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

Peipei Ping, Christopher P. Baines, Yan Gu, Sumanth D. Prabhu, Jun Zhang, Linda L. Tsai, Ernest Cardwell, Nobel C. Zong, Thomas M. Vondriska, Paavo Korge, Aruni Bhatnagar, Guang Wu Wang

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13 Scopus citations


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.

Original languageEnglish
Pages (from-to)341-351
Number of pages11
JournalCardiovascular Toxicology
Issue number4
StatePublished - 2003


  • Aldehyde-protein adducts
  • Caspase activation
  • Cytochrome c release
  • Myocardial dysfunction
  • Trans-2-hexenal


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