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

Authors
LUIS A. FERNANDEZJOSE TORREALBAG¨OKHAN YAGCINOBUHIRO ISHIDOMASAHIRO TSUCHIDAHYOUNG TAE KIMYINCHEN DONGTERRY OBERLEYJOHN FECHNERMATTHEW J. COLBURNJACKIE SCHULTZTURAN KANMAZHUAIZHONG HUSTUART J. KNECHTLEMAJED M. HAMAWY
Department
Dept. of Surgery (외과학)
Issue Date
2002
Citation
Transplantation, Vol.74(11) : 1609-1617, 2002
ISSN
0041-1337
Abstract
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.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34709
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
Keimyung Author(s)
김형태
Full Text
https://insights.ovid.com/pubmed?pmid=12490796
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