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Piceatannol in combination with low doses of cyclosporine A prolongs kidney allograft survival in a stringent rat transplantation model.

Publication ,  Journal Article
Fernandez, LA; Torrealba, J; Yagci, G; Ishido, N; Tsuchida, M; Tae Kim, H; Dong, Y; Oberley, T; Fechner, J; Colburn, MJ; Schultz, J; Kanmaz, T ...
Published in: Transplantation
December 15, 2002

BACKGROUND: The discovery of new immunosuppressive agents has enhanced short-term graft survival. However, current immunosuppressants often induce toxicities that limit their clinical use. Thus, there is a need for new immunosuppressants for use in clinical transplantation. Piceatannol blocks Syk and ZAP-70, tyrosine kinases involved in immune cell activation. We examined whether piceatannol prolongs kidney allograft survival in the stringent ACI-to-Lewis rat model. METHODS: Kidney recipients were divided into four groups. Group 1 (n=8) received piceatannol 30 mg/kg per day intravenously and cyclosporine A (CsA) 2 mg/kg per day intramuscularly from day -3 to day 7 after transplantation. At day 8, piceatannol was reduced to 10 mg/kg per day and the combined treatment continued until day 60. Group 2 (n=9) received 2 mg/kg per day CsA alone from day -3 to day 60. Group 3 (n=4) received piceatannol alone as in group 1. Group 4 (n=2) received only the vehicle dimethyl sulfoxide from day -3 to day 60. Graft rejection was defined as either a serum creatinine level more than 2 mg/dL or animal death. RESULTS: Group 1 animals survived for at least 115 days (n=8, P<0.05), with several animals maintaining their grafts for more than 200 days. In contrast, 8 of 9 animals in group 2 rejected their grafts within 10 days of transplantation; one animal survived for 71 days. Excellent graft function was maintained in group 1 animals despite withdrawal of immunosuppression. CONCLUSIONS: These results are the first to show that piceatannol, when combined with subtherapeutic dosages of CsA, prevents graft rejection, suggesting that targeting Syk and Zap could be useful for preventing graft rejection.

Duke Scholars

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

December 15, 2002

Volume

74

Issue

11

Start / End Page

1609 / 1617

Location

United States

Related Subject Headings

  • Tyrosine
  • Transplantation, Homologous
  • Thymidine
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • Surgery
  • Stilbenes
  • Stem Cells
  • Reference Values
  • Receptors, Antigen, T-Cell
 

Citation

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Fernandez, L. A., Torrealba, J., Yagci, G., Ishido, N., Tsuchida, M., Tae Kim, H., … Hamawy, M. M. (2002). Piceatannol in combination with low doses of cyclosporine A prolongs kidney allograft survival in a stringent rat transplantation model. Transplantation, 74(11), 1609–1617. https://doi.org/10.1097/00007890-200212150-00020
Fernandez, Luis A., Jose Torrealba, Gökhan Yagci, Nobuhiro Ishido, Masahiro Tsuchida, Hyoung Tae Kim, Yinchen Dong, et al. “Piceatannol in combination with low doses of cyclosporine A prolongs kidney allograft survival in a stringent rat transplantation model.Transplantation 74, no. 11 (December 15, 2002): 1609–17. https://doi.org/10.1097/00007890-200212150-00020.
Fernandez LA, Torrealba J, Yagci G, Ishido N, Tsuchida M, Tae Kim H, et al. Piceatannol in combination with low doses of cyclosporine A prolongs kidney allograft survival in a stringent rat transplantation model. Transplantation. 2002 Dec 15;74(11):1609–17.
Fernandez, Luis A., et al. “Piceatannol in combination with low doses of cyclosporine A prolongs kidney allograft survival in a stringent rat transplantation model.Transplantation, vol. 74, no. 11, Dec. 2002, pp. 1609–17. Pubmed, doi:10.1097/00007890-200212150-00020.
Fernandez LA, Torrealba J, Yagci G, Ishido N, Tsuchida M, Tae Kim H, Dong Y, Oberley T, Fechner J, Colburn MJ, Schultz J, Kanmaz T, Hu H, Knechtle SJ, Hamawy MM. Piceatannol in combination with low doses of cyclosporine A prolongs kidney allograft survival in a stringent rat transplantation model. Transplantation. 2002 Dec 15;74(11):1609–1617.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

December 15, 2002

Volume

74

Issue

11

Start / End Page

1609 / 1617

Location

United States

Related Subject Headings

  • Tyrosine
  • Transplantation, Homologous
  • Thymidine
  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • Surgery
  • Stilbenes
  • Stem Cells
  • Reference Values
  • Receptors, Antigen, T-Cell