ACTION OF HYDROGEN SULFIDE RELEASING 2-MERCAPTOACRYLIC ACID-BASED DERIVATIVE ON NITRIC OXIDE METABOLISM AND OXIDATIVE STRESS IN SMALL INTESTINE OF RATS WITH MEDICATION-INDUCED ENTEROPATHY
Journal Title: Праці Наукового товариства ім. Шевченка - Year 2017, Vol 49, Issue
Abstract
Small intestinal injury is one of the most commonly appeared pathologies resulting in use of medications such as: nonsteroidal anti-inflammatory drugs (NSAIDs), anti-tumor drugs and inhibitors of angiotensin-converting enzyme (ACE). Taking into consideration the fact that these drugs are widely used for the treatment of various serious diseases, the search of new drugs without any side effects is an important medical and pharmaceutical problem. A new approach in this sphere may be demonstrated by novel sulfur-containing compounds based on mercaptoacrylic acids and thiazolidinones as their synthetic precursors which possessing a dual COX/lipoxygenase (LOX) inhibitory action. The purpose of this study is to evaluate the action of a novel 2-mercaptoacrylic acid-based, possessing dual COX/LOX inhibitory action and able to release H2S on parameters of NO-synthase system and oxidative stress at the background of drug-induced enteropathy. The structure of this study and the experimental procedures performed on the animals were approved by the Ethical Committee of Lviv National Medical University. Three types of medications were used to induce enteropathy: indomethacin, a NSAID (35 mg/kg); metothrexate, an anti-tumor drug (10 mg/kg); enalaprile, an ACE inhibitor (2 mg/kg/day). 2-[(4-chlor-phenyl-carbamoyl)-methyl]-3(3,5-Di-tert-butyl-4-hydroxyphenyl)-acrylic acid (2C3DHTA) was introduced on the background of medication-induced entepopathy (10 mg/kg/day). In the mucosa of small intestine were determined: malonic dialdehyde (MDA) concentration, activity of mieloperoxydase (MPO), superoxide dismutase (SOD), catalase, NO-synthases (NOS). Administration of indomethacin induced the development of ulcerative lesion of small intes-tine manifested by erosions and haemorrhages, localised mainly in its distal part. Neither metothrexate nor enalapril caused any visual changes of small intestine surface. It should be pointed out that metothrexate-treated animals were suffering from severe enterotoxicosis manifested by diarrhoea and vomiting. In spite of different mechanisms of their action upon metabolic processes in small intestine, all used medications (indomethacin, metothrex- ate and enelaprile) caused serious changes of NO-synthase system parameters. Administration of indomethacin and metothrexate caused a rise in iNOS activity. ACE-inhibitor decreased cNOS activity. 2C3DHTA demonstrated a cytoprotective effect: it returned iNOS activity to its control level and increased cNOS activity. Enterotoxic action of studied medication was accompanied by the development of oxidative stress manifested by rise of MDA concentration, activity of MPO was increased. 2C3DHTA reduced MPO activity and manifestations of oxidative stress. Effects of 2C3DHTA on one hand can be explained by action of H2S, released from this compound in gastrointestinal system, on the other hand by the dual inhibition of pro-inflammatory enzymes COX and LOX. Thus in our study we showed, that H2S released from compound 2C3DHTA was involved in mechanisms cytoprotection in small intestine.
Authors and Affiliations
I. Fomenko, Yu. Sklyarova, N. Denysenko, R. Lesyk
METFORMIN THERAPY FOR PATIENTS WITH METABOLIC SYNDROM ASSOCIATED WITH CHRONIC PANCREATITIS
Nowadays the problem of average increasing number of cases of peoplesuffering from inveterate non communicable diseases is discussed much. Metabolic syndrome (MS) has already reached proportions of non communicable epide...
ЗДОБУТКИ І ПЕРСПЕКТИВИ УКРАЇНСЬКОЇ АСОЦІАЦІЇ ЛІКАРІВ-КАТОЛИКІВ У ЛЬВОВІ (ПРИСВЯЧЕНА 15-РІЧЧЮ ДІЯЛЬНОСТІ) (доповідь Президента асоціації)
Сьогодні ми зібралися на академії, присвяче- ній п’ятнадцятиріччю діяльності Асоціації лікарів- католиків в Україні, зокрема у Львові. Католиць- ка Церква навчає, що «життя і фізичне здоров’я є цінним добром, даним Богом...
REJUVENATION OF A BODY: DISCOVERY LEADING TO THE DRASTIC CHANGES OF GERONTOLOGY OPPORTUNITIES (REVIEW OF PERSONAL RESEARCHES)
Only the one who clearly defi nes the meaning of words can discover the truth The author has discovered thrombin-plasmin system (TPS) and two processes performed by its subsystems being fundamentally opposed, internally...
HYDROGEN SULFIDE SYSTEM ATTENUATES INJURY BY HYPERGLYCEMIA AND STRESS: ROLE OF MESENTERIC ADIPOCYTES IN AGED ANIMALS
The mesentery is one of recently described separate organs which functions and its ability to protect injury are still unclear. Adipocytes are a part of mesentery (MAC), however, it is a little known about their age-rela...
LIFE PHENOM ENA AND THEIR METHODS OF INVESTIGATION
The inaugural lecture of Dr. Adolf Beck, Professor of Physiology Department of University of Lwow given at the 29th of October 1895* The first year of doctor education in our local department gives you a possibility to s...