Zhang Jian, Cao Hong-Yan, Wang Ji-Qun, Wu Guo-Dong, Wang Lin
Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China.
Front Cell Dev Biol. 2021 Mar 18;9:616888. doi: 10.3389/fcell.2021.616888. eCollection 2021.
Graphene has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to evaluate the cardiotoxicity of graphene oxide (GO) and reduced GO (rGO) and , as well as to investigate the underlying toxicity mechanisms.
GO was reduced by gamma irradiation to prepare rGO and then characterized by UV/visible light absorption spectroscopy. Rat myocardial cells (H9C2) were exposed to GO or rGO with different absorbed radiation doses. The cytotoxicity was evaluated by MTT assay, cell apoptosis assay, and lactate dehydrogenase (LDH) activity assay. The effects of GO and rGO on oxidative damage and mitochondrial membrane potential were also explored in H9C2 cells. For experiments, mice were injected with GO or rGO. The histopathological changes of heart tissues, as well as myocardial enzyme activity and lipid peroxidation indicators in heart tissues were further investigated.
rGO was developed from GO following different doses of gamma irradiation. experiments in H9C2 cells showed that compared with control cells, both GO and rGO treatment inhibited cell viability, promoted cell apoptosis, and elevated the LDH release. With the increasing radiation absorbed dose, the cytotoxicity of rGO gradually increased. Notably, GO or rGO treatment increased the content of ROS and reduced the mitochondrial membrane potential in H9C2 cells. experiments also revealed that GO or rGO treatment damaged the myocardial tissues and changed the activities of several myocardial enzymes and the lipid peroxidation indicators in the myocardial tissues.
GO exhibited a lower cardiotoxicity than rGO due to the structure difference, and the cardiotoxicity of GO and rGO might be mediated by lipid peroxidation, oxidative stress, and mitochondrial dysfunction.
由于其独特的物理化学性质，石墨烯已被广泛应用于各种生物和生物医学领域。本研究旨在评估氧化石墨烯（GO）和还原氧化石墨烯（rGO）的心脏毒性，并探究其潜在的毒性机制。
通过γ射线辐照还原GO制备rGO，然后用紫外/可见光吸收光谱对其进行表征。将大鼠心肌细胞（H9C2）暴露于不同吸收辐射剂量的GO或rGO中。通过MTT法、细胞凋亡检测和乳酸脱氢酶（LDH）活性检测评估细胞毒性。还在H9C2细胞中探究了GO和rGO对氧化损伤和线粒体膜电位的影响。在动物实验中，给小鼠注射GO或rGO。进一步研究心脏组织的组织病理学变化以及心脏组织中的心肌酶活性和脂质过氧化指标。
不同剂量的γ射线辐照后，GO生成了rGO。H9C2细胞实验表明，与对照细胞相比，GO和rGO处理均抑制细胞活力、促进细胞凋亡并提高LDH释放。随着吸收辐射剂量的增加，rGO的细胞毒性逐渐增加。值得注意的是，GO或rGO处理增加了H9C2细胞中活性氧（ROS）的含量并降低了线粒体膜电位。动物实验还表明，GO或rGO处理损害了心肌组织，并改变了心肌组织中几种心肌酶的活性和脂质过氧化指标。
由于结构差异，GO的心脏毒性低于rGO，且GO和rGO的心脏毒性可能由脂质过氧化、氧化应激和线粒体功能障碍介导。
