Graphene oxide induces dose‑dependent lung injury in rats by regulating autophagy

  • Authors:
    • Lei Zhang
    • Shuge Ouyang
    • Hongbo Zhang
    • Mingke Qiu
    • Yuxin Dai
    • Shuqing Wang
    • Yang Wang
    • Jingmin Ou
  • View Affiliations

  • Published online on: March 5, 2021     https://doi.org/10.3892/etm.2021.9893
  • Article Number: 462
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Abstract

Graphene is a two‑dimensional structured material with a hexagonal honeycomb lattice composed of carbon atoms. The biological effects of graphene oxide (GO) have been extensively investigated, as it has been widely used in biological research due to its increased hydrophilicity/biocompatibility. However, the exact mechanisms underlying GO‑associated lung toxicity have not yet been fully elucidated. The aim of the present study was to determine the role of GO in lung injury induction, as well as its involvement in oxidative stress, inflammation and autophagy. The results revealed that lower concentrations of GO (5 and 10 mg/kg) did not cause significant lung injury, but the administration of GO at higher concentrations (50 and 100 mg/kg) induced lung edema, and increased lung permeability and histopathological lung changes. High GO concentrations also induced oxidative injury and inflammatory reactions in the lung, demonstrated by increased levels of oxidative products [malondialdehyde(MDA) and 8‑hydroxydeoxyguanosine (8‑OHdG)] and inflammatory factors (TNF‑α, IL‑6, IL‑1β and IL‑8). The autophagy inhibitors 3‑methyladenine (3‑MA) and chloroquine (CLQ) inhibited autophagy in the lung and attenuated GO‑induced lung injury, as demonstrated by a reduced lung wet‑to‑dry weight ratio, lower levels of protein in the bronchoalveolar lavage fluid, and a reduced lung injury score. Furthermore, 3‑MA and CLQ significantly reduced the levels of MDA, 8‑OHdG and inflammatory factors in lung tissue, suggesting that autophagy also mediates the development of oxidative injury and inflammation in the lung. Finally, autophagy was directly inhibited in BEAS‑2B cells by short hairpin RNA‑mediated autophagy protein 5 (ATG5) knockdown, which were then treated with GO. Cell viability, as well as the extent of injury (indicated by lactate dehydrogenase level) and oxidative stress were determined. The results revealed that ATG5 knockdown‑induced autophagic inhibition significantly decreased cellular injury and oxidative stress, suggesting that autophagy induction is a key event that leads to lung injury during exposure to GO. In conclusion, the findings of the present study indicated that GO causes lung injury in a dose‑dependent manner by inducing autophagy.
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May-2021
Volume 21 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang L, Ouyang S, Zhang H, Qiu M, Dai Y, Wang S, Wang Y and Ou J: Graphene oxide induces dose‑dependent lung injury in rats by regulating autophagy. Exp Ther Med 21: 462, 2021
APA
Zhang, L., Ouyang, S., Zhang, H., Qiu, M., Dai, Y., Wang, S. ... Ou, J. (2021). Graphene oxide induces dose‑dependent lung injury in rats by regulating autophagy. Experimental and Therapeutic Medicine, 21, 462. https://doi.org/10.3892/etm.2021.9893
MLA
Zhang, L., Ouyang, S., Zhang, H., Qiu, M., Dai, Y., Wang, S., Wang, Y., Ou, J."Graphene oxide induces dose‑dependent lung injury in rats by regulating autophagy". Experimental and Therapeutic Medicine 21.5 (2021): 462.
Chicago
Zhang, L., Ouyang, S., Zhang, H., Qiu, M., Dai, Y., Wang, S., Wang, Y., Ou, J."Graphene oxide induces dose‑dependent lung injury in rats by regulating autophagy". Experimental and Therapeutic Medicine 21, no. 5 (2021): 462. https://doi.org/10.3892/etm.2021.9893