PMID- 33816465
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220421
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 9
DP  - 2021
TI  - Graphene Oxide and Reduced Graphene Oxide Exhibit Cardiotoxicity Through the 
      Regulation of Lipid Peroxidation, Oxidative Stress, and Mitochondrial 
      Dysfunction.
PG  - 616888
LID - 10.3389/fcell.2021.616888 [doi]
LID - 616888
AB  - OBJECTIVE: 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) in vitro 
      and in vivo, as well as to investigate the underlying toxicity mechanisms. 
      METHODS: 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 in 
      vitro 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 in 
      vivo 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. RESULTS: rGO 
      was developed from GO following different doses of gamma irradiation. In vitro 
      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. In vivo 
      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. CONCLUSION: 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.
CI  - Copyright (c) 2021 Zhang, Cao, Wang, Wu and Wang.
FAU - Zhang, Jian
AU  - Zhang J
AD  - Department of Cardiovascular Center, The First Hospital of Jilin University, 
      Changchun, China.
FAU - Cao, Hong-Yan
AU  - Cao HY
AD  - Department of Cardiovascular Center, The First Hospital of Jilin University, 
      Changchun, China.
FAU - Wang, Ji-Qun
AU  - Wang JQ
AD  - Department of Cardiovascular Center, The First Hospital of Jilin University, 
      Changchun, China.
FAU - Wu, Guo-Dong
AU  - Wu GD
AD  - Department of Cardiovascular Center, The First Hospital of Jilin University, 
      Changchun, China.
FAU - Wang, Lin
AU  - Wang L
AD  - Department of Cardiovascular Center, The First Hospital of Jilin University, 
      Changchun, China.
LA  - eng
PT  - Journal Article
DEP - 20210318
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC8012771
OTO - NOTNLM
OT  - cardiotoxicity
OT  - graphene family nanomaterials
OT  - lipid peroxidation
OT  - mitochondrial dysfunction
OT  - oxidative stress
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/04/06 06:00
MHDA- 2021/04/06 06:01
PMCR- 2021/01/01
CRDT- 2021/04/05 06:09
PHST- 2020/10/13 00:00 [received]
PHST- 2021/01/04 00:00 [accepted]
PHST- 2021/04/05 06:09 [entrez]
PHST- 2021/04/06 06:00 [pubmed]
PHST- 2021/04/06 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2021.616888 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Mar 18;9:616888. doi: 10.3389/fcell.2021.616888. 
      eCollection 2021.