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 (Cl) 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 Cl-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 dj 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 γ compared with controls or dimethyl sulfoxide-treated groups (22.6 ± 9.9 vs 149 ± 105 and 154 ± 103 μg/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.