Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats

The present study was directed to potentially beneficial effects of agmatine (AGM) on oxidative/nitrosative stress development in selective vulnerable brain regions during chlorpromazine (HPZ) treatment in rats. All tested compounds were administered intraperitoneally (i.p.) in one single dose. The...

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Main Authors: Dejanović Bratislav, Ninković Milica, Stojanović Ivana, Lavrnja Irena, Radičević Tatjana, Stevanović Ivana
Format: Article
Language:srp
Published: Pharmaceutical Association of Serbia, Belgrade, Serbia 2015-01-01
Series:Arhiv za farmaciju
Subjects:
Online Access:https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2015/0004-19631506329D.pdf
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author Dejanović Bratislav
Ninković Milica
Stojanović Ivana
Lavrnja Irena
Radičević Tatjana
Stevanović Ivana
author_facet Dejanović Bratislav
Ninković Milica
Stojanović Ivana
Lavrnja Irena
Radičević Tatjana
Stevanović Ivana
author_sort Dejanović Bratislav
collection DOAJ
description The present study was directed to potentially beneficial effects of agmatine (AGM) on oxidative/nitrosative stress development in selective vulnerable brain regions during chlorpromazine (HPZ) treatment in rats. All tested compounds were administered intraperitoneally (i.p.) in one single dose. The animals were divided into control (K, 0.9 % saline solution), HPZ (HPZ, 38.7 mg/kg b.w.), HPZ+AGM (AGM, 75 mg/kg b.w. immediately after HPZ, 38.7 mg/kg b.w. i.p.) and AGM (AGM, 75 mg/kg b.w.) groups. Rats were sacrificed by decapitation 24 hours after the treatment. Analysis of data showed that HPZ+AGM injection significantly decreased drug concentration compared with HPZ-animals (p<0.05). HPZ application increased lipid peroxidation (p<0.001 in cortex, striatum and hippocampus), nitrite and nitrate concentration (p<0.001 in all three brain regions) and superoxide anion production (p<0.05 in all three brain structures), while completely damaged enzymatic antioxidative defense system (superoxide dismutase in both cortex and striatum p<0.05 and hippocampus p<0.001; glutathion reductase in both cortex and striatum p<0.001 and hippocampus p<0.05; catalase in cortex p<0.001 and both striatum and hippocampus p<0.05). However, treatment with AGM significantly attenuated the oxidative stress parameters compared to HPZ-group (lipid peroxidation in cortex p<0.001, striatum p<0.01 and hippocampus p<0.05; nitrite and nitrate concentration in all three brain structures p<0.001) and restores antioxidant capacity to control values in all examined brain structures. Immunohistochemical staining of GFAP molecules in rats showed an increase in the number of positive cells 24 h after acute HPZ-administration. All these results indicate that AGM may be effective in the protection of HPZ-induced brain injury in rats.
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spelling doaj.art-123dbc671edd461ca59103983c368d422022-12-21T22:16:45ZsrpPharmaceutical Association of Serbia, Belgrade, SerbiaArhiv za farmaciju0004-19632217-87672015-01-0165632934910.5937/arhfarm1506329D0004-19631506329DAgmatine prevents acute chlorpromazine-induced neurotoxicity in ratsDejanović Bratislav0Ninković Milica1Stojanović Ivana2Lavrnja Irena3https://orcid.org/0000-0002-0607-5594Radičević Tatjana4Stevanović Ivana5Vojnomedicinski centar 'Karaburma', Beograd, SerbiaInstitut za medicinska istraživanja, Vojnomedicinska akademija, Beograd, SerbiaInstitut za biohemiju, Medicinski fakultet, Univerzitet u Nišu, Niš, SerbiaInstitut za biološka istraživanja 'Siniša Stanković', Univerzitet u Beogradu, Beograd, SerbiaInstitut za higijenu i tehnologiju mesa, Beograd, SerbiaInstitut za medicinska istraživanja, Vojnomedicinska akademija, Beograd, SerbiaThe present study was directed to potentially beneficial effects of agmatine (AGM) on oxidative/nitrosative stress development in selective vulnerable brain regions during chlorpromazine (HPZ) treatment in rats. All tested compounds were administered intraperitoneally (i.p.) in one single dose. The animals were divided into control (K, 0.9 % saline solution), HPZ (HPZ, 38.7 mg/kg b.w.), HPZ+AGM (AGM, 75 mg/kg b.w. immediately after HPZ, 38.7 mg/kg b.w. i.p.) and AGM (AGM, 75 mg/kg b.w.) groups. Rats were sacrificed by decapitation 24 hours after the treatment. Analysis of data showed that HPZ+AGM injection significantly decreased drug concentration compared with HPZ-animals (p<0.05). HPZ application increased lipid peroxidation (p<0.001 in cortex, striatum and hippocampus), nitrite and nitrate concentration (p<0.001 in all three brain regions) and superoxide anion production (p<0.05 in all three brain structures), while completely damaged enzymatic antioxidative defense system (superoxide dismutase in both cortex and striatum p<0.05 and hippocampus p<0.001; glutathion reductase in both cortex and striatum p<0.001 and hippocampus p<0.05; catalase in cortex p<0.001 and both striatum and hippocampus p<0.05). However, treatment with AGM significantly attenuated the oxidative stress parameters compared to HPZ-group (lipid peroxidation in cortex p<0.001, striatum p<0.01 and hippocampus p<0.05; nitrite and nitrate concentration in all three brain structures p<0.001) and restores antioxidant capacity to control values in all examined brain structures. Immunohistochemical staining of GFAP molecules in rats showed an increase in the number of positive cells 24 h after acute HPZ-administration. All these results indicate that AGM may be effective in the protection of HPZ-induced brain injury in rats.https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2015/0004-19631506329D.pdfagmatineantioxidant defensebrainchlorpromazineoxidative stress
spellingShingle Dejanović Bratislav
Ninković Milica
Stojanović Ivana
Lavrnja Irena
Radičević Tatjana
Stevanović Ivana
Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats
Arhiv za farmaciju
agmatine
antioxidant defense
brain
chlorpromazine
oxidative stress
title Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats
title_full Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats
title_fullStr Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats
title_full_unstemmed Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats
title_short Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats
title_sort agmatine prevents acute chlorpromazine induced neurotoxicity in rats
topic agmatine
antioxidant defense
brain
chlorpromazine
oxidative stress
url https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2015/0004-19631506329D.pdf
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AT ninkovicmilica agmatinepreventsacutechlorpromazineinducedneurotoxicityinrats
AT stojanovicivana agmatinepreventsacutechlorpromazineinducedneurotoxicityinrats
AT lavrnjairena agmatinepreventsacutechlorpromazineinducedneurotoxicityinrats
AT radicevictatjana agmatinepreventsacutechlorpromazineinducedneurotoxicityinrats
AT stevanovicivana agmatinepreventsacutechlorpromazineinducedneurotoxicityinrats