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

Weifeng Yao,Xue Han,Shan Wu,Ziqing Hei,Anshun Guo,Haobo Li,Shangrong Li,Chaojin Chen,Chenfang Luo

doi:10.18632/aging.102542

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.

Highlights

During sepsis, the inflammatory process will become increasingly severe and lead to organ dysfunction if sepsis cannot be halted [1]
Arterial blood gas analysis (Table 1) revealed that the partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were slightly higher in mice administered the hydrogen-rich solution (HRS) than in those administered saline by aerosol inhalation, but the difference was not statistically significant (P>0.05). These results indicated that aerosol inhalation of a HRS is a feasible and safe method of delivering hydrogen without irritating the respiratory tract or reducing PaO2 levels
We evaluated the safety and effectiveness of aerosol inhalation of an HRS in septic acute kidney injury (AKI)

Summary

Introduction

The inflammatory process will become increasingly severe and lead to organ dysfunction if sepsis cannot be halted [1]. 70% of septic AKI cases are fatal; kidney protection is greatly important for the survival of sepsis patients [2]. An excessive inflammatory response and oxidative stress are considered to be the main mechanisms of septic AKI [9, 10]. Inflammation resolution is an important endogenous protective mechanism that can restore homeostasis and limit excessive tissue damage in response to injury [11, 12]. Promoting inflammation resolution was found to be critical for comprehensive sepsis therapy, suggesting a new therapeutic concept for preventing septic AKI [15]. Macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 macrophages has been identified as a key mechanism of inflammation resolution, and is an attractive target for septic AKI prevention [16]

Methods

Results

Conclusion