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
Related Articles
- EP ID EP203459
- DOI -
- Views 75
- Downloads 0
AGE DYNAMICS OF THE GALLBLADDER AND EXTRAHEPATIC BILIAR DUCTS LINEAR PARAMETERS IN DIFFERENT GENDERS PERSONS.
The increase in the pathology of the hepatobiliary system in the structure of somatic diseases induces the search for morphological features of the structures of this system, in order to prevent the development of pathol...
THE RIGHT TO LIVE. THE RIGHT TO DIE
The author – doctor and the high education teacher is trying to answer the painful question: Is euthanasia for incurable patients, crippled, mentally handicapped, unborn children with identifi ed prenatal defects in deve...
EVALUATION OF DEFINITION ” HEALTH” AND ”DISEASE”
На нашу думку визначення «здоров’я» згідно рекомендації ВООЗ є неправомірним. «Здоров’я» в нашому розумінні може бути як процес вдосконалення всіх складових: біологічної, моральної, соціальної, духовної сторін, при цьому...
CRYSTAL STRUCTURE OF THE ARSENIDE HfNiAs
Crystal structure of the earlier known ternary arsenide with equimolar composition HfNiAs was refined by X-ray powder diffraction method and atomic positional parameters were determined: space group Pnma, TiNiSi-type str...
ASSESSMENT OF LEAD AND CADMIUM CONTENT IN THE BLOOD OF PREGNANT AND NON-PREGNANT WOMEN
The reproductive health care is a priority prob- lem due to the unhealthy environment. In this regard, a particular attention should be paid to the research of the heavy metal content in wom- en organisms, which can be...