EVALUATION OF POTENTIAL GASTROPROTECTIVE EFFECTS OF H2S, CO AND NO ON EXPERIMENTAL ULCER MODELS IN RATS

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Background: Gastric mucosal damage induced by ethanol, stress and indomethacin is a serious problem. NO, H2S and CO are gaseous autacoids and they are used in several areas of real-life for medical purposes. It is known that NO has protective effects on gastric mucosa. Recently some studies indicated that H2S and CO also have gastroprotective effects. This study was planned to evaluate and compared the protective effects of these gaseous autacoids on ethanol, indomethacin and stress-induced gastric ulcer models.

Methods:The putative gastroprotective effects of three different autacoid precursors, L-arginine (100 mg/kg, i.p.) for NO, NaHS (5 mg/kg, i.g) for H2S, CORM-2 (Carbonmonoxide eleasing molecule-2=tricarbonyldichlororuthenium (II) dimer) (5 mg/kg, i.g) for CO were examined on three different gastric ulcer models (ethanol 1ml 96% i.g.), indomethacin (40 mg/kg i.g.) and stress (cold+immobility). The results were evaluated by measuring ulcer index, gastric mucus secretion, free and total acidity, the levels of MDA GSH, non-protein sulfhydryl groups (NP-SH), TNF alpha;, PGE2, COX-1, COX-2.

Results: It was found that CORM-2 and NaHS showed gastroprotective activity against ethanol-induced ulcers. L-arginine was also gastroprotective against stress-induced ulcers. The significant induction of mucus secretion and reduction of MDA levels were observed in the ethanol group by CORM-2 and NaHS. The inhibition of acidity and increase of COX-1 levels were determined in the stress group by L-arginine .Although significant and increased levels of mucin were noticed by indomethacin, increases of acidity and MDA, inhibition of COX-2 and PGE2 stimulated significantly gastric ulcers. None of these agents had gastroprotective activity against indomethacin-induced ulcers. L-arginine and CORM-2 stimulated COX-2 and L-arginine, CORM-2 and NaHS increased PGE2 levels and acidity. But these effects were not sufficient to protect the indomethacin-induced gastric ulcers. We could not observe any effect of CO, H2S and NO on increased levels of total acidity induced by ethanol, indomethacin and stress.

Conclusions:It seems that CO and H2S might have gastroprotective effects against ethanol-induced ulcers and NO against stress-induced ulcers. This study may contribute to the development of new antiulcerogenic agents and the possible mechanisms underlied in these activities.

This study is supported by ESOGU-Scientific Research Project No: 201611A234