Uticaj proteinske dijete sa ili bez omega-3 masnih kiselina na razvoj nealkoholne masne degeneracije jetre pacova indukovane olanzapinom

Abstract

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 determine 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.