title: Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome.
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 (n=20) and WKY (n=20) animals were ovariectomized (OVX). Four weeks after surgery all animals were randomized to receive either genistein (54 mg/human equivalent dose/day for 4 weeks), 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- and sodium nitroprusside-induced relaxation of aortic rings as well as NG-L-arginine (L-NMA: 10-100 mM) induced vasoconstriction in phenylephrine-precontracted aortic segments. Liver expression of the peroxisome proliferator-activated receptor alpha (PPARA and gamma (PPARG 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 mM, 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 PPARA and PPARG. Our data suggest that genistein is effective in ameliorating cardiovascular profiles in an experimental model of postmenopausal metabolic syndrome, attenuating the features of this disease. The effects of genistein are likely mediated by PPARA and PPARG receptors. This evidence would support the rationale for some pilot clinical trials using genistein in postmenopausal women affected by metabolic syndrome.
authors.affiliation: Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, c/o AOU Policlinico G. Martino, Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Antonio
authors.initials: A
authors.lastname: Bonaiuto
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Stefano
authors.forename: Daniela
authors.initials: D
authors.lastname: Giuliani
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guarini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arcoraci
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D004435:Eating; D005260:Female; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D009765:Obesity; D010052:Ovariectomy; D017698:Postmenopause / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D019833:Genistein