Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 620014 Yekaterinburg, Russia.
Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, 620049 Yekaterinburg, Russia.
Int J Mol Sci. 2021 Mar 27;22(7):3466. doi: 10.3390/ijms22073466.
Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO-NP and PbO-NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β-MHC. The type of CdO-NP + PbO-NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb-NP and CdO-NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.
亚慢性中毒是通过向雄性大鼠反复腹腔内注射氧化铅(PbO)和/或氧化镉(CdO)纳米颗粒(NPs)3 次/周,持续 6 周而诱导的,目的是研究其对右心室游离壁和乳头肌在等长和后负荷收缩时的收缩特性的影响。观察到单独和联合使用这些 NPs 会降低这两种心肌制剂产生的机械功。使用体外运动检测,我们表明,在 CdO-NP 和 PbO-NP 的单独和联合中毒下,调节的薄丝滑动速度下降。这些结果与肌球蛋白重链(MHC)同工型向缓慢循环的β-MHC 表达的转变相关。CdO-NP+PbO-NP 联合心脏毒性的类型取决于毒性影响的类型、影响的程度、有毒物质剂量的比例以及所研究的心肌细胞和肌肉类型的拉伸程度。如果在生物保护复合物的背景给药下发生中毒,某些联合 Pb-NP 和 CdO-NP 心脏毒性和一般毒性(包括遗传毒性)的指标完全或部分恢复正常。