Gaseous Mediators Nitric Oxide and Hydrogen Sulfide in the Mechanism of Gastrointestinal Integrity, Protection and Ulcer Healing

Abstract

Nitric oxide (NO) and hydrogen sulfide (H2S) are known as biological messengers; they play an important role in human organism and contribute to many physiological and pathophysiological processes. NO is produced from L-arginine by constitutive NO synthase (NOS) and inducible NOS enzymatic pathways. This gaseous mediator inhibits platelet aggregation, leukocyte adhesion and contributes to the vessel homeostasis. NO is known as a vasodilatory molecule involved in control of the gastric blood flow (GBF) and the maintenance of gastric mucosal barrier integrity in either healthy gastric mucosa or that damaged by strong irritants. Biosynthesis of H2S in mammals depends upon two enzymes cystathionine-β-synthase and cystathionine γ-lyase. This gaseous mediator, similarly to NO and carbon monoxide, is involved in neuromodulation, vascular contractility and anti-inflammatory activities. For decades, H2S has been known to inhibit cytochrome c oxidase and reduce cell energy production. Nowadays it is generally considered to act through vascular smooth muscle ATP-dependent K + channels, interacting with intracellular transcription factors and promote sulfhydration of protein cysteine moieties within the cell, but the mechanism of potential gastroprotective and ulcer healing properties of H2S has not been fully explained. The aim of this review is to compare current results of the studies concerning the role of H2S and NO in gastric mucosa protection and outline areas that may pose new opportunities for further development of novel therapeutic targets.

Possible contribution of nitric oxide and prostaglandin in the protective effect of angiotensin (1-7) against stress induced gastric ulceration in adult male albino rats

“…L-NNA pre-treatment inhibited the restoration of stress-induced decrease in NO level by Ang-(1-7) pre-treatment. Since NO is the endothelium derived relaxing factor, reduction of its level might contribute to reduced mucosal blood fl ow by the vasoconstriction response with a subsequent gastric damage (29).…”

Nitric oxide, afferent sensory nerves, and antioxidative enzymes in the mechanism of protection mediated by tricarbonyldichlororuthenium(II) dimer and sodium hydrosulfide against aspirin-induced gastric damage

“…The gaseous mediators hydrogen sulfide (H 2 S), carbon monoxide (CO), and nitric oxide (NO) were reported to afford gastroprotection against injury induced by noxious agents but the mechanism of this beneficial action of these molecules has not been fully elucidated [5][6][7][8][9][10]. All three mediators have been shown to take part in regulation of physiological processes in the gastrointestinal tract and other systems [11][12][13].…”

Preventive and therapeutic strategies of pharmaco-correction gastropathy induced by nonsteroidal anti-inflammatory drugs

“…Мишенью газотрансмиттеров служит покровный эпителий же-лудка и кишечника, в котором под влиянием H 2 S и NO установлена активация продукции слизи и бикарбо-натов [34,51]. Показано стимулирующее действие газов-медиаторов на пролиферацию недифферен-цированных клеток, что обеспечивает репарацию язвенных дефектов [22,34]. Важным элементом протекторного действия газвысвобождающих пре-паратов на ЖКТ являются оптимизация состава флоры и восстановление взаимоотношений между макро-и микроорганизмом [37].…”

“…Важным элементом протекторного действия газвысвобождающих пре-паратов на ЖКТ являются оптимизация состава флоры и восстановление взаимоотношений между макро-и микроорганизмом [37]. Следует отметить, что газообразные медиаторы принимают участие в регуляции процессов апоптоза и пролиферации клеток СО ЖКТ [34].…”

“…Все эти эффекты способствуют повышению защиты слизистой обо-лочки ЖКТ и, следовательно, обеспечивают сниже-ние тяжести повреждения слизистой при действии НПВП. Кроме того, эндогенный NO играет важную роль в заживления язв [22,34]. Эти факты легли в основу разработки NO-высвобождающих НПВП (CINODs -сyclooxygenase-inhibiting nitric oxide donors): NO-ас пи рин, NO-диклофенак, NO-напро-ксен, NO-флу бипрофен, NO-кетопрофен, NO-сулин-дак, NO-ибупрофен, NO-индометацин и др.…”