Department of Medical Oncology, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey.
Department of Medical Oncology, Yozgat City Hospital, Yozgat, Turkey.
Hum Exp Toxicol. 2020 Aug;39(8):1046-1053. doi: 10.1177/0960327120909874. Epub 2020 Mar 5.
In this study, we aimed to show the effect of adenosine 5'-triphosphate (ATP) on sunitinib-induced cardiac injury in rats. The rats ( = 30) were divided equally into three groups as sunitinib group (SG), sunitinib plus ATP group (SAG), and healthy group (HG); 2 mg/kg ATP was injected intraperitoneally (ip) to the SAG group. Same volume normal saline as solvent was administered ip to the other two groups. After 1 h, 25 mg/kg sunitinib was applied orally via catheter to stomach in the SAG and SG groups. This procedure was repeated once daily for 5 weeks. At the end of this period, all animals were sacrificed and their cardiac tissue was removed. Malondialdehyde (MDA), total glutathione (tGSH), tumor necrosis factor (TNF-), and nuclear factor B (NF-B) levels in rats' cardiac tissues and troponin I (Tp-I) levels in rats' blood samples were evaluated. Histopathological analysis was also performed in cardiac tissues of the animals. MDA, TNF-, NF-B, and Tp-I levels were higher in the SG group compared to the SAG and HG groups ( < 0.001). tGSH levels of the SG group were lower than the SAG and HG groups ( < 0.001). The structure and morphology of cardiac muscle fibers and blood vessels were normal in the control group. In the SG group, obvious cardiac muscle tissue damage with dilated myofibers, locally atrophic myofibers, and congested blood vessels were observed. In the SAG group, marked amelioration in these findings was observed. We showed this for the first time that ATP administration exerts a protective effect against cardiac effects of sunitinib.
在这项研究中,我们旨在展示三磷酸腺苷(ATP)对大鼠舒尼替尼诱导的心脏损伤的影响。将大鼠(=30)平均分为三组:舒尼替尼组(SG)、舒尼替尼加 ATP 组(SAG)和健康组(HG);SAG 组腹腔内(ip)注射 2mg/kg ATP。另外两组则给予等体积的生理盐水作为溶剂。1 小时后,通过胃管给 SAG 和 SG 组大鼠口服 25mg/kg 舒尼替尼。该过程每周重复 5 次。在此期间结束时,所有动物被处死,取出其心脏组织。评估大鼠心脏组织中丙二醛(MDA)、总谷胱甘肽(tGSH)、肿瘤坏死因子(TNF-)和核因子 B(NF-B)水平以及大鼠血液样本中的肌钙蛋白 I(Tp-I)水平。还对动物心脏组织进行了组织病理学分析。与 SAG 和 HG 组相比,SG 组 MDA、TNF-、NF-B 和 Tp-I 水平更高(<0.001)。SG 组的 tGSH 水平低于 SAG 和 HG 组(<0.001)。对照组的心肌纤维和血管结构和形态正常。在 SG 组中,观察到明显的心肌组织损伤,包括扩张的肌纤维、局部萎缩的肌纤维和充血的血管。在 SAG 组中,这些发现明显得到改善。我们首次表明,ATP 给药对舒尼替尼的心脏作用具有保护作用。