Diisononyl phthalate inhibits cardiac glycolysis and oxidative phosphorylation by down-regulating cytosolic and mitochondrial energy metabolizing enzymes in murine model

Abstract

The recent increase of diisononyl phthalate (DiNP) applications in a wide range of plastic consumer products, as well as its relative environmental exposure and interactions, has compelled an investigation of its toxicity. Phthalate exposure has been associated with heart dysfunction in animals in a few studies, the bulk of which are linked to the high molecular weight phthalates. The effect of DiNP on cardiac energy transduction was assessed utilizing cellular respiration enzymes as indices. Eighteen wistar rats were divided into 3 groups of six rats each: Group A received Tween-80 (control), DiNP (20 mg/kg/BW) was given to Group B, and 200mg/kg DiNP was given to Group C orally (gavage) for 14 days. The activity of cardiac glycolytic, oxidative phosphorylation enzymes and histopathological changes were assessed. The glycolytic and tricarboxylic acid cycle enzymes studied were predominantly down-regulated in a dose-dependent manner, with the exception of cardiac citrate synthase, which showed no significant variation in activity when compared to the control. Furthermore, all respiratory chain complexes (Complex I-IV) decreased significantly relative to control, with the exception of complex IV activity at 20mg/kg/BW which showed no significant difference (P<0.05). Cardiac histopathological alterations confirmed the aforementioned metabolic disturbances. Finally, DiNP exposure impairs cardiac energy transduction enzymes, implying cardiac cells produced insufficient energy (ATP) to carry out its morphological and physiological functions efficiently as the heart requires a constant supply of energy in the form of ATP to support contraction, relaxation, and prevent cardiomyopathies.

Keywords

• Diisononyl phthalate
• Glycolysis
• Mitochondria
• Cardiotoxicity
• Cardiomyopathies
• Mitochondriopathies