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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Pharmaceutical Association of Serbia, Belgrade, Serbia
2015-01-01
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Series: | Arhiv za farmaciju |
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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. |
first_indexed | 2024-12-16T20:52:18Z |
format | Article |
id | doaj.art-123dbc671edd461ca59103983c368d42 |
institution | Directory Open Access Journal |
issn | 0004-1963 2217-8767 |
language | srp |
last_indexed | 2024-12-16T20:52:18Z |
publishDate | 2015-01-01 |
publisher | Pharmaceutical Association of Serbia, Belgrade, Serbia |
record_format | Article |
series | Arhiv za farmaciju |
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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