The distribution of opiate alkaloids in brain

U ovoj doktorskoj disertaciji je uspešno izvršeno izolovanjeopijatnih alkaloida iz humanih bioloških uzoraka (moždanogtkiva, krvi, urina i žuči) kao i bioloških uzorakaeksperimentalnih životinja (moždanog tkiva i krvi) primenompostupka čvrsto-tečne ekstrakcije (SPE-Solid Phase Extraction).Modifikovan je postupak za kvalitativnu i kvantitativnu GC-MS(Gas Chromatography-Mass Spectrometry) analizu biološkihuzoraka.Utvrđena je distribucija opijatnih alkaloida: morfina, kodeina,acetilkodeina, 6-acetilmorfina i heroina u humanim biološkimuzorcima moždanog tkiva (moždanoj kori, moždanom stablu,amigdali i bazalnim jedrima), pri čemu je najveći sadržajopijata 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 uzorcimamoždanog tkiva (moždanoj kori, moždanom stablu, amigdali ibazalnim jedrima) i krvi eksperimentalnih životinja (pacova), urazličitim vremenskim periodima (5, 15, 45 i 120 minuta) odtretiranja životinja heroinom.Najveći sadržaj opijata je određen u moždanoj kori i bazalnimjedrima, podjednako kod mužjaka i ženki pacova ali u različitimvremenskim periodima. U uzorcima krvi je najveći sadržajopijata određen u istom vremenskom periodu kod životinja obapola, pri čemu su kod mužjaka određene znatno veće vrednostikoncentracija, što ukazuje na bržudistribuciju opijata iz krvi umozak kod ženki u odnosu na mužjake pacova.Utvrđeno je da je distribucija opijata u humanom moždanomtkivu kod pripadnika suprotnih polova kao i moždanom tkivumužjaka i ženki pacova (nakon 120 minuta od tretiranjaheroinom), identična.Ispitivanjem uticaja opijata na markere oksidativnog stresa ujetri eksperimentalnih životinja suprotnih polova, utvrđeno jesmanjenje 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 withheroine. 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).