Abstract:

Aims: Limb ischaemia/reperfusion (LIR) occurs in various clinical conditions including critical limb ischaemia, abdominal aortic aneurysm, and traumatic arterial injury. Reperfusion of the acutely ischemic limb can lead to a systemic inflammation response and multiple organ dysfunction syndrome, further resulting in significant morbidity and mortality. Molecular hydrogen exhibits therapeutic activity for the treatment and prevention of many diseases. Our study investigated the possible therapeutic effects of hydrogen and its mechanism of action in a LIR-induced acute lung injury (ALI) model. Materials and methods: Limb ischaemia/-reperfusion model was established in mice. The hydrogen-saturated saline was administered by intraperitoneal injection. Protein level of nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase-1 (HO1) and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) was evaluated by immunohistochemistry staining and western blotting. Autophagy-related molecules were evaluated by western blotting. Malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by assay kits. Quantification of ceramides in lung was performed by high-performance liquid chromatography-tandem mass spectrometry. Key findings: Molecular hydrogen exhibited a protective effect on the LIR-induced ALI model. Hydrogen decreased malondialdehyde and increased superoxide dismutase activity in lung tissues. Additionally, hydrogen activated Nrf2 signalling in lung tissues. Hydrogen could inhibit the upregulation of autophagy in the present rodent model. Furthermore, ceramide was accumulated in lung tissues because of LIR; however, hydrogen altered the accumulation status. Significance: Molecular hydrogen was found to be therapeutically effective in the LIR-induced ALI model; the mechanisms of action included modulation of antioxidation and autophagy.

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https://doi.org/10.1016/j.lfs.2021.119659

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