Cardiac Toxic Effects of Trans-2-Hexenal are Mediated by Induction of Cardiomyocyte Apoptotic Pathways

Academic Article

Abstract

  • Aldehydes are ubiquitous pollutants with well-indicated but ill-defined cardiovascular toxicity. To investigate the direct toxic effects of environmental aldehyde exposure on the myocardium, 8-wk-old male ICR (Institute of Cancer Research) strain mice were gavage fed trans-2-hexenal (0.1, 1, 10, or 50 mg/kg/wk) of corn oil (vehicle) for 4 wk, during which cardiac function, myocardial morphology, cardiomyocyte apoptosis, and the cytochrome c-mediated caspase activation apoptotic pathway were determined. Quantification by enzyme-linked immunosorbent assay (ELISA) revealed that aldehyde-protein adducts increase in mouse hearts following hexenal treatment, whereas echocardiographic analysis displayed a significant impairment of basal left-ventricular contractile function. Both histological analysis and TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) staining indicated condensed nuclei and a significant increase in cardiomyocyte apoptosis in these mice, but immunohistochemistry-based confocal microscope revealed no marked myofibril disarray. Release of cytochrome c from mitochondria into the cytosol, concomitant with activation of caspase-3 and -9, was also found in hexenal-treated groups. In addition, isolated cardiac mitochondria formed hexenal-protein adducts when treated with hexenal, providing indirect evidence that the cardiac mitochondrion is one of primary subcellular targets of aldehyde toxins. These findings suggest that trans-2-hexenal exposure results in direct cardiac toxicity through, at least in part, induction of mitochondrial cytochrome c release-mediated apoptosis in cardiomyocytes, indicating that the cardiac mitochondrion is one of principal subcellular targets of aldehyde toxins.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Ping P; Baines CP; Gu Y; Prabhu SD; Zhang J; Tsai LL; Cardwell E; Zong NC; Vondriska TM; Korge P
  • Start Page

  • 341
  • End Page

  • 351
  • Volume

  • 3
  • Issue

  • 4