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

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.

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.

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.

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.