INFLUENCE OF HYDROGEN SULFIDE-RELEASING ASPIRIN ON M UCOSAL INTEGRITY OF ESOPHAGEAL AND GASTRIC MUCOSA
Journal Title: Праці Наукового товариства ім. Шевченка - Year 2015, Vol 43, Issue 2
Abstract
Introduction. Aspirin is one o f the widely prescribed antiplatelet and anti-inflammatory drugs and last data expanded its role into complex biological processes such as cancerogenesis, despite the fact that its effects for peptic ulcer or gastrointestinal (GI) bleeding, which can develop even in an achlorhydric environment, are well known. Recent extensive research o f activities o f hydrogen sulfide (H2S) has proven that the addition of H2S-releasing moiety to the classical nonstreroid anti-inflammatory drugs (NSAID) results in GI cytoprotective activity. The aim o f this study was to evaluate dose-dependent effects o f a novel NSAID-H2S compound - ATB 340 (Antibe Therapeutics Inc), hydrogen sulfide-releasing derivative of aspirin, 4-(5-thioxo-5H-dithiol-3-yl) phenyl 2-acetoxybenzoate (HS'-aspirin) vs classical aspirin (ASA) on esophageal and gastric mucosal integrity. Methods: A blind, randomized study on rats treated with single administration of the vehicle (control), ASA (in the doses 3.0; 10.0; 30.0; 100.0 mg/kg) and ATB-340 (in the doses 5.25; 17.5; 52.5; 175.0 mg/kg) with a vehicle (1.0 ml o f 1% carboxymethylcellulose) and 7-days administration o f ASA (3.0 and 10.0 mg/kg) and ATB-340 (5.25 and 17.5 mg/kg) was done. The damage o f the esophageal mucosa (EM) and gastric mucosa (GM) was estimated by macro- and microhistological analyses using damage scores; endothelial leukocyte adherence was examined using intravital microscope before and after ASA and ATB-340 administration. Results: Treatment by ATB-340 resulted in cyprotective effect and lower grade o f EM and GM lesions with damage score being twice less than ASA. Effective cytoprotective and an anti-inflammatory dose o f ATB-340 was 17.5 mg/kg during single or 7-day administration. Treatment by ATB-340 (in the dose o f 17.5 mg/kg) vs ASA exerted a strong anti-inflammatory effect by decreasing leukocyte adherence 4 times vs ASA and showing vasoprotective effect. Conclusion: H.S-aspirin exerts strong cytoprotective and anti-inflammatory dose- depended effects on EM and GM. An effective anti-inflammatory and vasoprotective dose of H.S-aspirin with low risk o f damage of GI mucosal barrier is 17.5 mg/kg.
Authors and Affiliations
John WALLACE1, Marcelo N. MUSCARA, Oksana Zayachkivska, Irena PSHYK-TITKO, Yaroslav Pavlovsky, Nazar Bula, Elene Gavriluk
Keywords
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