Vitis vinifera (grape) seed extract and resveratrol alleviate bisphenol-A-induced metabolic syndrome: Biochemical and molecular evidences.

ABSTRACT

The mechanisms of bisphenol-A (BPA)-induced metabolic syndrome as well as the protective role of grape seed extract (GSE) and resveratrol were investigated. Rats were treated with BPA (0 and 35 mg·kg-1 ·day-1 , gavage) plus resveratrol (25, 50, and 100 mg·kg-1 ·day-1 , i.p.) or GSE (3, 6, 12 mg·kg-1 ·day-1 , i.p.) or vitamin E (200 IU/kg/every other day, i.p.). After 2 months, mean systolic blood pressure, serum lipid profile, glycaemia, and fat index were examined. By enzyme-linked immunosorbent assay, the serum concentrations of insulin, leptin, adiponectin, and paraoxonase 1, and by real-time polymerase chain reaction as well as western blotting, key liver elements in cholesterol hemostasis (LDLR, CYP7A1, ABCG5 and 8) and insulin signaling (p-Akt/Akt and p-PI3K/PI3K) were measured. BPA increased mean systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol and reduced paraoxonase1 and the hepatic expression of both ABCG5 and ABCG8. It increased the body fat index, leptin, adiponectin, insulin, and glycaemia level and decreased the hepatic protein expression of p-Akt/Akt and p-PI3K/PI3k. GSE, resveratrol, or vitamin E coadministration along with BPA restored the detrimental effects of BPA in some levels. Herein, the predisposing effects of BPA-induced metabolic syndrome were restored by GSE and resveratrol, linked to the regulation of insulin signaling, ABCG8 expression, and their antioxidant properties.