Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis

En-Sheng Ji, Fu-Yang Yu, Ji-Ren An, Jian Zhou, Li-Fei Luo, Na Wang, Peng Guan, Shengchang Yang, Ya-Shuo Zhao, Zhi-Min Sun

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DOI: 10.1016/j.lfs.2019.04.005 DOI is the universal ID for this study.

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Aims Hydrogen gas (H2) has a diversity of effects such as anti-apoptotic, anti-inflammatory and anti-oxidative properties. However, molecular mechanism underlying the potential effect of H2 on chronic intermittent hypoxia (CIH) induced renal injury remains obscure. Materials and methods In the present study, adult male Sprague-Dawley rats were randomly allocated into four groups: control (CON) group, CIH group, CIH with H2 treatment (CIH + H2) group, and control with H2 treatment (CON + H2) group. Oxidative stress, autophagy and endoplasmic reticulum (ER) stress were detected to determine how H2 affected the renal function of CIH exposed rats. Key findings We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats. Meanwhile, CIH-induced endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated. Furthermore, relative higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated. Inhibition of mTOR may be involved in the upregulation of autophagy by H2. Finally, increased phosphorylation of p38 and JNK was involved in the CIH-induced pathological process. H2 could inhibit the activation of p38 and JNK, suggesting H2 played an active part in resisting renal injury via MAPK. Significance Taken together, our study reveals that H2 can ameliorate CIH-induced kidney injury by decreasing endoplasmic reticulum stress and activating autophagy through inhibiting oxidative stress-dependent p38 and JNK MAPK activation.

Publish Year 2019
Country China
Rank Positive
Journal Life Sciences
Primary Topic Kidney
Secondary TopicSleep Apnea
Model Rat
Tertiary TopicHypoxia-Ischemia
Vehicle Gas
pH N/A
Application Inhalation