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

AIMS

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

SIGNIFICANCE

Taken together, our study reveals that H can ameliorate CIH-induced kidney injury by decreasing endoplasmic reticulum stress and activating autophagy through inhibiting oxidative stress-dependent p38 and JNK MAPK activation.