FK778 Does Not Impair Intestinal Allograft Absorption in a Preclinical Model of Total Small Bowel Transplantation

S. Zonta, M. Doni, M. Alessiani, F. Abbiati, M. Bardone, F. Lovisetto, L. Cobianchi, J. Vigano, M. De Martino, D. Kabiri, T. Dominioni, M. Scaglione, A. Bottazzi, P. Poggi, P. Dionigi

Research output: Contribution to journalArticle

Abstract

Malononitrilamide 715 (FK778), a new low-molecular weight immunosuppressant, inhibits both T-cell and B-cell function by acting on the pathway for de novo pyrimidine biosynthesis. Pyrimidines are important for intestinal trophism; their inhibition may predispose to metabolic and functional impairments, such as diarrhea and malabsorption. In this study we assessed the absorptive capacity of intestinal allografts in a large-animal model of small bowel transplantation (SBTx) in pigs chronically treated with FK778. Ten outbred pigs underwent total orthotopic SBTx. Immunosuppression consisted of oral tacrolimus (trough levels 5-15 ng/mL) and oral FK778 (4 mg/kg per day) administered for 60 days. The D-xylose absorption test was performed at day 60 to evaluate carbohydrate absorption. Results were compared to normal controls. Eight of the 10 animals were alive and in good condition at day 60. All of their allografts were free of rejection. The animals had a mean maximal weight loss of 6.4% during the study period; the final weight was comparable to the initial weight (P > .05). Diarrhea was present in all animals (mean 16% of postoperative days). The D-xylose curves showed that absorption in the transplanted animals at day 60 was similar to that in the untreated controls (P > .05). The absence of differences was confirmed by the statistical analysis. In conclusion, our preclinical study in pigs showed that chronic treatment with FK778 in combination with tacrolimus did not impair carbohydrate absorption by the allograft after SBTx.

Original languageEnglish
Pages (from-to)1805-1808
Number of pages4
JournalTransplantation Proceedings
Volume38
Issue number6
DOIs
Publication statusPublished - Jul 2006

Fingerprint

Intestinal Absorption
Allografts
Transplantation
Swine
Xylose
Tacrolimus
Diarrhea
Carbohydrates
Weights and Measures
Pyrimidines
Immunosuppressive Agents
Immunosuppression
Weight Loss
B-Lymphocytes
Animal Models
Molecular Weight
2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide
T-Lymphocytes

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

FK778 Does Not Impair Intestinal Allograft Absorption in a Preclinical Model of Total Small Bowel Transplantation. / Zonta, S.; Doni, M.; Alessiani, M.; Abbiati, F.; Bardone, M.; Lovisetto, F.; Cobianchi, L.; Vigano, J.; De Martino, M.; Kabiri, D.; Dominioni, T.; Scaglione, M.; Bottazzi, A.; Poggi, P.; Dionigi, P.

In: Transplantation Proceedings, Vol. 38, No. 6, 07.2006, p. 1805-1808.

Research output: Contribution to journalArticle

Zonta, S. ; Doni, M. ; Alessiani, M. ; Abbiati, F. ; Bardone, M. ; Lovisetto, F. ; Cobianchi, L. ; Vigano, J. ; De Martino, M. ; Kabiri, D. ; Dominioni, T. ; Scaglione, M. ; Bottazzi, A. ; Poggi, P. ; Dionigi, P. / FK778 Does Not Impair Intestinal Allograft Absorption in a Preclinical Model of Total Small Bowel Transplantation. In: Transplantation Proceedings. 2006 ; Vol. 38, No. 6. pp. 1805-1808.
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AU - Abbiati, F.

AU - Bardone, M.

AU - Lovisetto, F.

AU - Cobianchi, L.

AU - Vigano, J.

AU - De Martino, M.

AU - Kabiri, D.

AU - Dominioni, T.

AU - Scaglione, M.

AU - Bottazzi, A.

AU - Poggi, P.

AU - Dionigi, P.

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AB - Malononitrilamide 715 (FK778), a new low-molecular weight immunosuppressant, inhibits both T-cell and B-cell function by acting on the pathway for de novo pyrimidine biosynthesis. Pyrimidines are important for intestinal trophism; their inhibition may predispose to metabolic and functional impairments, such as diarrhea and malabsorption. In this study we assessed the absorptive capacity of intestinal allografts in a large-animal model of small bowel transplantation (SBTx) in pigs chronically treated with FK778. Ten outbred pigs underwent total orthotopic SBTx. Immunosuppression consisted of oral tacrolimus (trough levels 5-15 ng/mL) and oral FK778 (4 mg/kg per day) administered for 60 days. The D-xylose absorption test was performed at day 60 to evaluate carbohydrate absorption. Results were compared to normal controls. Eight of the 10 animals were alive and in good condition at day 60. All of their allografts were free of rejection. The animals had a mean maximal weight loss of 6.4% during the study period; the final weight was comparable to the initial weight (P > .05). Diarrhea was present in all animals (mean 16% of postoperative days). The D-xylose curves showed that absorption in the transplanted animals at day 60 was similar to that in the untreated controls (P > .05). The absence of differences was confirmed by the statistical analysis. In conclusion, our preclinical study in pigs showed that chronic treatment with FK778 in combination with tacrolimus did not impair carbohydrate absorption by the allograft after SBTx.

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