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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0206v1 200/3/367    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bitto, A. Articles by Squadrito, F. Search for Related Content PubMed PubMed Citation Articles by Bitto, A. Articles by Squadrito, F.

A Bitto, messina, Italy
D Altavilla, Messina, Italy
F Polito, Messina, Italy
A Bonaiuto, Messina, Italy
L Minutoli, Messina, Italy
V Di Stefano, Messina, Italy
D Giuliani, Messina, Italy
S Guarini, Messina, Italy
V Arcoraci, Messina, Italy
F Squadrito, Dep of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, 98123, Italy

Correspondence: Francesco Squadrito, Email: francesco.squadrito{at}unime.it

Abstract

Genistein aglycone, a soy derived isoflavone, has been demonstrated to be effective in reducing cardiovascular risk in postmenopausal women. We therefore investigated its effects in an experimental model of postmenopausal metabolic syndrome. Female spontaneously hypertensive obese rats (SHROB, n=40), a genetic model of syndrome X, and age-matched Wistar Kyoto (WKY, n=40) rats were used. A group of SHROB and WKY were ovariectomized (OVX). Four weeks after surgery all animals were randomized to receive either genistein (54mg/human equivalent dose/day for 4wks), or vehicle. Body weight, food intake, systolic blood pressure (SBP), heart rate, plasma glucose, insulin resistance (HOMA-IR), total plasma cholesterol and triglycerides, and uterine weights were studied. Furthermore, we investigated acetylcholine (Ach)- and sodium nitroprusside (SN)-induced relaxation of aortic rings as well as NG-L-arginine induced vasoconstriction in phenylephrine precontracted aortic segments. Liver expression of the peroxisome proliferator-activated receptor alpha and gamma was also assessed.

OVX animals had a slight increase in SBP, body weight, insulin resistance and plasma cholesterol. OVX-SHROB rats showed also impaired endothelial responses, blunted L-NMA induced contraction (L-NMA 100 microM: WKY = 2.2±0.3 g/mg tissue; OVX -SHROB = 1.1±0.4 g/mg tissue). Genistein treatment decreased SBP and plasma lipids, ameliorated endothelial dysfunction and insulin resistance, increased HDL-cholesterol and enhanced liver expression of PPAR- and PPAR-.

Our data suggest that genistein is effective in ameliorating cardiovascular profile in an experimental post-menopausal metabolic syndrome, attenuating the features of this disease. The effects of genistein are likely mediated by PPARs. These evidences would support the rationale for using genistein in post-menopausal women affected by metabolic syndrome.