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Finasteride Has Regionally Different Effects on Brain Oxidative Stress and Acetylcholinesterase Activity in Acute Thioacetamide-Induced Hepatic Encephalopathy in Rats.

Mladenović D, Petronijević N, Stojković T, Velimirović M, Jevtić G, Hrnčić D, Radosavljević T, Rašić-Marković A, Maksić N, Djuric D, Stanojlović O - PLoS ONE (2015)

Bottom Line: 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<0.01).

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathophysiology "Ljubodrag Buba Mihailovic", Faculty of Medicine, University of Belgrade, Dr Subotica 9, Belgrade, Serbia.

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.

No MeSH data available.


Related in: MedlinePlus

The effect of finasteride (FIN) and thioacetamide (TAA) on plasma ammonia concentration.Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally in three subsequent days and in FIN+TAA group FIN was administered 2 h before every dose of TAA. Blood samples were collected from the right side of the heart 24 h after administration of the last dose of TAA. The significance of the difference was estimated by ANOVA with Fisher’s post hoc test (**p<0.01 vs. control).
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pone.0134434.g001: The effect of finasteride (FIN) and thioacetamide (TAA) on plasma ammonia concentration.Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally in three subsequent days and in FIN+TAA group FIN was administered 2 h before every dose of TAA. Blood samples were collected from the right side of the heart 24 h after administration of the last dose of TAA. The significance of the difference was estimated by ANOVA with Fisher’s post hoc test (**p<0.01 vs. control).

Mentions: Blood ammonia concentration was significantly higher in TAA (83.2 ± 10.3 μmol/L, p<0.01) and FIN+TAA group (79.6 ± 7.6 μmol/L, p<0.01) by comparison with control (42.4 ± 3.9 μmol/L). No significant difference in ammonia concentration was evident between TAA and FIN+TAA group (p>0.05). FIN alone also did not cause any change in ammonia concentration (Fig 1).


Finasteride Has Regionally Different Effects on Brain Oxidative Stress and Acetylcholinesterase Activity in Acute Thioacetamide-Induced Hepatic Encephalopathy in Rats.

Mladenović D, Petronijević N, Stojković T, Velimirović M, Jevtić G, Hrnčić D, Radosavljević T, Rašić-Marković A, Maksić N, Djuric D, Stanojlović O - PLoS ONE (2015)

The effect of finasteride (FIN) and thioacetamide (TAA) on plasma ammonia concentration.Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally in three subsequent days and in FIN+TAA group FIN was administered 2 h before every dose of TAA. Blood samples were collected from the right side of the heart 24 h after administration of the last dose of TAA. The significance of the difference was estimated by ANOVA with Fisher’s post hoc test (**p<0.01 vs. control).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524603&req=5

pone.0134434.g001: The effect of finasteride (FIN) and thioacetamide (TAA) on plasma ammonia concentration.Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally in three subsequent days and in FIN+TAA group FIN was administered 2 h before every dose of TAA. Blood samples were collected from the right side of the heart 24 h after administration of the last dose of TAA. The significance of the difference was estimated by ANOVA with Fisher’s post hoc test (**p<0.01 vs. control).
Mentions: Blood ammonia concentration was significantly higher in TAA (83.2 ± 10.3 μmol/L, p<0.01) and FIN+TAA group (79.6 ± 7.6 μmol/L, p<0.01) by comparison with control (42.4 ± 3.9 μmol/L). No significant difference in ammonia concentration was evident between TAA and FIN+TAA group (p>0.05). FIN alone also did not cause any change in ammonia concentration (Fig 1).

Bottom Line: 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<0.01).

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathophysiology "Ljubodrag Buba Mihailovic", Faculty of Medicine, University of Belgrade, Dr Subotica 9, Belgrade, Serbia.

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.

No MeSH data available.


Related in: MedlinePlus