Catechin prevents endothelial dysfunction in the prediabetic stage of OLETF rats by reducing vascular NADPH oxidase activity and expression.
OBJECTIVE
In the prediabetic stage, hyperinsulinemia or insulin resistance is thought to be closely associated with oxidative stress, which is also the main contributor of endothelial dysfunction. Clinical studies have indicated that regular intake of green tea reduces the risk of cardiovascular diseases. This study examined whether catechin prevents endothelial dysfunction and hyperglycemia in the prediabetic stage of a type 2 diabetic (T2D) rat, the Otsuka Long-Evans Tokushima Fatty (OLETF) model.


RESULTS
30 OLETF rats, 13 week-old, were randomized into two equal groups for daily treatment with either catechin (30 mg/kg/day), Catechin-OLETF) or saline for 12 weeks. Intraperitoneal glucose tolerance tests and blood pressure measurements were performed at 13 and 25 weeks. Ex vivo vascular relaxation was assessed in organ chambers, vascular superoxide anion production by dihydroethidine, vascular NADPH oxidase activity by lucigenin, and expression by immunohistochemistry. Catechin significantly reduced blood pressure (OLETF vs. Catechin-OLETF; 138+/-16 mmHg vs. 126+/-16 mmHg, p=0.013), fasting sugar (129+/-11 mg/dL vs. 118+/-9 mg/dL, p=0.02) and the insulin level (2.13+/-1.29 ng/mL vs. 0.53+/-0.27 ng/mL, p=0.004). In the aorta of Catechin-OLETF at 25 weeks, endothelium-dependent relaxations were significantly improved and NADPH oxidase activity in aortic rings was markedly decreased compared with those of OLETF. Catechin reduced vascular reactive oxygen species formation in the aorta and suppressed the expression of p22phox and p47phox NADPH oxidase subunits.


CONCLUSIONS
Intake of catechin normalized blood pressure and prevented endothelial dysfunction and insulin resistance in the prediabetic stage. Prevention of vascular oxidative stress by inhibiting NADPH oxidase expression and activity is likely to contribute to the beneficial effect on the vascular system.
Ihm
Sang-Hyun
SH
Cardiovascular Center, Seoul St. Mary's Hospital, the Catholic University of Korea, 505 Banpo-dong, Seoul, Republic of Korea.
Lee
Jung-Ok
JO
Kim
Su-Jin
SJ
Seung
Ki-Bae
KB
Schini-Kerth
Valérie B
VB
Chang
Kyuk
K
Oak
Min-Ho
MH
D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011236:Prediabetic State / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D020334:Rats, Inbred OLETF
D001786:Blood Glucose; D007328:Insulin; D002392:Catechin; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1