Objectives: This study assessed the protective effects of saturated hydrogen against CCl4-induced acute kidney injury (AKI) in mice, and investigated signaling pathways activated by exposure to saturated hydrogen.
Methods: A mouse model of CCl4-induced AKI was established; some mice were treated with saturated hydrogen. Levels of cystatin C and kidney injury molecule 1 were determined using enzyme-linked immunosorbent assays. Blood urea nitrogen and serum creatinine were measured on a fully automated biochemical analyzer. Interleukin-8, tumor necrosis factor-α, and interferon-γ in serum and kidney tissues were measured using enzyme-linked immunosorbent assays. Malondialdehyde, glutathione peroxidase, and superoxide dismutase in kidney tissues were measured using biochemical kits. Oxidative stress in kidney tissues was analyzed using nitrotyrosine staining. Expression levels of p-JAK2, p-STAT3, and p-p65 signal protein were assayed by immunohistochemistry and western blotting.
Results: Compared with untreated mice with CCl4-induced AKI, mice that were treated with saturated hydrogen exhibited improved renal function and reduced oxidative stress. Moreover, expression levels of p-JAK2, p-STAT3, and p-p65 were significantly reduced in mice treated with saturated hydrogen, compared with expression levels in untreated mice.
Conclusions: Treatment with saturated hydrogen can reduce oxidative stress and inflammatory cytokine activation, potentially through inhibition of JAK2/STAT3/p65 signaling, thereby protecting against AKI.
Keywords: JAK2/STAT3/p65; Saturated hydrogen; acute kidney injury; carbon tetrachloride; cystatin C; glutathione peroxidase; kidney injury molecule 1; malondialdehyde; oxidative stress; superoxide dismutase.