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01.06.2010

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

verfasst von: Ravi Kumar Arvapalli, Satyanarayana Paturi, Joseph P. Laurino, Anjaiah Katta, Sunil K. Kakarla, Murali K. Gadde, Miaozong Wu, Kevin M. Rice, Ernest M. Walker, Paulette Wehner, Eric R. Blough

Erschienen in: Cardiovascular Toxicology | Ausgabe 2/2010

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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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Titel: Deferasirox Decreases Age-Associated Iron Accumulation in the Aging F344XBN Rat Heart and Liver
verfasst von: Ravi Kumar Arvapalli
Satyanarayana Paturi
Joseph P. Laurino
Anjaiah Katta
Sunil K. Kakarla
Murali K. Gadde
Miaozong Wu
Kevin M. Rice
Ernest M. Walker
Paulette Wehner
Eric R. Blough
Publikationsdatum: 01.06.2010
Verlag: Humana Press Inc
Erschienen in: Cardiovascular Toxicology / Ausgabe 2/2010
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-010-9068-9

Springer Medizin

Abstract

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