High concentration hydrogen attenuates sepsis-induced acute kidney injury by promoting mitochondrial biogenesis and fusion

Abstract

Sepsis is a major cause of mortality among critical patients. Acute kidney injury (AKI) is the common complication in patients with sepsis, characterized by rapid deterioration of renal function. The purpose of this study is to assess the impact of inhaling high concentration hydrogen on septic mice with AKI and to examine the involvement of mitochondria in this process. High concentration hydrogen does not cause hypoxia and can alleviate AKI and improve 7-day survival in septic mice. Inflammatory factors are markedly elevated in the serum and renal tissues in CLP group which are dramatically down-regulated by hydrogen. The activities of both antioxidant enzymes are significantly reduced after CLP, whereas hydrogen markedly increases the activities of SOD and CAT. MMP is found to be significantly lower in CLP group whereas this effect is reversed by hydrogen. The trend of ATP content in renal tissues corresponded with that of MMP. There is a substantial downregulation of PGC-1α, Nrf2, and TFAM protein in CLP group. Drp1 expression is significantly higher in CLP group compared to Sham group, while the opposite trend is observed for MFN2. Hydrogen can reverse these changes. Inhalation of high concentration hydrogen can improve acute kidney injury, 7-day survival, inflammatory response and oxidative stress in septic mice. The mechanism may be related to inhibit renal mitochondrial fission and promote mitochondrial fusion and biogenesis.

Study details

Article type

Original Research

Disease / injury model

Sepsis-induced acute kidney injury (AKI) in mice (CLP model)

Duration

7 days

Dose-dependent effect

No

Outcome

Positive

Findings

High concentration hydrogen inhalation significantly attenuates sepsis-induced acute kidney injury, improves 7-day survival, reduces inflammatory cytokines, enhances antioxidant enzyme activities, and promotes mitochondrial biogenesis and fusion in septic mice.