Ferulic acid and not ascorbic acid reversed cardiac energy metabolism disruption in acute aluminum chloride exposed mice via PPARα/AMPK pathway

Objectives Proper cardiac function depends on adequate supply and metabolism of energy substrates. Aluminum chloride exposure has been linked to adverse cardiac events. This study investigated the ameliorative effect of ferulic acid and ascorbic acid in dysregulated cardiac energy metabolism in aluminum chloride-exposed mice. Methods Thirty mice were randomized into five groups (n=6): control (0.1 % distilled water), aluminum chloride (AlCl 3 , 100 mg/kg, p.o ), aluminum chloride and ferulic acid (AlCl 3 , 100 mg/kg; FA 20 , 10 mg/kg, p.o ), aluminum chloride and ferulic acid (AlCl 3 , 100 mg/kg; FA 10 , 10 mg/kg, p.o ), aluminum chloride and ascorbic acid (AlCl 3 , 100 mg/kg; Vit. C, 100 mg/kg), daily for 7 days. Cardiac metabolic enzymes activities were analyzed spectrophotometrically; substrate transporters and regulators of energy metabolism were analyzed using immunohistochemistry. Results AlCl 3 increased hexokinase activity and reduced pyruvate-dehydrogenase activity compared with the control. AlCl 3 significantly reduced the expression of glucose transporter-4 (GLUT 4), carnitine palmitoyl-transferase 1β (CPT1β), peroxisome proliferator-activated receptor-alpha (PPARα) and AMP-activated protein kinase (AMPK) compared with the control. However, FA reversed the effect of AlCl 3 by significantly increasing hexokinase and pyruvate dehydrogenase activities, increasing the expression of GLUT4, CPT1β, PPARα and AMPK. Conclusions FA mitigate against cardiac metabolic disruption caused by acute exposure to AlCl 3 through PPARα and AMPK modulation.