Maita Rosa, Strauss Mirian, Anselmi Guillermo
Sección de Biología Celular, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
J Toxicol Pathol. 2009 Dec;22(4):273-9. doi: 10.1293/tox.22.273. Epub 2009 Dec 21.
In the present study, we compared the cell damage response in skeletal and cardiac muscle tissue when exposed to doxorubicin. This was carried out by means of a less invasive informative substitute to endomyocardiac biopsy based on Hsp70 immunodetection and a subcellular analysis of the nucleolus. Male Sprague Dawley rats (62 g body weight) were randomly distributed into 3 group, the control and doxorubicin I and doxorubicin II groups, in which 15 and 25 mg/kg body weight of doxorubicin (0.1 ml, i.v.) was administered, respectively. After 15, 30, 45 and 60 minutes, portions of the left and right ventricle wall and interventricle wall, together with skeletal muscle from the posterior and anterior member, were prepared for Hsp70 immunodetection by Western blot analysis and ultrastructural study using the thin cut technique. Differential cell response between the control and treated groups was observed in Hsp70 immunodetection and at the subcellular level. In the control group, the Hsp70 recognition levels and typical normal nucleolar morphology were similar, while the treated groups showed variable-dependent Hsp70 recognition and segregation of nucleolar components, forming ring-like figures of a variable-independent nature. Comparison of cardiac and skeletal muscle tissue cell response to doxorubicin toxic aggression revealed parallelism in terms of Hsp70 accumulation in certain regions of both tissues (15 mg/kg body weight of doxorubicin), which suggests that replacing endomyocardiac biopsy analysis with skeletal muscle analysis may be a safe option.
在本研究中,我们比较了骨骼肌和心肌组织在暴露于阿霉素时的细胞损伤反应。这是通过一种基于热休克蛋白70(Hsp70)免疫检测和核仁亚细胞分析的侵入性较小的信息替代方法来进行的,以替代心内膜心肌活检。雄性Sprague Dawley大鼠(体重62克)被随机分为3组,即对照组、阿霉素I组和阿霉素II组,分别给予15毫克/千克体重和25毫克/千克体重的阿霉素(0.1毫升,静脉注射)。在15、30、45和60分钟后,取左右心室壁和室间隔壁的部分组织,以及前后肢的骨骼肌,通过蛋白质免疫印迹分析进行Hsp70免疫检测,并使用超薄切片技术进行超微结构研究。在Hsp70免疫检测和亚细胞水平上观察到了对照组和处理组之间的细胞反应差异。在对照组中,Hsp70识别水平和典型的正常核仁形态相似,而处理组则表现出与剂量相关的Hsp70识别和核仁成分的分离,形成了与剂量无关的环状结构。比较心肌和骨骼肌组织细胞对阿霉素毒性攻击的反应发现,在两种组织的某些区域(15毫克/千克体重的阿霉素)中,Hsp70积累具有相似性,这表明用骨骼肌分析替代心内膜心肌活检分析可能是一种安全的选择。