Bellini O, Danesi R, Bernardini N, Cardini G, Marzilli M, del Tacca M
Farmitalia-Carlo Erba Research Institute, Via Giovanni XXIII, Milano, Italy.
Anticancer Res. 1988 Jul-Aug;8(4):599-604.
A morphometric study was performed in dog atria to assess the effects of both single and repeated doses of doxorubicin on specific granules containing the natriuretic factor. Male beagle dogs were divided into 4 groups and treated i.v. as follows: groups A and B were controls and received isotonic saline; group C was given doxorubicin 2.4 mg/kg in a single injection; group D received doxorubicin 1.2 mg/kg once a week for 3 consecutive weeks. Samples of left atrium were taken 8 hours (groups A and C) or 28 days (groups B and D) after the last dose, and examined by the electron microscope. Compared with controls, the atrial tissue of group C dogs showed a significant increase in the number of specific granules; by contrast, the granularity was found to decrease significantly in the atria from group D dogs. These observations indicate a significant biphasic effect of doxorubicin on specific atrial granules of dog heart. The increase in granule density might be due to a block of the secretory process which is dependent on the metabolic energy supply. The reduction in cardiomyocyte granularity may be ascribed to the impairment of nucleic acid and protein synthesis induced by doxorubicin. Such alterations may play a significant role in doxorubicin-induced cardiovascular toxicity.
对犬心房进行了一项形态计量学研究，以评估单次和重复剂量的阿霉素对含有利钠因子的特定颗粒的影响。雄性比格犬分为4组，静脉注射给药，具体如下：A组和B组为对照组，接受等渗盐水；C组单次注射阿霉素2.4mg/kg；D组连续3周每周注射阿霉素1.2mg/kg。在最后一剂给药后8小时（A组和C组）或28天（B组和D组）采集左心房样本，并用电子显微镜检查。与对照组相比，C组犬的心房组织中特定颗粒数量显著增加；相比之下，发现D组犬心房中的颗粒度显著降低。这些观察结果表明阿霉素对犬心脏特定心房颗粒有显著的双相作用。颗粒密度增加可能是由于依赖代谢能量供应的分泌过程受阻。心肌细胞颗粒度降低可能归因于阿霉素诱导的核酸和蛋白质合成受损。这种改变可能在阿霉素诱导的心血管毒性中起重要作用。
