Recent Advances in Studies of Molecular Hydrogen against Sepsis

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Int. J. Biol. Sci. 2019, Vol. 15 1261 Ivyspring International Publisher International Journal of Biological Sciences 2019; 15(6): 1261-1275. doi: 10.7150/ijbs.30741 Review Recent Advances in Studies of Molecular Hydrogen against Sepsis Peng Qiu1, Yang Liu2, and Jin Zhang1 1. Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China 2. Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China Corresponding author: Jin Zhang, Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China. E-mail: Tel.: +86 18940259646 © Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions. Received: 2018.11.27; Accepted: 2019.01.09; Published: 2019.05.11 Abstract Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. Molecular hydrogen is a new type of antioxidant with strong free radical scavenging ability, which has been demonstrated to be effective for treating various diseases, such as infection, trauma, poisoning, organ ischemia-reperfusion, metabolic diseases, and tumors. Molecular hydrogen exerts multiple biological effects involving anti-inflammation, anti-oxidation, anti-apoptosis, anti-shock, and autophagy regulation, which may attenuate the organ and barrier damage caused by sepsis. However, the underlying molecular mechanisms remain elusive, but are likely related to the signaling pathways involved. This review focuses on the research progress and potential mechanisms of molecular hydrogen against sepsis to provide a theoretical basis for clinical treatment. Key words: molecular hydrogen, sepsis, oxidative stress, apoptosis, shock, autophagy Introduction Sepsis is a serious systemic inflammatory response syndrome caused by infection, which is characterized by an explosive inflammatory reaction, oxidative stress, and immune system disorder, that eventually leads to septic shock and multiple organ failure[1]. At present, there are several treatments for sepsis, such as anti-inflammation and anti-shock. However, there is no definite therapeutic effect and the mortality rate remains high. Molecular hydrogen was first reported in Nature Medicine (2007) as a natural antioxidant and selective scavenger of oxygen free radicals to treat oxidative stress [2]. A large number of studies have subsequently used it to treat various types of diseases, including infection, trauma, metabolic diseases, organ ischemia-reperfusion injury, and tumors and have achieved satisfactory efficacy[3]. Molecular hydrogen provides a variety of advantages for treating diseases due to its unique physical and chemical properties. There are three main forms of molecular hydrogen for research: hydrogen rich saline/water (HRS/W), inhaled hydrogen and hydrogen rich medium (HRM). Molecular hydrogen is safe, non-toxic and can balance the pH of body fluids[4]. Because of its small molecular weight, molecular hydrogen spreads easily and penetrates membranes into the cytoplasm, mitochondria, and even the nucleus [4]. Molecular hydrogen is non-flammable and non-explosive at the therapeutic concentration. Its effect is moderate and its metabolites are non-toxic. Although it has antioxidant capacity, molecular hydrogen does not interfere with normal metabolism or redox reactions [5]. In addition, molecular hydrogen promotes cell detoxification, increases cell hydration, and strengthens the host immune system[5]. Current studies have indicated that molecular hydrogen exerts its biological effects in two ways, one of which is reacting with hydroxyl radicals and per- oxynitrite directly, and the other is modulating speci- fic gene expression or signaling pathways[3] (Fig. 1).

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