Rutin forestalls dysregulated cardiac bioenergetics in bisphenol A and dibutyl phthalate-exposed rats through PPARα and AMPK modulation

Abstract

Proper cardiac function is greatly dependent on adequate supply and metabolism of energy substrates. Environmental pollutants exposure including plasticizers can trigger adverse cardiac metabolic events. This study was designed to investigate the ameliorative effect of rutin (Rt) on dysregulated cardiac energy metabolism in plasticizer-exposed rats. Forty-two rats were randomised into seven groups (n = 6): Control (0.1% dimethyl sulfoxide), bisphenol A (BPA, 25 mg/kg, p.o), dibutyl phthalate (DBP, 25 mg/kg, p.o), BPA + Rt 25 mg/kg, Rt 50 mg/kg, DBP + Rt (25 mg/kg, Rt 50 mg/kg), BPA + DBP and BPA + DBP + Rt, daily for 21 days. BPA and DBP exposure increased plasma glucose, reduced insulin, and increased plasma and cardiac free fatty-acid. Cardiac glucose-6-phosphate level, hexokinase and pyruvate dehydrogenase activities increased in DBP while BPA reduced these variables. Cardiac glucose transporter-4 expression was reduced in BPA group, while cardiac peroxisome proliferator-activated receptor-alpha (PPARα) and AMP-activated protein kinase (AMPK) expression increased in BPA and DBP-treated rats. However, Rt administration prevents impaired cardiac bioenergetics and glucometabolic regulation. Summarily, Rt improves BPA and DBP-impaired cardiac bioenergetics through PPARα and AMPK modulation.