Distribucija opijatnih alkaloida u mozgu

Abstract

U ovoj doktorskoj disertaciji je uspešno izvršeno izolovanje opijatnih alkaloida iz humanih bioloških uzoraka (moždanog tkiva, krvi, urina i žuči) kao i bioloških uzoraka eksperimentalnih životinja (moždanog tkiva i krvi) primenom postupka čvrsto-tečne ekstrakcije (SPE-Solid Phase Extraction). Modifikovan je postupak za kvalitativnu i kvantitativnu GC-MS (Gas Chromatography-Mass Spectrometry) analizu bioloških uzoraka. Utvrđena je distribucija opijatnih alkaloida: morfina, kodeina, acetilkodeina, 6-acetilmorfina i heroina u humanim biološkim uzorcima moždanog tkiva (moždanoj kori, moždanom stablu, amigdali i bazalnim jedrima), pri čemu je najveći sadržaj opijata određen u moždanoj kori i bazalnim jedrima, podjednako kod muških i ženskih osoba. Utvrđena je distribucija opijatnih alkaloida: morfina, kodeina, acetilkodeina, 6-acetilmorfina i heroina u biološkim uzorcima moždanog tkiva (moždanoj kori, moždanom stablu, amigdali i bazalnim jedrima) i krvi eksperimentalnih životinja (pacova), u različitim vremenskim periodima (5, 15, 45 i 120 minuta) od tretiranja životinja heroinom. Najveći sadržaj opijata je određen u moždanoj kori i bazalnim jedrima, podjednako kod mužjaka i ženki pacova ali u različitim vremenskim periodima. U uzorcima krvi je najveći sadržaj opijata određen u istom vremenskom periodu kod životinja oba pola, pri čemu su kod mužjaka određene znatno veće vrednosti koncentracija, što ukazuje na bržudistribuciju opijata iz krvi u mozak kod ženki u odnosu na mužjake pacova. Utvrđeno je da je distribucija opijata u humanom moždanom tkivu kod pripadnika suprotnih polova kao i moždanom tkivu mužjaka i ženki pacova (nakon 120 minuta od tretiranja heroinom), identična. Ispitivanjem uticaja opijata na markere oksidativnog stresa u jetri eksperimentalnih životinja suprotnih polova, utvrđeno je smanjenje aktivnosti enzima: katalaze (CAT), glutation-peroksidaze (GSH- Px), peroksidaze (Px) i ksantin-oksidaze (XOD).

Opiate alkaloids were successfully isolated from human biological samples (brain tissue, blood, urine, and bile) as well as from biological samples of experimental animals (brain tissue and blood) by applying procedure of solid-phase extraction (SPE). A modified procedure was worked out for qualitative and quantitative analysis of biological samples by gas chromatography-mass spectrometry (GC-MS). The distribution of opiate alkaloids:morphine, codeine, acetylcodeine, 6-acetylmorphine, and heroine in human biological samples of brain tissue (cortex, brain stem, amigdala and basal nuclei) was established, showing the highest content of opiates in the cortex and basal nuclei, equal with male and female persons. It was established how the opiatealkaloids: morphine codeine, acetylcodeine, 6-acetylmorphine and heroine are distributed in biological samples of brain tissue (cortex, brain stem, amigdala and basal nuclei) and blood of experimental animals (rats) in different time periods (5, 15, 45 and 120 min) after the animal treatment with heroine. The highest content of opiates was found in the cortex and basal nuclei, equal in the male and female rats, but in different time periods. In blood samples, the highest content of opiates was measured in the same period with animals of both sexes, the concentration in the males being significantly higher, indicating a faster passage of the opiates from blood to brain in the female compared to male rats. Identical distribution of opiates was found in human brain tissue of both male and female subjects as in rats of both sexes (120 min after treatment with heroine). Study of the effect of opiates on the markers of oxidative stress in the liver of tested animals of opposite sexes showed a lowered activity of the following enzymes: catalase (CAT), glutathion-peroxidase (GSH-Px), peroxidase (Px) and xanthine-xidase (XOD).