Intercalated disk damage and cardiac pump function reduction in rats treated with zidovudine and preventive effect of vitamin C

  • Prof Ornella Milanesi, Department of Paediatrics, University of Padova, Italy
  • Prof Anna Belloni, Department of Human Anatomy and Physiology, University of Padua, Italy
  • Dr Lucia Petrelli, Department of Human Anatomy and Physiology, University of Padua
  • Dr Ezia Ruga, Department of Pediatrics, University of Padua, Italy
  • Dr Silvia Ricato, Department of Pediatrics, University of Padua, Italy
  • Dr Muarizio Cavalli, Department of Pharmacology and Anaesthesiology, University of Padua, Italy
  • Prof Gabriella Cargnelli, Department of Pharmacology and Anaesthesiology, University of Padua, Italy
  • Prof Sergio Bova, Department of Pharmacology and Anaesthesiology, University of Padua, Italy

    • Zidovudine (AZT; 3'-azido-3'-deoxythymidine), highly active antiretroviral drug, has been hypothesized to induce myocardial toxicity during long term treatment. This experimental study aims at evaluating by echocardiography, electron microscopy (EM) and immunocytochemistry (ICC) the cardio-toxicity of chronic administration of AZT in rats and the possible preventing effect of vitamin C. Six adult Wistar Kyoto rats received AZT (1 mg/ml) in the drinking water for 8 months, six vitamin C (10 g/kg of food) and AZT, six vitamin C alone, and six served as controls. A 2D-derived m-mode echocardiographic evaluation of the LV Fractional Shortening (FS) was performed at the beginning and before the sacrifice. LV fragments from each rat were processed for EM and light and EM and ICC for visualization of connexin-43, a protein expressed in the in cardiac intercalated discs. Cardiac FS was significantly reduced, compared to untreated animals, by 19.3% (p<0.05) and by 10.1% (p<0.05) in rats treated with AZT and AZT + vitamin C, respectively. However, no statistical difference was detected between these two groups (p> 0.05). Vitamin C by itself did not modify FS (p>0.05). EM showed striking alteration of intercalated discs, totally reverted by the administration of vitamin C. Light microscopy ICC evidenced connexin-43 immunopositivity. EM demonstrated that anti-connexin-43 immunogold was exclusively located in the zones of the intercalated discs. In conclusion, chronic AZT therapy causes a reduction of LV SF and damage of intercalated disk in rats. Concomitant assumption of vitamin C reverse the morphologic damage but restores only partially the functional impairment.