A high isoflavone soy protein diet and intravenous genistein delay rejection of rat cardiac allografts.
Genistein, a soy isoflavone, has in vitro immunosuppressive properties. We investigated whether genistein or dietary soy protein containing isoflavones could influence the outcome of rat cardiac allografts. Lewis rats were fed a diet with protein from high isoflavone soy protein fraction (HIS), casein (CAS) or casein with isoflavones added (CI) starting 1 wk before heart transplants from Wistar Furth donors, and continuing throughout the study. HIS-fed rats had significantly prolonged time to rejection compared with CAS- and CI-fed recipients (10.8 +/- 2.62 vs. 7.18 +/- 0.75 and 7.22 +/- 0.44 d, P < 0.001). Intravenous genistein [20mg/(kg. d) for 14 d] significantly prolonged heart survival compared with controls and dissolvent-treated recipients (23.2 +/- 7.4 vs. 8.4 +/- 1.3 and 11.4+/3.6 d, P < 0.0005), and had an additive effect when given to heart recipients also receiving low dose cyclosporine for 7 d (30.8 +/- 2.3 vs. 23.4 +/- 2.4 d, P < 0.005). Concanavalin A-stimulated lymphocytes, isolated from Lewis rats given intraperitoneal genistein for 7 d, had decreased production of interferon gamma compared with controls or dimethyl sulfoxide-treated groups (22.6 +/- 9.9 vs 149 +/- 105 and 154 +/- 103 micro g/L, P < 0.05). In conclusion, a high isoflavone soy diet and intravenous genistein, but not isoflavone extract alone, delay rejection of rat cardiac allografts, with an additive effect in cyclosporine-treated rats. In addition, intraperitoneal genistein has immunosuppressive properties in vivo.
O'Connor
Timothy P
TP
Department of Surgery, Southern Illinois University School of Medicine, Springfield 62702, USA. toconnor@siumed.edu
Liesen
Daniel A
DA
Mann
Paul C
PC
Rolando
Lori
L
Banz
William J
WJ
D000818:Animals; D004044:Dietary Proteins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019833:Genistein / Q000008:administration & dosage / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D016027:Heart Transplantation / Q000276:immunology*; D007275:Injections, Intravenous; D007529:Isoflavones / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D030262:Soybean Proteins; D014184:Transplantation, Homologous / Q000276:immunology
D004044:Dietary Proteins; D004791:Enzyme Inhibitors; D007529:Isoflavones; D030262:Soybean Proteins; D019833:Genistein