In this article we will learn about another important benefit of hydrogen; it's anti-apoptotic effect. Before we go into detail, let's know what apoptosis means.

What is apoptosis?

Apoptosis is the cell death that normally occurs in our bodies due to ageing or as a controlled part of growth and development. This programmed cell death can occur as a result of various biochemical processes within the cell. It is a form of suicide through the activation of the internal death mechanism.

So what really happens when the cell is forced to commit suicide?

This leads to various chemical processes being triggered in the body. Proteins known as caspases are triggered and destroy the cell architecture. This in turn triggers an enzyme called DNAse, which is able to degrade DNA. DNA is the genetic material in the cell nucleus that controls the entire cell. The damaged cell then gradually begins to shrink and more proteolytic enzymes are released, destroying the cell from within. Bubble-like spots form on the cell surface.

When the mitochondrion, the energy generator inside the cell, is destroyed, cytochrome C is released and the cell disintegrates into small fragments that are enveloped by a membrane. When the inside of the cell is destroyed, it releases chemicals that act as distress signals to the outside of the cell that it is dying. Some of these are ATP and UTP. ATP, a nucleotide, and UTP, a nucleoside, are bound to phagocytic cells. These cells can ingest and digest parts of the tissue and other parts.

When the signals come to the phagocyte cells that a cell is dying, they try to get to those particular cell fragments. These cell fragments also expose phospholipids that are not normally visible to the outside. This helps the macrophages to accurately identify these fragments and they begin to engulf them. The scavenger cells can secrete substances such as cytokines that can trigger inflammation in the surrounding area.

However, the cell membrane remains intact during this process. Therefore, there is no great damage to the surrounding tissue. This is different from necrosis, where the cell dies due to trauma and injury. But here, the cell membrane is damaged and all the toxic substances are released to the outside, causing a lot of inflammation.

What is the role of apoptosis?

Apoptosis can occur when the cell naturally ages and "decides" that its purpose has been fulfilled. It can also occur when a foreign bacteria or virus invades the cell and the cell tries to contain the infection by committing suicide.

Apoptosis can also occur in other diseases. When there is a lot of oxidative stress, cells can undergo apoptosis. There are many diseases that show increased apoptosis as part of their disease process. Alzheimer's disease, Parkinson's disease and AIDS and others have increased apoptosis. By using anti-apoptotic drugs, we can not only stop these disease processes, but also fight the ageing process to some extent.

How does hydrogen work as an anti-apoptotic?

Since the publication of Ohta et al. on the effect of hydrogen in 2015, many studies have been conducted to test the effectiveness of hydrogen against various diseases. Even in this first study, hydrogen was estimated to have anti-apoptotic properties via regulating the gene expression of cells. We have listed some of the studies in the appendix. Here I will summarise the scientific evidence for the effectiveness of hydrogen in combating apoptosis that has been demonstrated in animal models.

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

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

The anti-apoptotic effect is also important in organ transplants to reduce cell death. In intestinal grafts, hydrogen has been shown to upregulate the anti-apoptotic protein haem oxygenase 1. When grafts were pre-treated with hydrogen prior to transplantation, function was protected, resulting in better survival rates in graft recipients.

When hydrogen was administered as an inhalation gas after cardio-pulmonary bypass surgery, this led to positive results, and the researchers suggested this treatment as a new potential therapy.

Hydrogen can improve survival in sepsis. This is important because sepsis remains one of the leading causes of death in critically ill patients in hospital. When hydrogen-rich saline was administered to animal models, it was found to reduce apoptosis in addition to its anti-inflammatory and antioxidant properties, thereby reducing the effects of sepsis.

It is possible to experience heartburn when we are stressed. The stress-induced stomach ulcers can be prevented by drinking hydrogen-rich fluids. Hydrogen treatment can reduce the level of caspase in the stomach lining and reduce the damage to the stomach lining by preventing cell apoptosis.

Heart attacks are very common in modern times

However, hydrogen-rich saline has been shown to reduce the size of myocardial infarction. Another group has found that hydrogen gas improves the recovery of left ventricular function after anoxia-reoxygenation (which means that reperfusion usually causes what is called reperfusion injury). Hydrogen reduced infarct size without altering haemodynamic parameters. Hydrogen gas also prevented left ventricular remodelling (the process of changing ventricular size, shape and function) after a myocardial infarction.

Subarachnoid haemorrhage is considered a life-threatening condition and can lead to brain cell death. Hydrogen is able to modify pathways that lead to death, particularly via the Akt/GSK3β pathway. This reduces apoptosis of neurons in the brain and improves outcome after subarachnoid haemorrhage.

Not only that, hydrogen can also act on the lungs and reduce cell death in lung injury. It induces anti-apoptotic genes. Thus, the anti-apoptotic protein Bcl 2 is upregulated and proteins that promote apoptosis, such as Bax, are downregulated.

Hydrogen has been shown to reduce apoptosis in the pancreas in acute pancreatitis, thus reducing the risk of developing diabetes mellitus.

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

Hydrogen can be ingested by inhaling the gas, inhaling a hydrogen-rich aerosol solution, injecting a hydrogen-rich saline solution, taking a hydrogen bath and drinking hydrogen dissolved in water. For daily ingestion, the most appropriate method is drinking hydrogen-enriched water or inhaling hydrogen gas produced by an electrolyser.

Although hydrogen is the most abundant chemical element in the universe, it has not yet been used in the therapeutic environment to treat disease. However, recent findings about this amazing gas have changed that. Hundreds of studies on hydrogen, so far mostly in animal models, suggest that it is also effective in humans for many diseases. It is safe to assume that we will see hydrogen in clinics in the near future. Because of its anti-apoptotic and anti-oxidant effects, it could also be used as an anti-ageing agent.

Sources

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 for 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 isogenic intestinal graft and improves recipient gastric function during transplantation. Transplantation, 2011. 92(9): p. 985-92.
Li, G.M., et al. Effects of treatment with hydrogen-rich saline 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 inhibits the inflammatory response in 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 from 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: pp. 121-124.

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.