title: Finasteride improves motor, EEG, and cellular changes in rat brain in thioacetamide-induced hepatic encephalopathy.
abstract: Neurosteroids are involved in the pathogenesis of hepatic encephalopathy (HE). This study evaluated the effects of finasteride, inhibitor of neurosteroid synthesis, on motor, EEG, and cellular changes in rat brain in thioacetamide-induced HE. Male Wistar rats were divided into the following groups: 1) control; 2) thioacetamide-treated group, TAA (300 mg·kg(-1)·day(-1)); 3) finasteride-treated group, FIN (50 mg·kg(-1)·day(-1)); and 4) group treated with FIN and TAA (FIN + TAA). Daily doses of TAA and FIN were administered in three subsequent days intraperitoneally, and in the FIN + TAA group FIN was administered 2 h before every dose of TAA. Motor and reflex activity was determined at 0, 2, 4, 6, and 24 h, whereas EEG activity was registered about 24 h after treatment. The expressions of neuronal (NeuN), astrocytic [glial fibrilary acidic protein (GFAP)], microglial (Iba1), and oligodendrocyte (myelin oligodendrocyte glycoprotein) marker were determined 24 h after treatment. While TAA decreased all tests, FIN pretreatment (FIN + TAA) significantly improved equilibrium, placement test, auditory startle, head shake reflex, motor activity, and exploratory behavior vs. the TAA group. Vital reflexes (withdrawal, grasping, righting and corneal reflex) together with mean EEG voltage were significantly higher (P < 0.01) in the FIN + TAA vs. the TAA group. Hippocampal NeuN expression was significantly lower in TAA vs. control (P < 0.05). Cortical Iba1 expression was significantly higher in experimental groups vs. control (P < 0.05), whereas hippocampal GFAP expression was increased in TAA and decreased in the FIN + TAA group vs. control (P < 0.05). Finasteride improves motor and EEG changes in TAA-induced HE and completely prevents the development of hepatic coma.
authors.affiliation: Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailovic," University of Belgrade, Belgrade, Serbia;
authors.forename: Dušan
authors.initials: D
authors.lastname: Mladenović
authors.affiliation: Faculty of Medicine, Institute of Medical Physiology "Richard Burian," University of Belgrade, Belgrade, Serbia;
authors.forename: Dragan
authors.initials: D
authors.lastname: Hrnčić
authors.affiliation: Faculty of Medicine, Institute of Clinical and Medical Biochemistry, University of Belgrade, Belgrade, Serbia;
authors.forename: Nataša
authors.initials: N
authors.lastname: Petronijević
authors.affiliation: Faculty of Medicine, Institute of Clinical and Medical Biochemistry, University of Belgrade, Belgrade, Serbia;
authors.forename: Gordana
authors.initials: G
authors.lastname: Jevtić
authors.affiliation: Faculty of Medicine, Institute of Pathophysiology "Ljubodrag Buba Mihailovic," University of Belgrade, Belgrade, Serbia;
authors.forename: Tatjana
authors.initials: T
authors.lastname: Radosavljević
authors.affiliation: Faculty of Medicine, Institute of Medical Physiology "Richard Burian," University of Belgrade, Belgrade, Serbia;
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rašić-Marković
authors.affiliation: Faculty of Medicine, Institute of Histology and Embryology, University of Belgrade, Belgrade, Serbia; and.
authors.forename: Nela
authors.initials: N
authors.lastname: Puškaš
authors.affiliation: Centre for Medical Biochemistry, Clinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Nebojša
authors.initials: N
authors.lastname: Maksić
authors.affiliation: Faculty of Medicine, Institute of Medical Physiology "Richard Burian," University of Belgrade, Belgrade, Serbia; solja@afrodita.rcub.bg.ac.rs.
authors.forename: Olivera
authors.initials: O
authors.lastname: Stanojlović
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004569:Electroencephalography; D005106:Exploratory Behavior; D018120:Finasteride / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000473:pathology; D008124:Locomotion; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex; D013853:Thioacetamide
chemical_list: C100745:Aif1 protein, rat; D034961:Antigens, Nuclear; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D013853:Thioacetamide; D018120:Finasteride
keywords: cellular markers; electroencephalography; motor tests