Thesis (Ph.D.)--Chulalongkorn University, 2009

The present study aims to investigate the effects of genistein, a potent phyto-antioxidant, and exercise training on age-induced endothelial dysfunction. Male Wistar rats (20-22-month old) were divided into five groups: 1) aged rats treated with corn oil (Aged+Veh), 2) aged rats treated with genistein (Aged+Gen, (0.25 mg/kg BW/day, s.c.)), 3) aged rats without exercise training (Aged+Without-Ex), 4) aged rats with exercise training (Aged+Ex, swimming 40 min/day, 5 days/week for 8 weeks), and 5) aged rats treated with both genistein and exercise training (Aged+Gen+Ex) group. The cremaster arterioles response to acetylcholine (Ach; 10⁻⁵ M, 5ml/5min) was accessed after 1-min norepinephrine preconstriction (10 μM). To determine NO bioavailability, the Krebs-Ringer buffer with 4, 5-diaminofluorescein-diacetate (3 μM DAF-2DA), and 10 μM Ach saturated with 95%N2 and 5%CO₂ were used. Changes NO-associated fluorescent intensity along the cremaster arterioles were analyzed by the Image Pro-Plus Software. Liver malondialdehyde (MDA) level was measured by thiobarbituric acid reaction and used as an indicator for oxidative stress. TNF-α level was determined by ELISA kit. The results showed that the mean arterial blood pressure (MAP), MDA level and TNF-α level of Aged groups (Aged+Without-Ex and Aged+Veh) were significantly increased when compared to controls. MAP, MDA level and TNF-α level of Aged-treated group (Aged+Gen, Aged+Ex and Aged+Gen+Ex groups) were significantly decreased as compared to their age-matched control groups (P<0.05). In these three groups of treatments, Ach-induced vasodilation after preconstriction with norepinephrine and NO-associated fluorescent intensity were significantly increased as compared to their age-matched control groups (P<0.05). The correlation between, Ach-induced vasodilatation and NO-associated fluorescent intensity was demonstrated and represented by a linear line: y = 0.4276x – 2.0966, R²=0.82, (P<0.01). These findings indicated that genistein and exercise training could improve age-induced endothelial dysfunction via reduced oxidative stress, reduced TNF-α and increased NO bioavailability.