Glutamine reduces bacterial translocation after small bowel transplantation in cyclosporine-treated rats.
Bacterial translocation (BT) of enteric organisms is a major cause of sepsis in patients undergoing small bowel transplantation (SBT). Cyclosporine (CsA) may be toxic to intestinal epithelium and increase the risk of BT. Glutamine (Gln) is the preferred enterocyte fuel and maintains graft epithelial integrity in experimental SBT. This study determined the effects of CsA on mucosal structure and function of transplanted intestinal isograft and examined whether Gln-enriched diet reversed CsA-induced intestinal toxicity. Thirty-three adult Lewis rats underwent resection of the distal 60% of small bowel and received an orthotopic jejunal isograft. Rats received either elemental diet with 2% Gln or the same diet with balanced nonessential amino acids (non-Gln) by gastrostomy for 10 days. CsA (15 mg/kg, im) or olive oil was injected daily. Rats were assigned to four groups: non-Gln with vehicle, non-Gln with CsA, Gln with vehicle, and Gln with CsA. Mucosal villous height, surface area, crypt depth, 14C glucose absorption, BT to mesenteric lymph nodes (MLN), and body weight change were evaluated. The non-Gln with CsA group had the highest incidence of BT (P < 0.001). Gln groups had significantly decreased BT (P < 0.01) and increased crypt depth and villous surface area (P < 0.01) when compared to non-Gln groups. Body weight significantly decreased in CsA groups when compared to non-CsA groups (P < 0.01). These results indicate at CsA significantly decreased body weight and increased BT without decreasing mucosal structure and glucose absorption of intestinal isografts.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
W
W
Department of Surgery, University of Pennsylvania, Philadelphia 19104.
Frankel
W L
WL
Bain
A
A
Choi
D
D
Klurfeld
D M
DM
Rombeau
J L
JL
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D016572:Cyclosporine / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000382:microbiology / Q000473:pathology / Q000637:transplantation*; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D009068:Movement; D010289:Parenteral Nutrition, Total; D051381:Rats; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic; D015431:Weight Loss / Q000187:drug effects
D005973:Glutamine; D016572:Cyclosporine; D005947:Glucose