Antioxidant treatment attenuates hyperglycemia-induced cardiomyocyte death in rats

Fabio Fiordaliso, Roberto Bianchi, Lidia Staszewsky, Ivan Cuccovillo, Mirko Doni, Teresa Laragione, Monica Salio, Costanza Savino, Silvia Melucci, Francesco Santangelo, Eugenio Scanziani, Serge Masson, Pietro Ghezzi, Roberto Latini

Research output: Contribution to journalArticle

Abstract

Diabetes and oxidative stress concur to cardiac myocyte death in various experimental settings. We assessed whether N-acetyl-l-cysteine (NAC), an antioxidant and glutathione precursor, has a protective role in a rat model of streptozotocin (STZ)-induced diabetes and in isolated myocytes exposed to high glucose (HG). Diabetic rats were treated with NAC (0.5 g/kg per day) or vehicle for 3 months. At sacrifice left ventricle (LV) myocyte number and size, collagen deposition and reactive oxygen species (ROS) were measured by quantitative histological methods. Diabetes reduced LV myocyte number by 29% and increased myocyte volume by 20% compared to non-diabetic controls. NAC protected from myocyte loss (+25% vs. untreated diabetics, P <0.05) and reduced reactive hypertrophy (-16% vs. untreated diabetics, P <0.05). Perivascular fibrosis was high in diabetic rats (+88% vs. control, P <0.001) but prevented by NAC. ROS production and fraction of ROS-positive cardiomyocyte nuclei were drastically raised in diabetic rats (2.4- and 5.1-fold vs. control, P <0.001) and normalized by NAC. In separate experiments, isolated adult rat ventricular myocytes were incubated in a medium containing high concentrations of glucose (HG, 25 mM) ± 0.01 mM NAC; myocyte survival (Trypan blue exclusion and apoptosis by TUNEL) and glutathione content were evaluated. The number of dead and apoptotic myocytes increased five and 6.7-fold in HG and glutathione decreased by 48% (P <0.05). NAC normalized cell death and apoptosis and prevented glutathione loss. NAC effectively protects from hyperglycemia-induced myocyte cell death and compensatory hypertrophy through direct scavenging of ROS and replenishment of the intracellular glutathione content.

Original languageEnglish
Pages (from-to)959-968
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume37
Issue number5
DOIs
Publication statusPublished - Nov 2004

Keywords

  • Cell death
  • Diabetes
  • Isolated adult rat ventricular myocytes
  • N-acetylcysteine
  • Oxidative stress
  • Streptozotocin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Fiordaliso, F., Bianchi, R., Staszewsky, L., Cuccovillo, I., Doni, M., Laragione, T., Salio, M., Savino, C., Melucci, S., Santangelo, F., Scanziani, E., Masson, S., Ghezzi, P., & Latini, R. (2004). Antioxidant treatment attenuates hyperglycemia-induced cardiomyocyte death in rats. Journal of Molecular and Cellular Cardiology, 37(5), 959-968. https://doi.org/10.1016/j.yjmcc.2004.07.008