubin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS).


METHODS
Male Sprague-Dawley rats were divided into 5 experimental groups: Sham rats underwent bowel transection and reanastomosis, sham multiple doses of bilirubin (MDB) rats underwent bowel transection and were treated with bilirubin, SBS rats underwent a 75% small bowel resection, SBS-SDB (single dose bilirubin) rats underwent a bowel resection and were treated with a single dose of bilirubin, and SBS-MDB underwent a bowel resection and were treated with 3 doses of bilirubin. Bilirubin was administered intraperitoneally from the 7th day through the 14th day postoperatively. Serum total bilirubin concentration over time was evaluated in 5 SBS-SDB rats following a single intraperitoneal dose. Total bilirubin, alanine aminotransferase, and aspartate aminotransferase in serum and parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15.


RESULTS
SBS-SDB and SBS-MDB animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth (vs SBS animals). Bilirubin-treated rats showed a lower apoptotic index in jejunum and ileum and a trend toward an increase in cell proliferation in jejunum and ileum (vs SBS group).


CONCLUSIONS
In a rat model of SBS, exogenous bilirubin inhibits structural intestinal adaptation. Increased cell proliferation and decreased apoptosis may be considered adaptive mechanisms that maintain cell mass.
Sukhotnik
Igor
I
Department of Pediatric Surgery, Bnai Zion Medical Center, 47 Golomb St, PO Box 4940, Haifa 31048, Israel. igor-dr@internet-zahav.net
Shaoul
Ron
R
Lieber
Michael
M
Coran
Arnold G
AG
Abassi
Zaid
Z
Shiloni
Eitan
E
Mogilner
Jorge G
JG
D000714:Anastomosis, Surgical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001663:Bilirubin / Q000097:blood / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects; D006932:Hyperbilirubinemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology
D011506:Proteins; D004247:DNA; D001663:Bilirubin