title: Finasteride Has Regionally Different Effects on Brain Oxidative Stress and Acetylcholinesterase Activity in Acute Thioacetamide-Induced Hepatic Encephalopathy in Rats.
abstract: Finasteride (FIN) inhibits neurosteroid synthesis and potentially improves the course of hepatic encephalopathy (HE). This study aimed to investigate the effects of FIN on brain oxidative stress and acetylcholinesterase (AchE) activity in acute thioacetamide-induced HE in rats. Male Wistar rats were divided into groups: 1. control; 2. thioacetamide-treated group (TAA; 900 mg/kg); 3. finasteride-treated group (FIN; 150 mg/kg); 4. group treated with FIN and TAA (FIN+TAA). Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally during three days and in FIN+TAA group FIN was administered 2h before every dose of TAA. FIN pretreatment prevented TAA-induced rise in malondialdehyde level in the cortex due to restoration of catalase activity and increased expression of superoxide dismutase 1 (SOD1) and induced an increase in malondialdehyde level in the thalamus due to reduction of glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Although FIN pretreatment did not affect malondialdehyde level in hippocampus and caudate nucleus, hippocampal SOD1 expression was higher (p<0.05) and GR activity lower in FIN+TAA vs. TAA group (p<0.05). GPx activity was lower in caudate nucleus in FIN+TAA vs. TAA group (p<0.01). FIN pretreatment prevented TAA-induced rise in AchE activity in the thalamus and caudate nucleus and AchE activity correlates inversely in the thalamus (p<0.05) and positively in caudate nucleus (p<0.01) with malondialdehyde level. FIN has regionally selective effects on oxidative stress and AchE activity in the brain in acute TAA-induced HE in rats. The prooxidant role of FIN in the thalamus may be causally linked with inhibition of AchE.
authors.affiliation: Institute of Pathophysiology "Ljubodrag Buba Mihailovic", Faculty of Medicine, University of Belgrade, Dr Subotica 9, Belgrade, Serbia.
authors.forename: Dušan
authors.initials: D
authors.lastname: Mladenović
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Pasterova 2, Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Petronijević
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Pasterova 2, Belgrade, Serbia.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Stojković
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Pasterova 2, Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Velimirović
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Pasterova 2, Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Jevtić
authors.affiliation: Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Višegradska 26/II, Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Hrnčić
authors.affiliation: Institute of Pathophysiology "Ljubodrag Buba Mihailovic", Faculty of Medicine, University of Belgrade, Dr Subotica 9, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Radosavljević
authors.affiliation: Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Višegradska 26/II, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rašić-Marković
authors.affiliation: Centre for Medical Biochemistry, Clinical Centre of Serbia, Pasterova 2, Belgrade, Serbia.
authors.forename: Nebojša
authors.initials: N
authors.lastname: Maksić
authors.affiliation: Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Višegradska 26/II, Belgrade, Serbia.
authors.forename: Dragan
authors.initials: D
authors.lastname: Djuric
authors.affiliation: Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Višegradska 26/II, Belgrade, Serbia.
authors.forename: Olivera
authors.initials: O
authors.lastname: Stanojlović
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D018120:Finasteride / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013853:Thioacetamide
chemical_list: D058891:5-alpha Reductase Inhibitors; D013853:Thioacetamide; D008315:Malondialdehyde; D018120:Finasteride; D002374:Catalase; D005979:Glutathione Peroxidase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000110:Acetylcholinesterase