Hydrogen sulphide (H2S) is a colourless gas with an odour of rotten eggs, long familiar to the students who worked in Chemistry Laboratories.
It is increasingly coming into light that, in fact, H2S can prevent cell damage in human from the noxious effect following myocardial infarction, brain stroke, traumatic brain injury, diabetes, atherosclerosis, Alzheimer’s disease and kidney injury etc.. This gas, in minute quantities, which is yet to be quantified, may actually protect mitochondria the power house of body.
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| Photo Credit: Mail Online Health |
It is produced in the human gut, mostly in colon by fermentation of food from bacterial action. Cystathioneine-lyase (CSE) and cystathionine-synthase are the two enzymes that regulate H2S levels in mammals (including humans).
CSE is found in the liver and vascular smooth muscle cells, but cystathioinine-synthase produces H2S in the brain.
Garlic can be transformed into H2S by enzymatic action in the body, so that some of its claimed medicinal properties can be traced to H2S.It has been seen to be an important mediator of gastrointestinal (GI) mucosal defence and contributes significantly to repair of damage and resolution of inflammation. Synthesis of H2S increases markedly after mucosal injury, and inhibition of H2S in such circumstances leads to delayed healing and exacerbated inflammation.
The beneficial effects of H2S may be attributable to its ability to elevate mucosal blood flow, prevent leukocyte-endothelial adhesion, reduce oxidative stress, and stimulate angiogenesis.
Thus novel H2S -based therapies have been shown to be effective anti-inflammatories that can promote the resolution of inflammation and accelerate the healing of GI ulcers. Encouraging results have already been seen experimentally with a mesalamine derivative and with H2S -releasing derivatives of non-steroidal anti-inflammatory drugs.
Researchers at Johns Hopkins University, in Maryland, found that the H2S gas is produced in the cells lining blood vessels by CSE that relaxes the blood vessels, may have a role in regulating blood pressure.
In neurotoxin-induced Parkinson’s disease animal models, it has been seen that sodium hydrogen sulphate (NaHS), an H2S donor, reversed dopaminergic neuron loss via its anti-oxidant, anti-inflammatory and anti-apoptotic effects.
It has been found that the characteristic memory deficiency in Alzheimer’s disease (AD) may be related to reduced H2S and administration of NaHS could provide a therapeutic approach for AD. Sufficient evidence has accumulated in support of H2S acting as a signalling molecule in the mammalian Central Nervous System (CNS).
Its beneficial effect in Alzheimer’s disease in animal models has also been substantiated. It has been seen that NaHS inhibited formation of amyloid β , which is a major component of the neuritic plaques by down-regulation of β-amyloid precursor protein (APP) expression and suppression of the activity of β-secretase, a β-site APP cleaving enzyme 1 (BACE1).
Abnormal accumulation of tau protein, a neuronal microtubule-associated protein that causes paired helical fragments (PHF) in Alzheimer’s disease is inhibited by NaHS through hyperphosphorylation, polymerization and aggregation.
Hydrogen sulfide has recently been found decreased in chronic kidney disease. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin.
At the same time, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased.
In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and down-regulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc.
Further, the hydrogen sulphide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-β1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulphide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease. Experiments with mice have shown that H2S can reduce their ability to metabolize oxygen, reducing their heart rate and breathing rate, lowering their body temperature, and creating a state of deep hibernation. By flushing with air, the mice can be restored to normal without apparent behavioural effects.
The possibility of using H2S in heart surgery or treating badly injured soldiers is being studied. By studying roundworms (C. elegans) it has been shown that 50 parts per million of H2S can extend their lives by 70 percent. This "fountain of youth" phenomenon seems to be connected to the gene SIR-2, which had previously been related to life span regulation.
These preliminary findings are very exciting and may lead to medical advances. H2S appears to be another example of a "gasotransmitter" such as the hormone NO. Researchers speculates that H2S may be involved in the hibernation of certain animals.
Now researchers have come up with a new compound named AP39 to assist the body in producing just the right amount of hydrogen sulphide.
They believe that it will help prevent or reverse mitochondrial damage, which is a key strategy in treating conditions such as stroke, heart failure, diabetes, arthritis, dementia and ageing.
The past few years demonstrated its role in many biological systems and it is becoming increasingly clear that H2S is likely to join nitric oxide (NO) and carbon monoxide (CO) as a major player in mammalian a cardioprotectant for treating ischaemic heart diseases and heart failure.
H2S treatment represents a novel therapeutic strategy to prevent acute lung injury induced by high tidal volume (HVT) ventilation. Moreover, it is pivotally involved in the control of important functions in the central nervous system (CNS).
H2S facilitates the induction of hippocampal long-term potentiation by enhancing the activity of N-methyl D, L-aspartate (NMDA) receptors. H2S induces Ca2+influx in astrocytes that propagates to the surrounding astrocytes as Ca2+ waves.
In stroke, H2S appears to act as a mediator of ischemic injuries and thus inhibition of its production has been suggested to be a potential treatment approach in stroke therapy.
Cerebral oedema has been reported to be one of the major factors leading to the high mortality and morbidity associated with patients with traumatic brain injury (TBI).
A recent study interestingly showed that H2S at a low concentration significantly attenuated the injury in a mild focal cerebral ischemia rat model.
It was observed that low concentration of H2S is neuro-protective, whereas higher concentrations of H2S have been shown to magnify cerebral damage.
H2S may serve as a neuroprotectant to treat TBI-induced brain injury via anti-apoptosis and suppression of excessive activation of autophagy therefore has potential clinical therapeutic value for treatment of TBI.
This field is still in its infancy and much will be learnt in the near future about the central roles play by H2S in health and disease
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