Open Access

Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway

  • Authors:
    • Yao Xue
    • Yunqian Zhang
    • Li Chen
    • Yan Wang
    • Zhou Lv
    • Li-Qiao Yang
    • Siyuan Li
  • View Affiliations

  • Published online on: August 22, 2022     https://doi.org/10.3892/etm.2022.11569
  • Article Number: 632
  • Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI) is a common complication in patients with sepsis and is accompanied by high mortality. The present study aimed to investigate if the organic compound citrulline has a protective against lipopolysaccharide (LPS)‑stimulated ALI and its potential mechanisms. ALI was induced in mice by intraperitoneal (i.p.) injection of LPS (10 mg/kg). Citrulline (1 g/kg/day) was administrated i.p. 7 days prior to LPS injection. Mouse lung vascular endothelial cells (MLVECs) were divided into five groups: Control, LPS, LPS + Cit, LPS + N‑acetyl‑L‑cysteine (NAC) and LPS + Cit + ML385. Lung injury was determined by morphology changes. Apoptosis and pyroptosis were detected using western blot analysis and immunofluorescence. The present results indicated that citrulline can significantly attenuate ALI. Citrulline pretreatment decreased the expression of NOD‑, LRR‑ and pyrin domain‑containing protein 3 (NLRP3) inflammasome and decreased pyroptosis and apoptosis. Intervention with the total reactive oxygen species (ROS) scavenger N‑acetyl‑L‑cysteine attenuated NLRP3 inflammasome‑associated pyroptosis and apoptosis in LPS‑treated MLVECs. Citrulline pretreatment inhibited pyroptotic cell death and apoptosis induced by LPS. Citrulline decreased accumulation of intracellular ROS and activated the nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling pathway. Furthermore, the Nrf2 inhibitor ML385 reversed ROS generation, NLRP3 inflammasome‑mediated pyroptosis and apoptosis suppressed by citrulline. In summary, the present data demonstrated that citrulline may confer protection against ALI via inhibition of ROS/NLRP3 inflammasome‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway.

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October-2022
Volume 24 Issue 4

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

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Spandidos Publications style
Xue Y, Zhang Y, Chen L, Wang Y, Lv Z, Yang L and Li S: Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway. Exp Ther Med 24: 632, 2022
APA
Xue, Y., Zhang, Y., Chen, L., Wang, Y., Lv, Z., Yang, L., & Li, S. (2022). Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway. Experimental and Therapeutic Medicine, 24, 632. https://doi.org/10.3892/etm.2022.11569
MLA
Xue, Y., Zhang, Y., Chen, L., Wang, Y., Lv, Z., Yang, L., Li, S."Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 24.4 (2022): 632.
Chicago
Xue, Y., Zhang, Y., Chen, L., Wang, Y., Lv, Z., Yang, L., Li, S."Citrulline protects against LPS‑induced acute lung injury by inhibiting ROS/NLRP3‑dependent pyroptosis and apoptosis via the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 24, no. 4 (2022): 632. https://doi.org/10.3892/etm.2022.11569