Hydrogen sulfide in pharmacology and medicine – An update

Abstract

Hydrogen sulfide (H2S) is the endogenously produced gasotransmitter involved in the regulation of nervous system, cardiovascular functions, inflammatory response, gastrointestinal system and renal function. Together with nitric oxide and carbon monoxide, H2S belongs to a family of gasotransmitters. H2S is synthesized from L-cysteine and/or L-homocysteine by cystathionine β-synthase, cystathionine γ-lyase and cysteine aminotransferase together with 3-mercaptopyruvate sulfurtransferase. Significant progress has been made in recent years in our understanding of H2S biochemistry, signaling mechanisms and physiological role. H2S-mediated signaling may be accounted for not only by the intact compound but also by its oxidized form, polysulfides. The most important signaling mechanisms include reaction with protein thiol groups to form persulfides (protein S-sulfhydration), reaction with nitric oxide and related species such as nitrosothiols to form thionitrous acid (HSNO), nitrosopersulfide (SSNO(-)) and nitroxyl (HNO), as well as reaction with hemoproteins. H2S is enzymatically oxidized in mitochondria to thiosulfate and sulfate by specific enzymes, sulfide:quinone oxidoreductase, persulfide dioxygenase, rhodanese and sulfite oxidase. H2S donors have therapeutic potential for diseases such as arterial and pulmonary hypertension, atherosclerosis, ischemia-reperfusion injury, heart failure, peptic ulcer disease, acute and chronic inflammatory diseases, Parkinson's and Alzheimer's disease and erectile dysfunction. The group of currently available H2S donors includes inorganic sulfide salts, synthetic organic slow-releasing H2S donors, H2S-releasing non-steroidal antiinflammatory drugs, cysteine analogs, nucleoside phosphorothioates and plant-derived polysulfides contained in garlic. H2S is also regulated by many currently used drugs but the mechanism of these effects and their clinical implications are only started to be understood.

Effect of Novel Gasotransmitter hydrogen sulfide on renal fibrosis and connexins expression in diabetic rats

“…Gap junctions between histocytes participate jointly in multiple pathological processes, and they are also widely found in renal tissue. 6,7 It has been found that Cx43 is the most common Cx expressed in the kidney, while Cx45 and Cx40 expressions are also detected to some extent. For normal renal tissue cells, gap junction channel structures closely assembled on adjacent cellular membrane are responsible for information exchange, regulation of messangial cell growth and reproduction, renin secretion, renal blood flow and so on.…”

“…5,6 As the third important gaseous signal molecule in the body after NO and CO, H 2 S is involved in regulating renal function, neuron system, cardiovascular system, inflammatory response and gastrointestinal system. 7 By building diabetic rat model, this research was to observe renal fibrosis and change of Cxs expression in diabetic rats, as well as the influences of H 2 S on myocardial fibrosis and Cxs expression.…”

Endothelial Monocyteactivating Factor Ii Cancels Oxidative Stress, Сonstitutive Nos Uncoupling and Induced Violations of Cardiac Hemodynamics in Hypertension (Part Ii)

“…Продовжити цей ефект могли б, на наш погляд, речо вини, здатні одночасно пригнічувати активність аргінази (що забезпечувало б збереження L-аргініну для синтезу NO) й інгібувати деградацію гуанозинтрифосфату (що забез-печувало б збереження субстрату для синтезу важливого кофактора спряженого стану сNOS тетрагідробіоптерину (ВН 4 )) [24]. Можли ви ми довготривалими «ліквідато-рами» несп ряження сNOS можуть бути інгібітори інду цибельного синтезу H 2 S, на-приклад, про паргілгліцин [25].…”

Predictors of Kidney Damage in Patients with Metabolic Syndrome

“…Hydrogen sulfide (H2S) and nitrogen monoxide (NO) play a significant role in these processes [2,4,10]. Together with carbon monoxide (CO), they belong to the family of gasotransmitters which are involved in the regulation of the physiological functions of the cardiovascular, nervous and digestive systems [10].…”

“…Endothelial cells release H 2 S and NO in response to different stimuli including insulin, estradiol, acetylcholine, bradykinin, endothelium growth factor (EGF) [2][3][4]. In 2008, there was found that that H 2 S is released not only by smooth muscle cells of the vascular wall, but also by the endothelium [10].…”