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Deferasirox Decreases Age-Associated Iron Accumulation in the Aging F344XBN Rat Heart and Liver

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Abstract

It is thought that aging in rats and humans is associated with increases in iron accumulation and cell apoptosis. Here, we examine the relationship between cardiac iron levels and apoptosis in aged F344XBN rats that had been treated with an oral iron chelator (Deferasirox; 100 mg/kg body weight) on alternate days for 6 months. Compared to adult animals (6 month), cardiac iron (+72%), liver iron (+87%), ferritin light chain (+59%), divalent metal transporter-1 (+56%) and the number of TdT-mediated dUTP nick end labeling (TUNEL) positive cells (4.3 fold increase) were higher in 33-month-old animals (P < 0.05). Deferasirox treatment decreased cardiac iron levels by 37% (P < 0.05), and this was associated with decreases in the number of TUNEL-positive cells. Age-associated increases in cell death were coupled with increases in Bax to Bcl-2 ratio, and the amount of Bad, full-length caspase-3, and cleaved caspase-3. Deferasirox treatment decreased the Bax to Bcl-2 ratio by 17% (P < 0.05) and the amount of Bad, full-length caspase-3, cleaved caspase-3 (19 kDa), and cleaved caspase-3 (17 kDa) by 41, 16, 22, and 37%, respectively (P < 0.05). Taken together, these data suggest that deferasirox may be effective in diminishing age-associated iron accumulation and cardiac apoptosis in the F344XBN rat model.

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Acknowledgments

This study was supported by funding from Novartis Pharmaceutical to E. R. B.

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Authors and Affiliations

  1. Department of Biological Sciences, Marshall University, Huntington, WV, USA

    Ravi Kumar Arvapalli, Satyanarayana Paturi, Murali K. Gadde, Miaozong Wu, Kevin M. Rice & Eric R. Blough

  2. Cell Differentiation and Development Center, Marshall University, Huntington, WV, USA

    Ravi Kumar Arvapalli, Satyanarayana Paturi, Murali K. Gadde, Miaozong Wu, Kevin M. Rice, Ernest M. Walker & Eric R. Blough

  3. Department of Chemistry, University of Tampa, Tampa, FL, USA

    Joseph P. Laurino

  4. Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    Anjaiah Katta, Sunil K. Kakarla, Ernest M. Walker & Eric R. Blough

  5. Department of Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    Paulette Wehner

  6. Department of Exercise Science, Sport and Recreation, College of Education and Human Services, Marshall University, Huntington, WV, USA

    Eric R. Blough

  7. Laboratory of Molecular Physiology, #241N Byrd Biotechnology Building, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755-1090, USA

    Eric R. Blough

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  1. Ravi Kumar Arvapalli
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Correspondence to Eric R. Blough.

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Arvapalli, R.K., Paturi, S., Laurino, J.P. et al. Deferasirox Decreases Age-Associated Iron Accumulation in the Aging F344XBN Rat Heart and Liver. Cardiovasc Toxicol 10, 108–116 (2010). https://doi.org/10.1007/s12012-010-9068-9

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