Introduction: Alterations in cardiac energy metabolic pathways arising from exposure to environmental pollutants have been linked to the development of cardiac dysfunction. Crotonaldehyde (CRO), a hazardous environmental pollutant, has been reported to be cardio-toxic.

 

Aim: However, dearth of information exists on the effect of CRO exposure on cardiac energy metabolism with respect to its cardio-toxicity. This study was therefore designed to investigate cardiac energy metabolism in male Wistar rats exposed to CRO.

 

Method: 36 male Wistar rats (150-170g; n=9) were grouped into 4 (I-IV): Control (10mL/kg normal-saline), CRO (0.75, 1.5, and 2.5mg/kg, p.o) for 28 days. Blood samples were obtained and evaluated for plasma Creatinine Kinase-Myocardial band (CK-Mb), cardiac troponin-I (cTnI), glucose, triglyceride, Free Fatty Acid (FFA) and insulin levels by spectrophotometry. Cardiac triglyceride, FFA, pyruvate, glucose-6-phosphate, cardiac hexokinase, pyruvate dehydrogenase (PDH) and nuclear factor erythroid-2 related-factor (Nrf2) activities were determined using ELISA. Cardiac malondialdehyde (MDA), hydrogen peroxide (H₂O₂), reduced glutathione (GSH) level, superoxide dismutase (SOD), and catalase activities were measured by spectrophotometry. Cardiac glucose transporter-4 (GLUT4), Peroxisome Proliferator-activated Receptor-alpha (PPARα), Carnitine Palmitoyl Transferase-1β (CPT1β) and AMP-activated Protein Kinase (AMPK) activities were determined immunohistochemically. Data were analysed using descriptive statistics and ANOVA at α_0.05. This study complied with ethical standard and was approved by the University of Ibadan Animal Care and Use Research Ethics Committee (UI-ACUREC/18/007).

 

Results: Levels of CK-Mb, cTnI, glucose increased significantly while plasma and cardiac triglyceride, FFA, and insulin reduced significantly in all CRO-treated groups compared with control. Cardiac Pyruvate level, hexokinase and PDH activities increased significantly in all CRO-treated groups compared with control. Cardiac levels of MDA and H₂O₂ increased significantly while GSH and Nrf2 reduced; SOD and CAT activities decreased following CRO exposure compared with control. Cardiac GLUT4 (15.31 and 28.86 %) and PPARα (73.25, 102.79 %) expression increased in groups II and III, while CPT1β expression decreased in group II (66.46 %) but increased in groups III and IV (52.80 and 33.45 %) compared with control.

 

Conclusion: Crotonaldehyde exposure exerts cardio-toxic effects by altering cardiac energy metabolism resulting in reduced free fatty acid, increased glucose uptake and utilization; down-regulation of nuclear factor erythroid-2 related-factor and up-regulation of peroxisome proliferator-activated receptor-alpha.

 

Keywords:      Crotonaldehyde, energy metabolism, cardio-toxicity, redox imbalance