Early changes in myocardial antioxidant enzymes in rats treated with adriamycin
Early changes in myocardial antioxidant enzymes in rats treated with adriamycin
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DOI：
10.1023/a:1014862912783
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发表时间：
2002-03-01
影响因子：
4.3
通讯作者：
Singal, PK
中科院分区：
文献类型：
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作者：
Li, T;Danelisen, I;Singal, PK
增加氧化应激和抗氧化剂缺陷已被认为在阿霉素诱导的心肌病和充血性心力衰竭中起主要作用，由于阿霉素（阿霉素）的多次治疗。在这项研究中，我们研究了单剂量阿霉素对大鼠心肌抗氧化酶的急性影响。将阿霉素（2.5mg/kg）注射（i. p.）分别于1、2、4和24 h检测心肌抗氧化酶活性、mRNA丰度和蛋白水平。锰超氧化物歧化酶（MnSOD），谷胱甘肽过氧化物酶（GSHPx）和过氧化氢酶（CAT）的活性没有显着变化，铜锌超氧化物歧化酶（CuZnSOD）的活性在所有时间点降低，这种变化与其蛋白质含量的减少。CuZnSOD mRNA在1和24 h时表达增加。GSHPx mRNA和蛋白水平在2 h分别短暂下降20%和25%。MnSOD mRNA表达无明显变化，但其蛋白水平在1h时明显下降。脂质过氧化反应在1、2和4 h时短暂增加。抗氧化酶的短暂抑制以及单剂量阿霉素的氧化应激的短暂增加可能先于药物重复给药所见的更持续的变化，并导致心肌病和心力衰竭的发展。
Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin-induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin (doxorubicin). In this study, we investigated the acute effects of a single dose of adriamycin on myocardial antioxidant enzymes in rats. Adriamycin (2.5 mg/kg) was injected (i.p.) and myocardial antioxidant enzyme activities, mRNA abundance and protein levels at 1, 2, 4 and 24 h were examined. While manganese superoxide dismutase (MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities were not significantly changed, copper-zinc superoxide dismutase (CuZnSOD) activity was reduced at all time points and this change correlated with a decrease in its protein content. CuZnSOD mRNA was increased at 1 and 24 h. GSHPx mRNA and protein levels were transiently decreased by 20 and 25% respectively at 2 h. MnSOD mRNA was not significantly changed, but its protein levels were significantly decreased at 1 h. Lipid peroxidation was increased transiently at 1, 2 and 4 h. A transient depression in antioxidant enzyme as well as transient increase in oxidative stress with a single dose of adriamycin may precede more sustained changes seen with the repeated administration of the drug and contribute to the development of cardiomyopathy and heart failure.