Thesis (Ph.D.)--Chulalongkorn University, 2002

To examine the treatment and preventive effects of genistein on endothelial dysfunction in bilateral ovariectomized rats and also clarify the mechanism(s) of action of genistion on endothelial cells. Female wistar rate were subjected to a bilateral ovariectomy (OVX rat). Sham-operated animals were used as control. These animals were divided into two major groups; treatmdnt and preventive groups. Treatment group was subdivided into five groups. After 3 weeks of washout period, the endothelial dysfunction was confirmed in ovx group (OVX 3-week) comparing with the normally response to vasodilators in the control (Sham 3-week) group. The other animals were further divided into three groups; sham with vehicle (DMSO 100 microlitre/day, sc; Sham veh), ovx with vehicle (DMSO 100 microlitre/day, sc; OVX veh), and ovx with genistein (0.25 mg/kg/day, sc; OVX gen). The preventive group was divided into three subgroups of sham with vehical (Sham veh), ovx with vehicle (OVX veh) and ovx with genistein (OVX gen). The treatment and preventive groups were received genistein or vehicle after washout period and immediately after surgery everyday for 4 and 7 weeks, respectively. Vehicle (DMSO) or genistein were given by the same procedure for both preventive and treatment groups. All parameters were monitored after treatment for 4 weeks and 7 week, respectively. The experimental results of treatment group indicated that mean arterial pressure (MAP) of both OVX 3-week and OVX veh groups were significantly increased as compared to their sham groups (p < 0.05). Interestingly, that significantly increased MAP was not observed in OVX gen. Moreover, the studies of vasodilator responses have demonstrated only for the significant decrement of the response to Ach, not for SNP, in ovx rats. However, the tretment effect of genistein could significantly attenuate this abnormality (p < 0.001). The results of preventive group demonstrated as similar to the treatment group, especially Ach-induced vasorelaxation. It was markedly decreased in OVX veh as compared to Sham veh and OVX gen, respectively (p < 0.001). But the studied for SNP-induced vasorelaxation was unchanged. Moreover, our results demonstratd that INDO (cyclooxygenase inhibitor) could block the effect of genistein on endothelial cells. This result indicated that genistein acted via cyclooxygenase pathway. In conclusion, genistein supplementation might be therapy or prevent endothelial dysfunction mainly via cyclooxygenase pathway. The findings suggested that genistein might be able to used as a new trend for preventing menopausal vascular endothelial dysfunction.