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

Aims: Hydrogen gas (H-2) has a diversity of effects such as anti-apoptotic, anti-inflammatory and anti-oxidative properties. However, molecular mechanism underlying the potential effect of H-2 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 H-2 treatment (CIH + H-2) group, and control with H-2 treatment (CON + H-2) group. Oxidative stress, autophagy and endoplasmic reticulum (ER) stress were detected to determine how H-2 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 H-2 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 H-2 administrated. Inhibition of mTOR may be involved in the upregulation of autophagy by H-2. Finally, increased phosphorylation of p38 and JNK was involved in the CIH-induced pathological process. H-2 could inhibit the activation of p38 and JNK, suggesting H-2 played an active part in resisting renal injury via MAPK. Significance: Taken together, our study reveals that H-2 can ameliorate CIH-induced kidney injury by decreasing endoplasmic reticulum stress and activating autophagy through inhibiting oxidative stress-dependent p38 and JNK MAPK activation.