Hydrogen molecules (H2) improve perfusion recovery via antioxidant effects in experimental peripheral arterial disease

Fu,Jinrong; Zou,Jinjing; Chen,Cheng; Li,Hongying; Wang,Lei; Zhou,Yanli

doi:10.3892/mmr.2018.9546

Hydrogen molecules (H2) improve perfusion recovery via antioxidant effects in experimental peripheral arterial disease

Authors:
- Jinrong Fu
- Jinjing Zou
- Cheng Chen
- Hongying Li
- Lei Wang
- Yanli Zhou
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Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Respiratory Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Gynecology, Hubei Maternal and Child Hospital, Wuhan, Hubei 430070, P.R. China, Department of Cardiology, Hubei University of Chinese Medicine, Wuhan, Hubei 430060, P.R. China
Published online on: October 10, 2018 https://doi.org/10.3892/mmr.2018.9546
Pages: 5009-5015
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Reactive oxygen species (ROS) impair neovascularization and perfusion recovery following limb ischemia in patients with peripheral arterial disease (PAD). Hydrogen molecules (H2) comprise an antioxidant gas that has been reported to neutralize cytotoxic ROS. The present study investigated whether H2 may serve as a novel therapeutic strategy for PAD. H2‑saturated water or dehydrogenized water was supplied to mice with experimental PAD. Laser Doppler perfusion imaging demonstrated that H2‑saturated water improved perfusion recovery, decreased the rate of necrosis, increased the capillary density in the gastrocnemius muscle and increased the artery density in the abductor muscle in the ischemic limbs, at 14 and 21 days post‑hindlimb ischemia. Ischemic muscle tissue was harvested 7 days after experimental PAD for biochemical testing and H2 was observed to reduce the levels of malondialdehyde and increase the levels of cyclic guanine monophosphate (cGMP). In cultured endothelial cells, H2‑saturated culture medium resulted in reduced ROS levels, increased tube formation and increased cGMP levels. In macrophages, H2 decreased cellular ROS levels and promoted M2 polarization. H2‑saturated water increases angiogenesis and arteriogenesis and subsequently improves perfusion recovery in a mouse PAD model via reduction of ROS levels.

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