Uticaj proteinske dijete sa ili bez omega-3 masnih kiselina na razvoj nealkoholne masne degeneracije jetre pacova indukovane olanzapinom
Influence of protein diet with or without omega-3 fatty acids on the development of non-alcoholic fatty degeneration of olanzapine-induced rat liver
Doktorand
Mitrović, MiroslavMentor
Jakovljević, VladimirČlanovi komisije
Janjić, VladimirMilovanović, Dragan
Vučić, Vesna
Metapodaci
Prikaz svih podataka o disertacijiSažetak
U svetu ali i kod nas terapija antipsihoticima je terapija izbora u povećanju kvaliteta života pacijenata sa mentalnim poremećajima koji zbog svojih pozitivnih
osobina da skoro ne izazivaju ekstrapiramidalni sindrom. Oksidativni stres ima
važnu ulogu u patofiziologiji psihijatrijskih poremećaja. Cilj istraživanja je bio
ispitati uticaj hronične primene olanzapina na nastanak nealkoholne masne bolesti
jetre pacova koji su na hroničnoj proteinskoj ishrani sa ili bez omega 3 masnih
kiselina. Eksperimentalna studija na životinjama Wistar albino soja (n=96; starost 8
nedelja, 200 ± 20 g) in vivo i in vitro podeljenih u 8 grupa u odnosu na dijetalni režim
i farmakološki tretman.
Nakon farmakološkog i dijetalnog tretmana od 6 nedelja, životinje se žrtvuju
pri čemu bi se sprovela patohistološka i biohemijska ispitivanja. Za vizuelizaciju
struktura u histološkim sekcijama upotrebljavalo se H&E, Masson trichrome bojenja
za utvrđivanje obima morfoloških i histoloških promena i... kvantifikaciju portne
inflamacije, broja Kupffer-ovih ćelija, fokalne nekroze hepatocita i mikro i
makrovezikularnih masnih promena jetre. U homogenatu tkiva i krvi životinje
određivani su se sledeći parametri: Parametri redoks ravnoteže (superoksid anjon
radikal O2-, vodonik peroksid H2O2, indeks lipidne peroksidacije TBARS, nitriti
NO2-); katalaza (CAT), superoksid dismutaza (SOD) i redukovani glutation (GSH) i
rutinske biohemijske analize.
Olanzapin dovodi do razvoja nealkoholne masne jetre i povećanja ukupnog skora
nekroinflamatorne aktivnosti u jetri. Analizom biohemijskih parametara, utvrđeno
je da olanzapin dovodi do povećanja vrednosti glikemije, holesterola, enzima jetre
(AST i ALT), dok nije evidentiran značajan uticaj leka na LDL holesterol,
trigliceride, HDL holesterol i enzime jetre gama-GT i ukupne bilirubine.
Olanzapin poseduje snažan oksidacioni potencijal i uticaj na rast oksidativnih
slobodnih radikala. Promene su okarakterisane kao razvoj toksičnog hepatitisa
usled hronične primene leka.
In the world, but also in our country, antipsychotic therapy is the therapy of choice in increasing the quality of life of patients with mental disorders who, due to their positive
properties, almost do not cause extrapyramidal syndrome. Oxidative stress plays an important
role in the pathophysiology of psychiatric disorders. The aim of the study was to examine the
effect of chronic olanzapine administration on the development of non - alcoholic fatty liver
disease in rats on a chronic protein diet with or without omega 3 fatty acids. This was an
experimental study in animals of Wistar albino strain (n = 96; age 8 weeks, 200 ± 20 g) in
vivo and in vitro divided into 8 groups according to diet and pharmacological treatment.
After 6 weeks of pharmacological and dietary treatment, the animals were sacrificed
and pathohistological and biochemical tests are performed. For visualization of structures in
histological sections, H&E, Masson trichrome staining were used to deter...mine the extent of
morphological and histological changes and quantification of portal inflammation, Kupffer
cell number, focal hepatocyte necrosis, and micro and macro-vesicular fatty changes of the
liver. The following parameters were determined in the homogenate of animal tissue and
blood: Redox equilibrium parameters (superoxide anion radical O2-, hydrogen peroxide
H2O2, lipid peroxidation index TBARS, nitrites NO2-); catalase (CAT), superoxide dismutase
(SOD) and reduced glutathione (GSH) and routine biochemical analyzes.
Olanzapine leads to the development of non-alcoholic fatty liver and an increase in
the overall score of necro-inflammatory activity in the liver. Analysis of biochemical
parameters revealed that olanzapine leads to an increase in glycemia, cholesterol, liver
enzymes (AST and ALT), while no significant effect of the drug on LDL cholesterol,
triglycerides, HDL cholesterol and liver enzymes gamma-GT and total bilirubin was
recorded.
Olanzapine has a strong oxidative potential and influence on the growth of oxidative
free radicals. The changes were characterized as the development of toxic hepatitis due to chronic drug administration.