Dietary medium-chain triglycerides prevent chemically induced experimental colitis in rats.
The effects of dietary medium-chain triglycerides (MCTs) on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) were investigated in rats. Male Wistar rats were given an intracolonic injection of TNBS and were then fed liquid diets containing MCTs or corn oil (AIN93) as controls. Serum and tissue samples were collected 1 week after TNBS enema. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase (MPO) activity was measured. Furthermore, messenger RNA (mRNA) and protein levels for inflammatory cytokines and a chemokine were assessed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In another set of experiments, the protein expression of Toll-like receptor (TLR)-4 in the colon was measured 1 week after feeding of liquid diets. To investigate the effects of MCTs on macrophages, RAW246.7 macrophages were incubated with media containing albumin conjugated with MCT or linoleic acid, which is the major component of corn oil. Then, the production of tumor necrosis factor-alpha (TNF-alpha) was measured. Dietary MCTs blunted significantly the protein levels of TLR-4 in the colon. Furthermore, the expression of TLR-4 was significantly blunted in RAW264.7 cells incubated with MCTs compared with cells incubated with linoleic acid. Induction of interleukin 1beta (IL-1beta), TNF-alpha, and macrophage inflammatory protein-2 (MIP-2) in the colon was attenuated by dietary MCT. Furthermore, MPO activities in the colonic tissue were significantly blunted in animals fed the MCT diets compared with those fed the control diets. As a result, dietary MCTs improved chemically induced colitis significantly. MCTs most likely are useful for the therapy of inflammatory bowel disease as an anti-inflammatory immunomodulating nutrient.
Kono
Hiroshi
H
First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan. hkouno@yamanashi.ac.jp
Fujii
Hideki
H
Ishii
Kenichi
K
Hosomura
Naohiro
N
Ogiku
Masahito
M
D000818:Animals; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000032:analysis; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D003106:Colon / Q000201:enzymology / Q000473:pathology; D004731:Endotoxins / Q000097:blood; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000235:genetics; D014280:Triglycerides / Q000008:administration & dosage*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D054426:Chemokine CXCL2; D004731:Endotoxins; D053583:Interleukin-1beta; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase