Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat
Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat
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DOI：
10.1007/s00395-010-0094-3
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发表时间：
2010-07-01
影响因子：
9.5
通讯作者：
Blough, Eric R.
中科院分区：
文献类型：
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作者：
Kakarla, Sunil K.;Fannin, Jacqueline C.;Blough, Eric R.
在快速增长的老年人口中，越来越需要药理学药物来管理心血管疾病。在这里，我们确定对乙酰氨基酚是否有效降低衰老的Fischer 344 X褐挪威大鼠心脏活性氧（ROS）和细胞凋亡的年龄相关增加。与6月龄对照动物相比，33月龄大鼠心脏氧化（超氧阴离子[O2 (euro cent-)]和4-羟基-2-壬烯醛[4-HNE]）和亚硝化（蛋白质硝基化）应激指标明显升高。33个月大的动物服用对乙酰氨基酚（30毫克/公斤/天，每天服用6个月），心脏ROS水平和TUNEL阳性细胞核的年龄相关性增加减少，这些变化伴随着Bax/Bcl2比率的改善，caspase-3活化的证据减少，蛋白激酶B、ERK1/2、p70S6K和GSK-3 β磷酸化的增加。综上所述，这些结果表明，对乙酰氨基酚可能通过降低与年龄相关的ROS生成升高来减弱与年龄相关的心肌细胞凋亡的增加。
There is a growing need for pharmacological agents to manage cardiovascular disease in the rapidly growing elderly population. Here, we determine if acetaminophen is efficacious in decreasing age-related increases in cardiac reactive oxygen species (ROS) and apoptosis in aging Fischer 344 X Brown Norway rats. Compared to 6-month control animals, indices of oxidative (superoxide anion [O2 (aEuro cent-)] and 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were markedly increased in 33-month-old rat hearts. 33-month animals that had been treated with acetaminophen (30 mg/kg/day p.o. for 6 months) exhibited diminished age-related increases in cardiac ROS levels and TUNEL positive nuclei and these changes were accompanied by improvements in the Bax/Bcl2 ratio, diminished evidence of caspase-3 activation and increased phosphorylation of protein kinase B, ERK1/2, p70S6K and GSK-3 beta. Taken together these results suggests that acetaminophen may attenuate the age-associated increases in the cardiomyocyte apoptosis, possibly via diminishing age associated elevation in ROS production.