Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidation and improves flow-mediated vasodilatation in obese subjects
R. Garg et al., Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidation and improves flow-mediated vasodilatation in obese subjects, HYPERTENSIO, 36(3), 2000, pp. 430-435
Citations number
24
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Because troglitazone has been shown to have antioxidant properties, we inve
stigated whether troglitazone administration to obese subjects causes a red
uction in (1) reactive oxygen species (ROS) generation by polymorphonuclear
leukocytes (PMNLs) and mononuclear cells (MNCs) and (2) lipid peroxidation
as reflected in the plasma concentrations of 9-hydroxyoctadecadienoic acid
(9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE). Seven obese subject
s were given 400 mg/d troglitazone for 4 weeks. Blood samples were obtained
before troglitazone administration and at weekly intervals thereafter. Ins
ulin concentrations fell significantly at week 1 and remained low at weeks
2 and 4 (P<0.001). ROS generation by PMNLs fell to 77.6+/-25.1% of the basa
l at week 1 and 47.9+/-41.1% at week 4 (P<0.001). ROS generation by MNCs fe
ll to 59.8+/-15.7% of the basal at week 1 and 35.1+/-17.6% at week 4 (P<0.0
01). 9-HODE and 13-HODE concentrations fell significantly from 787.4+/-52.4
and 713.1+/-44.7 pg/mL to 720.4+/-66.7 (P<0.004) and 675.2+/-65.0 pg/mL (P
<0.01) after 4 weeks, respectively. Postischemic dilatation of the brachial
artery was measured by ultrasonography. The mean percent dilatation after
forearm ischemia before and after troglitazone was 5.5+/-3.01% and 8.75+/-3
.37% (P<0.02), respectively. The percent increase in diameter after nitrogl
ycerin was 17.08+/-1.18% before troglitazone, whereas it was 18.9+/-1.91% (
P<0.02) after troglitazone. We conclude that troglitazone has a potent and
rapid biological inhibitory effect on ROS generation by PMNLs and MNCs and
that it inhibits lipid peroxidation significantly. These changes are associ
ated with a significant improvement in postischemic flow-mediated vasodilat
ion in the brachial artery over a relatively short period of 4 weeks.