Efekti akutno i subhronično primenjenog DL-metionina na markere oksidativnog stresa u plazmi i aktivnost acetilholinesteraze u tkivu srca pacova

  • Žarko Mićović Ministry of Defence, Military Health Department, Belgrade, Serbia
  • Sanja Kostić University of Belgrade, Faculty of Medicine, Institute of Medical Physiology „Richard Burian“, Belgrade, Serbia
  • Slavica Mutavdžin University of Belgrade, Faculty of Medicine, Institute of Medical Physiology „Richard Burian“, Belgrade, Serbia
  • Aleksa Andrejević University of Priština – Kosovska Mitrovica, Faculty of Medical Medicine, Clinic of Gynecology and Obstetrics, Kosovska Mitrovica, Serbia
  • Aleksandra Stamenković University of Manitoba, St. Boniface Hospital Research Center, §Institute of Cardiovascular Sciences, Winnipeg, Canada
  • Mirjana Čolović University of Belgrade, Vinča Institute of Nuclear Sciences, Department of Physical Chemistry, Belgrade, Serbia
  • Danijela Krstić University of Belgrade, Faculty of Medicine, Institute of Medical Chemistry, Belgrade, Serbia
  • Marko Djurić University Clinical Hospital Center „Dr Dragiša Mišović – Dedinje“, Department of Anesthesiology, Reanimatology and Intensive Care Medicine, Belgrade, Serbia
  • Dragan Hrnčić University of Belgrade, Faculty of Medicine, Institute of Medical Physiology „Richard Burian“, Belgrade, Serbia
  • Vladimir Živković University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Kragujevac, Serbia
  • Vladimir Jakovljević University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Kragujevac, Serbia
  • Dragan Djurić University of Belgrade, Faculty of Medicine, Institute of Medical Physiology „Richard Burian“, Belgrade, Serbia
Ključne reči: stres, oksidativni, metionin, homocistein, pacovi, plazma, enzimi, holinesteraze

Sažetak


Uvod/Cilj. Hronično indukovana hipermetioninemija dovodi do hiperhomocisteinemije koja izaziva oksidativni stress, aterogenezu, neurodegeneraciju i karcinome. Međutim, malo se zna o efektima akutne i subhronične primene DL-metionina (Met). Cilj ovog istraživanja bila je procena efekata akutno i subhronično primenjenog Met na parametre oksidativnog stresa u plazmi pacova [enzime: katalaza (CAT), glutation peroksidaza (GPx), superoksid dismutaza (SOD) i indeks lipidne peroksidacije, malondialdehid (MDA)] i na aktivnost acetilholinesteraze (AChE) u tkivu srca pacova. Metode. Aktivnosti enzima, kao i koncentracija MDA mereni su nakon akutne (n = 8) i subhronične (n = 10) primene Met (i.p. 0,8 mmoL/kg u jednoj dozi u akutnom eksperimentu ili svakodnevno tokom tri nedelje u subhroničnom eksperimentu). Isti način tretmana je bio primenjen i u kontrolnoj grupi, ali su životinje bile tretirane fiziološkim rastvorom [i.p. 1 mL 0,9% NaCl (n = 8) u akutnom i 0,1–0,2 mL 0,9% NaCl svakodnevno tokom tri nedelje (n = 10), u subhroničnom eksperimentu]. Testirani parametri su mereni 60 min nakon aplikacije supstanci u akutnim eksperimentima i nakon tri nedelje tretmana u subhroničnim eksperimentima. Rezultati. Nije bilo razlike u vrednostima homocisteina između grupe tretirane Met tokom tri nedelje i kontrolne grupe. Primena Met značajno je povećala aktivnost CAT i GPx nakon 1h u poređenju sa kontrolnom grupom (p = 0,008 za oba enzima), dok je aktivnost SOD i koncentracija MDA bila nepromenjena. Subhronično primenjen Met nije uticao na aktivnost antioksidativnih enzima, ni na koncentraciju MDA u plazmi. Aktivnost AChE u srčanom tkivu pacova nije se menjala nakon 1 h, ali je bila značajno smanjena nakon subhroničnog tretmana (p = 0,041). Zaključak. Rezultati istraživanja pokazuju da Met različito utiče na ispitivane parametre tokom akutne i hronične primene. Posle akutne primene Met mobiliše veći deo antioksidativnih enzima, dok se tokom subhroničnog tretmana ove promene gube. Nasuprot tome, akutna primena Met ne utiče na aktivnost AChE, dok duže trajanje metioninskog opterećenja smanjuje funkciju ovog enzima. Ovi nalazi ukazuju na to da metionin može da interferira sa antioksidativnim sistemom zaštite i holinergičkom kontrolom funkcije srca.

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