In this article, we are going to learn about one more important benefit of hydrogen; it’s anti-apoptotic effect. Before we go in to detail, let’s get to know what apoptosis means.

What is apoptosis?

Apoptosis is the cell death that occurs normally in our body due to aging or as a controlled part of growth and development. This programmed cell death can occur as a result of various biochemical processes happening inside the cell. This is a form of a suicide due to activation of internal death mechanism.

So what does really happen when the cell is compelled to commit suicide? This will result in triggering various chemical processes in the body. The proteins known as caspases are triggered and they destroy the cell architecture. This in turn triggers an enzyme called DNAse which is able to break down DNA. The DNA is the genetic material in the nucleus of the cell which controls the whole cell. The damaged cell then starts shrinking gradually and more proteolytic enzymes are released to destroy the cell from inside. The cells develop bubble like blebs on the cell surface.

When the mitochondrion which is the power generator inside the cell is destroyed it releases cytochrome C. The cell also breaks into small fragments which are wrapped by a membrane. When the inside of the cell is getting destroyed, it releases chemicals which act as distress signals to the outside of the cell that it is dying. Some of them include ATP and UTP. ATP, a nucleotide and UTP, a nucleoside, are bind to phagocyte cells. These cells can take up and digest parts of tissue and other parts.

When the signals come to the phagocyte cells that a cell is dying, they try to go to that particular cell fragments. These cell fragments also expose phospholipids which are normally not exposed to the outside. This helps the macrophages to identify these fragments precisely and they start engulfing it. The phagocytes may secrete substances such as cytokines which can induce inflammation in the surrounding area.

However, in this process, the membrane of the cell stays intact. Therefore not much harm comes to the surrounding tissues. This is different to necrosis in which the cell dies due to trauma and injury. But here the cell membrane is damaged and all the toxic acting substances are released to the outside inducing lot of inflammation.

What is the role of apoptosis?

Apoptosis may occur when the cell naturally ages and “decides” its purpose is over. It may also occur when a foreign bacteria or virus invades the cell and the cell try to contain the infection by suicide.

However, apoptosis can occur in other disease too. When there is much oxidative stress the cells can undergo apoptosis. There are many diseases that show increased apoptosis as a part of their disease process. Alzheimer’s disease, Parkinson’s disease and AIDS and others have increased apoptosis. By using anti-apoptotics we can not only halt these disease processes but also combat aging process to certain extent.

How does hydrogen act as an antiapoptotic?

Since the publication of Ohta et al. on the effects of hydrogen in 2015, there have been many researches done to test the effectiveness of hydrogen against various diseases. In that first study itself, it was estimated that hydrogen contains anti-apoptotic properties via regulating gene expression of the cells. We have listed some of the studies in the appendix. Here I will summarize the scientific evidence that hydrogen is effective in fighting apoptosis detected in animal models.

Hydrogen inhalation has shown to exert antioxidant and anti-apoptotic effects and protect the brain in ischemia reperfusion injury. This does so by reducing the oxidative free radicals such as hydroxyl radical and peroxynitrite.

Hydrogen is also effective in reducing acute liver injury. When hydrogen rich saline was given to mice, the activity of substances which promotes apoptosis such as JNK and caspase-3 were inhibited. This can inhibit the death of cells in liver not only in acute injury, but also in liver cirrhosis and liver cell compensatory proliferation leading to liver disease.

The anti-apoptotic effect is also important in organ transplantation to reduce the death of cells. In intestinal grafts, hydrogen was shown to up regulate the anti-apoptotic protein called heme oxygenase 1. When the grafts were pre-treated with hydrogen before transplantation, the function was protected leading to superior survival rates in the recipients of the graft.

After a cardio-pulmonary bypass surgery, when there were given hydrogen as inhaled gas it resulted in positive outcomes and the researchers suggested this treatment as a new potential therapy.

Hydrogen can improve the survival rate in sepsis. It is important because sepsis remains one of the most common causes of death in critically ill patients in hospital settings. When hydrogen rich saline was given to animal models it has been found reduced apoptosis in addition to anti-inflammatory and anti-oxidant properties in reducing the impact of sepsis.

It is possible to experience heart burn when we are stressed. The stress induced gastric ulcers can be prevented by drinking hydrogen rich fluid. Hydrogen treatment can reduce the level of caspase in the stomach mucosa and reduce the damage to the gastric mucosa by preventing cell apoptosis.

Heart attacks are so common in present time. However, hydrogen rich saline has been shown to reduce the myocardial infarct size. Another group has found that hydrogen gas enhanced the recovery of left ventricular function following anoxia-reoxygenation (it means reperfusion usually caused a so called reperfusion injury). Hydrogen reduced the infarct size without altering hemodynamic parameters. Hydrogen gas also prevented left ventricular remodeling (the process of alteration of ventricular size, shape and function) after myocardial infarction.

Subarachnoid haemorrhage is considered a life threatening condition and it can cause death of brain cells. Hydrogen has been able to modify pathways leading to death especially via the Akt/GSK3β pathway. This reduces apoptosis of neurones in the brain and improves the outcome after subarachnoid haemorrhage.

Not only that, hydrogen also can act on lungs and reduce the cell death in lung injuries too. It induces anti-apoptotic genes. Anti-apoptotic protein Bcl 2 is upregulated by this way and the proteins which promote apoptosis such as Bax are down regulated.

Hydrogen has been shown to reduce apoptosis in the pancreas in case of an acute pancreas inflammation so that the risk for development of a diabetes mellitus is reduced.

In case of diabetic retinopathy the retinal apoptosis and vascular permeability biomarkers were reduced by hydrogen gas inhalation in a rat model. These results suggested a potential use of hydrogen for the treatment of this disease which often leads to blindness.

Hydrogen can be taken by inhalation of the gas, inhalation of an aerosol hydrogen-rich solution, injecting hydrogen-rich saline, taking a hydrogen bath and drinking hydrogen dissolved in water. For daily consumption, the most suitable method is drinking hydrogen enriched water or to inhale hydrogen gas generated by an electrolyser.

Although hydrogen is the most abundant chemical element in the universe, it is not used in the treatment of diseases in the therapeutic setting so far. However recent evidence on this amazing gas has changed all that. Hundreds of studies about hydrogen, so far mostly in an animal model, suggest to be effective in many diseases also in human. It can be assumed that we will see hydrogen in the clinics in recent future. It may be used also as anti-aging product due to its anti-apoptotic and anti-oxidative effects.

References

• Ohta, S., Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods Enzymol, 2015. 555: p. 289-317.
• Shen, M.H., et al., Hydrogen as a novel and effective treatment of acute carbon monoxide poisoning. Medical Hypotheses, 2010. 75(2): p. 235-237.
• Sun, H., et al., The protective role of hydrogen-rich saline in experimental liver injury in mice. Journal of Hepatology, 2011. 54(3): p. 471-80.
• Buchholz, B.M., et al., Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation. Transplantation, 2011. 92(9): p. 985-92.
• Li, G.M., et al., Effects of hydrogen-rich saline treatment on polymicrobial sepsis. Journal of Surgical Research, 2013. 181(2): p. 279-86.
• Liu, X., et al., The protective of hydrogen on stress-induced gastric ulceration. Int Immunopharmacol, 2012. 13(2): p. 197-203.
• Fujii, Y., et al., Insufflation of hydrogen gas restrains the inflammatory response of cardiopulmonary bypass in a rat model. Artif Organs, 2013. 37(2): p. 136-41.
• Zhang G, Gao S, Li X, et al. Pharmacological postconditioning with lactic acid and hydrogen rich saline alleviates myocardial reperfusion injury in rats. Sci Rep. 2015 Apr 30;5:9858.
• Bari, F., et al., Inhalation of Hydrogen Gas Protects Cerebrovascular Reactivity Against Moderate but Not Severe Perinatal Hypoxic Injury in Newborn Piglets. Stroke, 2010. 41(4): p. E323-E323.
• Hong, Y., et al., Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: possible role of the Akt/GSK3beta signalling pathway. PLoS One, 2014. 9(4): p. e96212.
• Huang, C.S., et al., Hydrogen inhalation ameliorates ventilator-induced lung injury. Critical Care, 2010. 14(6): p. R234.
• Li, Y.-P., Teruya, K., Katakura, Y., Kabayama, S., Otsubo, K.,Morisawa, S., et al, Effect of reduced water on the apoptotic cell death triggered by oxidative stress in pancreatic b HIT-T15 cell. Animal cell technology meets genomics, 2005: p. 121-124.
• Oharazawa, H., et al., Protection of the Retina by Rapid Diffusion of Hydrogen: Administration of Hydrogen-Loaded Eye Drops in Retinal Ischemia-Reperfusion Injury. Investigative Ophthalmology & Visual Science, 2010. 51(1): p. 487-492.
• Qu, J., et al., Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils. Acta Pharmacologica Sinica, 2012. 33(4): p. 445-451.
• Hayashida, K., Sano, M., Ohsawa, I., Shinmura, K., Tamaki, K., et al. (2008) Inhalation of Hydrogen Gas Reduces Infarct Size in the Rat Model of Myocardial Ischemia-Reperfusion Injury. Biochemical and Biomedical Research Communications, 373, 30-35.