Almazov National Medical Research Centre, Ministry of Health of the Russian Federation, 197341 Saint-Petersburg, Russia.
Institute of Biomedical Systems and Biotechnologies, Peter the Great St. Petersburg Polytechnic University, 194021 Saint-Petersburg, Russia.
Int J Mol Sci. 2022 Oct 28;23(21):13096. doi: 10.3390/ijms232113096.
Doxorubicin, which is widely used to treat a broad spectrum of malignancies, has pronounced dose-dependent side effects leading to chronic heart failure development. Nicotinamide riboside (NR) is one of the promising candidates for leveling the cardiotoxic effect. In the present work, we performed a comparative study of the cardioprotective and therapeutic actions of various intravenous NR administration modes in chronic doxorubicin-induced cardiomyopathy in Wistar rats. The study used 60 mature male SPF Wistar rats. The animals were randomized into four groups (a control group and three experimental groups) which determined the doxorubicin (intraperitoneally) and NR (intravenous) doses as well as the specific modes of NR administration (combined, preventive). We demonstrated the protective effect of NR on the cardiovascular system both with combined and preventive intravenous drug administration, which was reflected in a fibrous tissue formation decrease, reduced fractional-shortening decrease, and better antioxidant system performance. At the same time, it is important to note that the preventive administration of NR had a more significant protective effect on the animal organism as a whole. This was confirmed by better physical activity parameters and vascular bed conditions. Thus, the data obtained during the study can be used for further investigation into chronic doxorubicin-induced cardiomyopathy prevention and treatment approaches.
多柔比星广泛用于治疗多种恶性肿瘤,具有明显的剂量依赖性副作用,导致慢性心力衰竭的发展。烟酰胺核糖(NR)是一种有前途的减轻心脏毒性作用的候选药物。在本工作中,我们对慢性多柔比星诱导的心肌病大鼠的各种静脉内 NR 给药方式的心脏保护和治疗作用进行了比较研究。研究使用了 60 只成熟雄性 SPF 白化 Wistar 大鼠。动物随机分为四组(对照组和三组实验组),确定了多柔比星(腹腔内)和 NR(静脉内)的剂量以及 NR 的具体给药方式(联合,预防)。我们证明了 NR 对心血管系统的保护作用,无论是联合还是预防性静脉内给药,都表现为减少纤维组织形成、减少分数缩短减少和更好的抗氧化系统性能。同时,值得注意的是,NR 的预防性给药对动物整体具有更显著的保护作用。这一点通过更好的身体活动参数和血管床状况得到了证实。因此,在研究过程中获得的数据可用于进一步研究慢性多柔比星诱导的心肌病的预防和治疗方法。