Ukr.Biochem.J. 2016; Том 88, спецвипуск, c. 99-104

The influence of novel 4-thiazolidinone derivaties in cytoprotective mechanisms of small intestine under nsaid-induced damage

19.07.2016   Без категорії   No comments

I. I. Ilkiv, R. B. Lesyk, O. Ya. Sklyarov

Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
e-mail: ira9ilkiv@gmail.com

The aim of investigation was to compare the action of novel 4-thiazolidinone derivaties (compounds Les-5054 and Les-5055) toward parameters of nitroso-oxidative processes in mucous membrane of small intestine (MMSI) in rats on the background of indomethacin induced injury. The activity of nitric oxide synthases, myelopeoxidase, content of NO, and parameters of lipoperoxidation processes were measured in MMSI and the level of H2S and L-arginine in blood serum. Administration of indomethacin caused significant destructive damages in distal part of small intestine and increase in activity of inducible nitric oxide synthase (iNOS) and intensity of lipoperoxidation  processes in comparison to control were observed. Also indomethacin injection was accompanied by decrease of H2S and L-arginine level in blood serum. Administration of 4-thiazolidinone derivaties on the background of indomethacin induced injury reduce the activity of iNOS, myeloperoxidase, intensity of lipid peroxidation and increase generation of H2S, that may be linked with the structure of this compounds. However compound Les-5054 showed more significant cytoprotective effect and antioxidant properties than compound Les-5055. Thus, the novel 4-thiazolidinone derivaties led to reduce of nitroso-oxidative processes caused by administration of NSAIDs.

Ключові слова: , , ,

Посилання:

  1. Magierowski M, Magierowska K, Kwiecien S, Brzozowski T. Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing. Molecules. 2015 May 19;20(5):9099-123. Review. PubMed, CrossRef
  2. Geng B, Chang L, Pan C, Qi Y, Zhao J, Pang Y, Du J, Tang C. Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochem Biophys Res Commun. 2004 Jun 4;318(3):756-63. PubMed
  3. Fomenko I, Sklyarov A, Bondarchuk T, Biletska L, Panasyuk N, Wallace JL. Effects of conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with stress-induced and epinephrine-induced gastric damage. Stress. 2014 Dec;17(6):528-37. PubMed, CrossRef
  4. Gu X, Zhu YZ. Therapeutic applications of organosulfur compounds as novel hydrogen sulfide donors and/or mediators. Expert Rev Clin Pharmacol. 2011 Jan;4(1):123-33. Review. PubMed, CrossRef
  5. Fiorucci S, Antonelli E, Distrutti E, Rizzo G, Mencarelli A, Orlandi S, Zanardo R, Renga B, Sante M, Morelli A, Cirino G, Wallace JL. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs. Gastroenterol. 2005; 129(4): 1210-1224.
  6. Geronikaki AA, Lagunin AA, Hadjipavlou-Litina DI, Eleftheriou PT, Filimonov DA, Poroikov VV, Alam I, Saxena AK. Computer-aided discovery of anti-inflammatory thiazolidinones with dual cyclooxygenase/lipoxygenase inhibition. J Med Chem. 2008 Mar 27;51(6):1601-9. PubMed, CrossRef
  7. Lozynskyi AV, Kaminskyy DV, Roman­chyshyn KB, Semenciv NG, Ogurtsov VV, Nektegayev IO, Lesyk RB. Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles. Biopolym Cell. 2015; 31(2): 131-137.  CrossRef
  8. Lesyk RB, Zimenkovsky BS. 4-Thiazolidones: centenarian history, current status and perspectives for modern organic and medicinal chemistry. Curr Org Chem. 2004; 8(16): 1547-1577. CrossRef
  9. Yarushkina NI, Bagaeva TR, Filaretova LP. Somatic pain sensitivity under indometacin induced gastric and small intestinal injury in rats. Ross Fiziol Zh Im I M Sechenova. 2014 Jan;100(1):73-85. Russian. PubMed
  10. Sharath Kumar KS, Hanumappa A, Vetrivel M, Hegde M, Girish YR, Byregowda TR, Rao S, Raghavan SC, Rangappa KS. Antiproliferative and tumor inhibitory studies of 2,3 disubstituted 4-thiazolidinone derivatives. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3616-20.  PubMed, CrossRef
  11. Sumbajev VV, Yasinskaya IM. The influence of DDT on nitric oxide synthase activity in liver, lungs and brain of rats. Modern Probl Toxycol. 2000; 3: 3-7. (In Russian).
  12. Alejnikova TL, Rubtsova GV, Pavlova NA.  Manuals for practical lessons in biochemistry. M.: Medicine, 2000. 128 p. (In Russian).
  13. Olkhovskiy OS, Zaichko N. Influence propargyl glycine and sodium content of hydrogen and H2S-indices of antioxidant system in the myocardium of rats of different ages. Med Chem. 2013; 15(4): 10-15. (In Ukrainian).
  14. Timirbulatov RA, Seleznev EI. Method for increasing the intensity of free radical oxidation of lipid-containing components of the blood and its diagnostic significance. Lab Delo. 1981;(4):209-11. Russian. PubMed
  15. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982 Mar;78(3):206-9. PubMed, CrossRef
  16. Csóvári S, Andyal T, Strenger J. Determination of the antioxidant properties of the blood and their diagnostic significance in the elderly. Lab Delo. 1991;(10):9-13. Russian. PubMed
  17. Koroliuk MA, Ivanova LI, Mayorova IG, Tokarev VE. A method of determining catalase activity. Lab Delo. 1988;(1):16-9. Russian. PubMed
  18. Sklyarov AY, Lesyk RB, Panasyuk NB, Fomenko IS, Havrylyuk DY. Comparison of dual acting drugs and conventional NSAIDs towards parameters of NO-synthase system and oxidative stress in mucosal membrane of large intestine of rats with experimental ulcerative colitis. Biopolym Cell. 2011; 27(2): 147-153.  CrossRef
  19. Pálinkás Z, Furtmüller PG, Nagy A, Jako­pitsch C, Pirker KF, Magierowski M, Jasnos K, Wallace JL, Obinger C, Nagy P. Interactions of hydrogen sulfide with myeloperoxidase. Br J Pharmacol. 2015; 172(6): 1516-1532. CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.