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Research Paper|Volume 11, Issue 24|pp 12097—12113

Aerosol inhalation of a hydrogen-rich solution restored septic renal function

Weifeng Yao1, Anshun Guo1,2, Xue Han3, Shan Wu1, Chaojin Chen1, Chenfang Luo1, Haobo Li4, Shangrong Li1, Ziqing Hei1
  • 1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • 2Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
  • 3Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510000, China
  • 4Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524023, China
* Equal contribution
Received: May 3, 2019Accepted: November 19, 2019Published: December 16, 2019
https://doi.org/10.18632/aging.102542

Copyright © 2019 Yao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Sepsis-related acute kidney injury (AKI) is known to be caused by inflammation. We explored the renal protective effects of aerosol inhalation of a hydrogen-rich solution (HRS; hydrogen gas dissolved to saturation in saline) in a mouse model of septic AKI. Septic AKI was induced through 18 hours of cecal ligation and puncture. AKI occurred during the early stage of sepsis, as evidenced by increased blood urea nitrogen and serum creatinine levels, pathological changes, renal fibrosis and renal tubular epithelial cell apoptosis, accompanied by macrophage infiltration and M1 macrophage-associated pro-inflammatory cytokine (Il-6 and Tnf-α) generation in renal tissues. Aerosol inhalation of the HRS increased anti-inflammatory cytokine (Il-4 and Il-13) mRNA levels in renal tissues and promoted macrophage polarization to the M2 type, which generated additional anti-inflammatory cytokines (Il-10 and Tgf-β). Ultimately, aerosol inhalation of HRS protected the kidneys and increased survival among septic mice. HRS was confirmed to promote M2 macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The TGF-β1 receptor inhibitor SB-431542 partly reversed the effects of HRS on renal function, fibrosis, tubular epithelial cell apoptosis and senescence in mice. Thus, HRS aerosol inhalation appears highly useful for renal protection and inflammation reduction in septic AKI.