Uticaj polifenola prirodnog porekla i sintetskih otvarača kalijumovih kanala na kontraktilnost izolovanog uterusa

Abstract

Prirodni polifenoli su zastupljeni u velikom broju biljnih vrsta. Kao posebni izvori rezveratrola moglo bi se izdvojiti grožđe i vino, kao njegov produkt, a naringenina grejpfrut, njegov sok, hmelj i pivo. Tokom poslednje decenije rezveratrol se našao u žiži naučne i šire javnosti kao supstanca koja usporava starenje, ima antikancerogena, antiinflamatorna, kardioprotektivna svojstva. Kao moguća mesta dejstva pokazan je veliki broj ćelijskih struktura, stoga je rezveratrol označen kao "jedan molekul - mnogo meta". Između ostalog, pokazano je da rezveratrol dovodi do relaksacije glatkih mišića mnogobrojnih krvnih sudova kao i glatkih mišića žučne kese. Kalijumovi kanali su direktno ili indirektno ukljućeni u mehanizam dejstva rezveratrola. Za razliku od njega, naringenin, pripada manje proučavanoj grupi, flavonoidima. Njegov mehanizam inhibicije kontrakcija glatkih mišića uterusa još uvek nije proučen. Pored velikog interesovanja za rezveratrol, njegov uticaj na kontraktilnost glatke muskulature uterusa nije izučavan. Stoga su ciljevi ove studije bili da ispitimo moguće inhibitorno dejstvo rezveratrola i naringenina na nekoliko eksperimentalnih modela negravidnog i gravidnog uterusa i da definišemo ulogu kalijumovih kanala u tim mehanizmima dejstva. Nepoželjna kontraktilnost uterusa je uzrok poremećaja kao što su dismenoreja, kod negravidnog, a prevremeni porođaj, kod gravidnog uterusa. Do danas, ni jedan od ovih problema nije farmakološki rešen. Dismenoreja se uglavnom tretira nesteroidnim antiinflamatornim lekovima, koji nisu uspešni kod svih pacijenata i imaju izrazite neželjene efekte. Dodatno, prevremeni porođaj je uzrok morbiditeta novorođenčati u 50 % slučajeva. Malo je dokaza da lekovi koji se koriste za suzbijanje prevremenih kontrakcija zaista efikasni. Prevremeni porođaj je češći i ozbiljniji problem u grupi pacijenkinja iz progrma in vitro oplodnje. Shodno tome, idealno sredstvo za prevenciju i lečenje neželjene kontraktilnosti uterusa još uvek nije pronađen...

Natural polyphenols are present in the large number of plant species. As special sources of resveratrol are grapes and wine, as well as its products, but also naringenin grapefruit sort, its juice, hop and beer. During the last decade, resveratrol was in the focus of scientific and wider public as a substance that slows aging, has anti-cancer, anti-inflammatory, cardio-protective properties. As a possible site of action is shown by a large number of cellular structures, thus resveratrol is labeled as "one molecule - many targets". Among other things, it has been shown that resveratrol induces relaxation of smooth muscle of numerous blood vessels and smooth muscle of the gall bladder. Potassium channels are directly or indirectly involved in the mechanism of action of resveratrol. Unlike resveratrol, naringenin belongs to the group being studied less, flavonoids. Its mechanism of inhibition of the contraction of uterine smooth muscle has not been studied. In addition to the great interest in resveratrol, its effects on the contractility of smooth muscles of the uterus have not been studied. Therefore, the aims of this study were to investigate the possible inhibitory effect of resveratrol and naringenin in several experimental models of pregnant and non pregnant uterus and to define the role of potassium channels in these mechanisms of action. Irregular contractility of the uterus is the cause of the disorder, such as dysmenorrhoea in the non-gravid uterus, or premature labor in the pregnant uterus. To date, none of these problems is pharmacologically resolved. Dysmenorrhea is generally treated by non-steroidal anti- inflammatory drugs, which have not been successful for all patients, and have significant side effects. In addition, premature birth is the cause of newborn morbidity in 50% of cases. There is little evidence that the drugs used to combat premature contractions are really effective. Preterm birth is a common and serious problem in the female patients from in vitro fertilization program. Accordingly, an ideal tool for the prevention and treatment of unwanted uterine contractility has not been found yet.