Vliv nesteroidních protizánětlivých léčiv s různými mechanismy účinku na tělesnou teplotu a dráhu cyklooxygenázy kaskády kyseliny arachidonové na modelu akutního celkového ochlazení (vzduchová hypotermie) u potkanů

Stáhnout PDF English version

Autoři: Sergiy Shtrygol; Olga Tovchiga; Olesia Kudina; Olga Koiro; Tetiana Yudkevich; Tetiana Gorbach
Vyšlo v časopise: Čes. slov. Farm., 2022; 71, 214-223
Kategorie: Původní práce
doi: https://doi.org/https://doi.org/10.5817/CSF2022-5-214

Souhrn

NSAID jsou slibné látky pro prevenci poškození chladem (frigoprotektiva). Vliv profylaktického podávání neselektivního inhibitoru COX diklofenaku sodného (7 mg/kg) a vysoce selektivního inhibitoru COX-2 etorikoxibu (5 mg/kg) na biomarkery cyklooxygenázové dráhy byl studován na modelu akutního celkového ochlazení (vzduchová hypotermie při –18 °C po dobu 2 hodin). Diklofenak zcela zabránil poklesu tělesné teploty a předčil etorikoxib. V játrech potkanů byl bezprostředně po expozici chladu mírně zvýšen obsah COX-1, velmi výrazně obsah COX-2, snížena hladina PGE2 a zvýšeny hladiny PGF2α a zejména PGI2 a TXB2. V krevním séru byla hladina COX-1 snížena a změny hladin COX-2 a prostaglandinů byly podobné jako v játrech. Diklofenak působil mírně směrem k normalizaci obou izoforem COX v játrech, mírně zvyšoval obsah PGE2 a snižoval – PGF2α a TXB2, aniž by měnil hladinu PGI2. V séru diklofenak snížil hladinu COX-1 na podnormální hodnoty a jeho účinek na ostatní biomarkery byl podobný jako v játrech, s výjimkou mírného snížení PGI2. Diklofenak byl tedy horší než etorikoxib, který normalizoval COX-1, COX-2, PGE2, PGI2 v játrech, snížil obsah PGF2α a TXB2 v játrech na podnormální hodnoty, zatímco v krevním séru snížil COX-1, COX-2, PGE2 na podnormální hodnoty, normalizoval PGF2α a PGI2, významně snížil TXB2. Opačný stupeň intenzity vlivu diklofenaku a etorikoxibu na cyklooxygenázovou dráhu a tělesnou teplotu svědčí o disociaci protizánětlivé a frigoprotektivní aktivity. Inhibice oxidačního stresu není pro frigoprotektivní aktivitu NSAID rozhodující, protože diklofenak i přes slabší vliv na obsah 8-isoprostanu v játrech stále vykazuje maximální frigoprotektivní aktivitu.

Klíčová slova:

tělesná teplota – prevence poškození chladem – cyklooxygenáza – prostaglandiny – diklofenak sodná sůl – etorikoxib – frigoprotektivní aktivita

Zdroje

1. Biem J., Koehncke N., Classen D., Dosman J. Out of the cold: management of hypothermia and frostbite. Canadian Medical Association Journal 2003; 168(3), 305– 311.

2. Centers for Disease Control and Prevention. QuickStats: Death Rates Attributed to Excessive Cold or Hypothermia Among Persons Aged ≥ 15 Years, by Urban-Rural Status and Age Group – National Vital Statistics System, United States, 2019. MMWR Morb Mortal Wkly Rep. 2021; 70(7), 258. https://www.cdc.gov/mmwr/volumes/70/wr/ mm7007a6.htm (01.07.22).

3. Cold Weather Injuries, Active and Reserve Components, US Armed Forces, July 2014–June 2019. https://www. health.mil/News/Articles/2019/11/01/Cold-Weather- Injuries (01.07.22).

4. Fudge J. Exercise in the Cold: Preventing and Managing Hypothermia and Frostbite Injury. Sports Health 2016; 8(2), 133–139. doi:10.1177/1941738116630542.

5. McIntosh S. E, Opacic M., Freer L., Grissom C. K., Auerbach P. S, Rodway G. W., Cochran A., Giesbrecht G. G., McDevitt M., Imray C. H., Johnson E. L., Dow J., Hackett P. H. Wilderness Medical Society practice guidelines for the prevention and treatment of frostbite: 2014 update. Wilderness Environ Med. 2014; 25(4), 43– 54. doi:10.1016/j.wem.2014.09.001.

6. Sachs C., Lehnhardt M., Daigeler A. The Triaging and Treatment of Cold-Induced Injuries. Deutsches Arzteblatt International 2015; 112, 741–748.

7. Fosslien E. Review: Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs. Annals of Clinical & Laboratory Science 2005; 4(35), 347–385.

8. Polderman K. H. Mechanisms of action, physiological effects, and complications of hypothermia. Critical Care Medicine 2009; 37, 186–202. doi:10.1097/CCM. 0b013e3181aa5241.

9. Romanovsky A. A, Garami A. Prostaglandin riddles in energy metabolism: E is for excess, D is for depletion. Focus on “Food deprivation alters thermoregulatory responses to lipopolysaccharide by enhancing cryogenic inflammatory signaling via prostaglandin D2”. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2010; 298(6), 1509– 1511. doi:10.1152/ajpregu.00253.2010.

10. Ueno R., Narumiya S., Ogorochi T., Nakayama T., Ishikawa Y., Hayaishi O. Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide. Proc. Natl. Acad. Sci. USA 1982; 79(19), 6093–6097. doi:10.1073/pnas.79.19.6093.

11. Imray C., Grieve A., Dhillon S. Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgraduate Medical Journal 2009; 85, 481–488.

12. Kapelka I. G., Shtrygol’ S. Yu. The comparative research of frigoprotective properties of nonsteroidalantiinflammatory drugs оn the model of acute general cooling. [Article in Ukrainian]. Pharmacol. Drug Toxicol. 2019; 13(5), 338–343. doi: 10.33250.13.05.338.

13. Kapelka I. G., Shtrygol’ S. Yu., Lesyk R. B., Lozynskyi A. V., Khomyak S. V., Novikov V. P. The comparative research of arachidonic acid cascade inhibitors forfrigoprotective activity. [Article in Ukrainian]. Pharmacol. Drug Toxicol. 2020; 14(2), 122–128. doi:10.33250/14.02.122.

14. Kapelka I., Shtrygol’ S., Koiro O., Merzlikin S., Kudina O., Yudkevich T. Effect of arachidonic acid cascade inhibitors on body temperature and cognitive functions in rats in the Morris water maze after acute cold injury. Pharmazie 2021; 76(7), 313–316. doi:10.1691/ ph.2021.1571.

15. Shtrygol’ S., Koiro O., Kudina O., Tovchiga O., Yudkevich T., Oklei D. The influence of non-steroidal anti-inflammatory drugs with different mechanisms of action on the course of stress reaction, the functional state of kidneys, liver, and heart on the model of acute general cooling ScienceRise: Pharmaceutical Science 2022; 2(36), 46–55. doi:10.15587/2519-4852.2022.255797

16. Kapelka I. G., Shtrygol’ S. Yu. The characteristics of the anti-inflammatory action of sodium diclofenac in cold and normal environment. [Article in Ukrainian]. News of Pharmacy 2020; 2, 106–112. doi:10.24959/nphj.20.37

17. Thomas G., Sousa P. S. Early inflammatory response to carrageenan in the pleural cavity and paw of rats with altered body temperature. The Journal of Pharmacy and Pharmacology 1986; 38. 936–938. doi:10.1111/j.2042-7158. 1986.tb03390.x

18. Bondarev Ye. V., Shtrygol’ S. Yu, Drogovoz S. M., Shchokina K. G. Cold injury: preclinical development of medicinal preparations with frigoprotective properties. [Document in Ukrainian]. Guidelines of the Ministry of Health of Ukraine, Kharkiv: National Pharmaceutical University 2018.

19. Ren J, Liu C, Zhao D, Fu J. The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress. Environ Sci. Pollut. Res. Int. 2018; 25(21), 21011–21023.

20. McIntosh S. E., Freer L., Grissom C. K., Auerbach P. S., Rodway G. W., Cochran A., Giesbrecht G. G., McDevitt M., Imray C. H., Johnson E. L., Pandey P., Dow J., Hackett P. H. Wilderness medical society clinical practice guidelines for the prevention and treatment of frostbite: 2019 Update. Wilderness Environ Med. 2019; 30(4S), 19– 32. doi:10.1016/j.wem.2019.05.002.

21. Poole A., Gauthier J. Treatment of severe frostbite with iloprost in northern Canada. Canadian Medical Association Journal 2016; 188(17–18), 1255–1258. doi:10.1503/cmaj.151252.

22. Sachs C., Lehnhardt M., Daigeler A., Goertz O. The triaging and treatment of cold-induced injuries. Dtsch Arztebl Int. 2015; 112(44), 741–747.

23. Oliveira M. S., Furian A. F., Royes L. F., Fighera M. R., Fiorenza N. G., Castelli M., Machado P., Bohrer D., Veiga M., Ferreira J., Cavalheiro E. A., Mello C. F. Cyclooxygenase-2/PGE2 pathway facilitates pentylenetetrazol-induced seizures. Epilepsy Research 2008; 79(1), 14–21. https://doi.org/10.1016/j.eplepsyres. 2007.12.008

24. Brune K, Patrignani P. New insights into the use of currently available non-steroidal anti-inflammatory drugs. J. Pain Res. 2015; 8, 105–118.

25. Patrignani P., Tacconelli S., Bruno A., Sostres C., Lanas A. Managing the adverse effects of non-steroidal antiinflammatory drugs. Expert Rev. Clin. Pharmacol. 2011; 4(5), 605–621.

26. Van Hecken A., Schwartz J. I., Depré M., De Lepeleire I., Dallob A., Tanaka W., Wynants K., Buntinx A., Arnout J., Wong P. H., Ebel D. L., Gertz B. J., De Schepper P. J. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J. Clin. Pharmacol. 2000; 40(10), 1109–1120.

27. Ehrlich H. P., Needle A. L., Rajaratnam J., White M. E., White B. S. The role of prostacyclin and thromboxane in rat burn and freeze injuries. Exp. Mol. Pathol. 1983; 38(3), 357–367.

28. Ehrlich H. P. Promotion of vascular patency in dermal burns with ibuprofen. Am J. Med. 1984; 77(1A), 107–113.

29. Gulati S. M., Kapur B. M., Talwar J. R. Oxyphenbutazone (anti-inflammatory agent) in the management of cold injury. Angiology 1969; 20(7), 367–373.

30. Johnson J. M., Minson C. T., Kellogg Jr D. L. Cutaneous vasodilator and vasoconstrictor mechanisms in temperature regulation. Compr. Physiol. 2014; 4(1), 33– 89.

31. Holowatz L. A., Jennings J. D., Lang J. A., Kenney W. L. Systemic lowdose aspirin and clopidogrel independently attenuate reflex cutaneous vasodilation in middle-aged humans. J. Appl. Physiol. 2010; 108: 1575–1581.

32. Maley M. J., House J. R., Tipton M. J., Eglin C. M. Role of cyclooxygenase in the vascular responses to extremity cooling in Caucasian and African males. Exp. Physiol. 2017; 102(7), 854–865.

33. Dzeka T. N., Kuzminski P., Arnold J. M. Venous responsiveness to norepinephrine in healthy subjects: effects of single doses of 325 mg aspirin. Clin. Pharmacol. Ther. 2000; 67(3), 299–304.

34. Brueggemann L. I., Mackie A. R., Mani B. K., Cribbs L. L., Byron K. L. Differential effects of selective cyclooxygenase-2 inhibitors on vascular smooth muscle ion channels may account for differences in cardiovascular risk profiles. Mol. Pharmacol. 2009; 76(5), 1053–1061.

35. Foudi N., Louedec L., Cachina T., Brink C., Norel X. Selective cyclooxygenase-2 inhibition directly increases human vascular reactivity to norepinephrine during acute inflammation. Cardiovasc. Res. 2009; 81(2), 269–277.

36. Clish C. B., Sun Y. P., Serhan C. N. Identification of dual cyclooxygenase-eicosanoid oxidoreductase inhibitors: NSAIDs that inhibit PG-LX reductase/LTB(4) dehydrogenase. Biochem. Biophys. Res. Commun. 2001; 288(4), 868–874.

37. Von der Weid P. Y., Hollenberg M. D., Fiorucci S., Wallace J. L. Aspirin-triggered, cyclooxygenase-2- -dependent lipoxin synthesis modulates vascular tone. Circulation 2004; 110(10), 1320–1325.

38. Cranston W. I., Hellon R. F., Mitchell D. Is brain prostaglandin synthesis involved in responses to cold? J. Physiol. 1975; 249(2), 425–434.

39. Pittman Q. J., Veale W.L., Cooper K. E. Observations on the effect of salicylate in fever and the regulation of body temperature against cold. Can. J. Physiol. Pharmacol. 1976; 54(2), 101–106.

40. Foster J., Mauger A. R., Chrismas B. C., Thomasson K., Taylor L. Is prostaglandin E2 (PGE2) involved in the thermogenic response to environmental cooling in healthy humans? Med. Hypotheses 2015; 85(5), 607–611.

41. Lubkowska A., Bryczkowska I., Gutowska I., Rotter I., Marczuk N., Baranowska-Bosiacka I. Banf G. The Effects of Swimming Training in Cold Water on Antioxidant Enzyme Activity and Lipid Peroxidation in Erythrocytes of Male and Female Aged Rats. Int. J. Environ. Res. Public Health 2019; 16, 647. doi:10.3390/ ijerph16040647

42. Lubkowska A., Dołęgowska B., Szyguła Z. Wholebody cryostimulation – potential beneficial treatment for improving antioxidant capacity in healthy men – significance of the number of sessions. PLoS One 2012; 7(10), e46352.

43. Walter M. F., Jacob R. F., Day C. A., Dahlborg R., Weng Y., Mason R. P. Sulfone COX-2 inhibitors increase susceptibility of human LDL and plasma to oxidative modification: comparison to sulfonamide COX-2 inhibitors and NSAIDs. Atherosclerosis 2004; 177(2), 235–243.