Deferasirox Decreases Age-Associated Iron Accumulation in the Aging F344XBN Rat Heart and Liver
Deferasirox Decreases Age-Associated Iron Accumulation in the Aging F344XBN Rat Heart and Liver
复制标题
DOI：
10.1007/s12012-010-9068-9
复制
发表时间：
2010-06-01
影响因子：
3.2
通讯作者：
Blough, Eric R.
中科院分区：
文献类型：
--
作者：
Arvapalli, Ravi Kumar;Paturi, Satyanarayana;Blough, Eric R.
人们认为，大鼠和人类的衰老与铁积累和细胞凋亡的增加有关。在这里，我们研究了老年F344XBN大鼠的心肌铁水平与细胞凋亡的关系，这些大鼠隔日口服铁络合剂(Deferasirox；100 mg/kg体重)，连续6个月。与6月龄成年动物相比，33月龄动物的心脏铁(+72%)、肝铁(+87%)、铁蛋白轻链(+59%)、二价金属转运蛋白-1(+56%)和TdT介导的dUTP缺口末端标记(TUNEL)阳性细胞数(4.3倍)增加(P<；0.05)。去铁西罗治疗降低了37%的心肌铁水平(P<；0.05)，这与TUNEL阳性细胞数量的减少有关。与年龄相关的细胞死亡增加伴随着Bax/Bcl2比率的增加，以及Bad、全长caspase-3和裂解caspase-3的数量的增加。Deferasirox使Bax/Bcl2比值降低17%(P<；0.05)，Bad、全长caspase-3、裂解caspase-3(19 KDa)和裂解caspase-3(17 KDa)的数量分别减少41、16、22和37%(P<；0.05)。综上所述，这些数据表明去铁罗可能在减少F344XBN大鼠模型中与年龄相关的铁蓄积和心肌细胞凋亡方面有效。
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.