Excellence project PrF UHK 2216/2023–2024, University of Hradec Kralove, Hradec Kralove, Czech Republic

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Excellence project PrF UHK 2216/2023–2024, University of Hradec Kralove, Hradec Kralove, Czech Republic

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Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes

Jaćević, Vesna; Dumanović, Jelena; Grujić-Milanović, Jelica; Milovanović, Zoran; Amidžić, Ljiljana; Vojinović, Nataša; Nežić, Lana; Marković, Bojan; Dobričić, Vladimir; Milosavljević, Petar; Nepovimova, Eugenie; Kuča, Kamil

(Elsevier, 2023)

TY  - JOUR
AU  - Jaćević, Vesna
AU  - Dumanović, Jelena
AU  - Grujić-Milanović, Jelica
AU  - Milovanović, Zoran
AU  - Amidžić, Ljiljana
AU  - Vojinović, Nataša
AU  - Nežić, Lana
AU  - Marković, Bojan
AU  - Dobričić, Vladimir
AU  - Milosavljević, Petar
AU  - Nepovimova, Eugenie
AU  - Kuča, Kamil
PY  - 2023
UR  - http://rimi.imi.bg.ac.rs/handle/123456789/1342
AB  - Oxidative stress status and morphological injuries in the brain of Wistar rats induced by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, glutathione reductase, GR, and glutathione peroxidase, GPx), were estimated in the brain tissue homogenates on day 35 of the study. Brain alterations were carefully quantified by semiquantitative grading scales - brain damage score (BDS). Oxidative stress parameters, MDA and AOPP were significantly highest in the asoxime-, obidoxime- and K075-treated groups (p < 0.001). The activity of SOD and CAT was significantly elevated in the obidoxime-, K048-, and K075-treated groups (p < 0.001). Besides, GR was markedly decreased in the obidoxime- and K074-treated groups (p < 0.01), while treatment with K048, K074 and K075 induced extremely high elevation in GPx levels (p < 0.001). In the same groups of rats, brain alterations associated with polymorphonuclear cell infiltrate were significantly more severe than those observed in animals receiving only asoxime or K027 (p < 0.001). The presented results confirmed that treatment with different oximes significantly improved the oxidative status and attenuated signs of inflammation in rats' brains. Presented results, together with our previously published data can help to predict likely adverse systemic toxic effects, and target organ systems, which are crucial for establishing risk categories, as well as in dose selection of K-oximes as drug candidates.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T2  - Chemico-Biological InteractionsChem Biol Interact
T1  - Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes
SP  - 110658
VL  - 383
DO  - 10.1016/j.cbi.2023.110658
ER  - 
@article{
author = "Jaćević, Vesna and Dumanović, Jelena and Grujić-Milanović, Jelica and Milovanović, Zoran and Amidžić, Ljiljana and Vojinović, Nataša and Nežić, Lana and Marković, Bojan and Dobričić, Vladimir and Milosavljević, Petar and Nepovimova, Eugenie and Kuča, Kamil",
year = "2023",
abstract = "Oxidative stress status and morphological injuries in the brain of Wistar rats induced by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, glutathione reductase, GR, and glutathione peroxidase, GPx), were estimated in the brain tissue homogenates on day 35 of the study. Brain alterations were carefully quantified by semiquantitative grading scales - brain damage score (BDS). Oxidative stress parameters, MDA and AOPP were significantly highest in the asoxime-, obidoxime- and K075-treated groups (p < 0.001). The activity of SOD and CAT was significantly elevated in the obidoxime-, K048-, and K075-treated groups (p < 0.001). Besides, GR was markedly decreased in the obidoxime- and K074-treated groups (p < 0.01), while treatment with K048, K074 and K075 induced extremely high elevation in GPx levels (p < 0.001). In the same groups of rats, brain alterations associated with polymorphonuclear cell infiltrate were significantly more severe than those observed in animals receiving only asoxime or K027 (p < 0.001). The presented results confirmed that treatment with different oximes significantly improved the oxidative status and attenuated signs of inflammation in rats' brains. Presented results, together with our previously published data can help to predict likely adverse systemic toxic effects, and target organ systems, which are crucial for establishing risk categories, as well as in dose selection of K-oximes as drug candidates.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions, Chemico-Biological InteractionsChem Biol Interact",
title = "Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes",
pages = "110658",
volume = "383",
doi = "10.1016/j.cbi.2023.110658"
}
Jaćević, V., Dumanović, J., Grujić-Milanović, J., Milovanović, Z., Amidžić, L., Vojinović, N., Nežić, L., Marković, B., Dobričić, V., Milosavljević, P., Nepovimova, E.,& Kuča, K.. (2023). Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-Biological Interactions
Elsevier., 383, 110658.
https://doi.org/10.1016/j.cbi.2023.110658
Jaćević V, Dumanović J, Grujić-Milanović J, Milovanović Z, Amidžić L, Vojinović N, Nežić L, Marković B, Dobričić V, Milosavljević P, Nepovimova E, Kuča K. Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-Biological Interactions. 2023;383:110658.
doi:10.1016/j.cbi.2023.110658 .
Jaćević, Vesna, Dumanović, Jelena, Grujić-Milanović, Jelica, Milovanović, Zoran, Amidžić, Ljiljana, Vojinović, Nataša, Nežić, Lana, Marković, Bojan, Dobričić, Vladimir, Milosavljević, Petar, Nepovimova, Eugenie, Kuča, Kamil, "Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes" in Chemico-Biological Interactions, 383 (2023):110658,
https://doi.org/10.1016/j.cbi.2023.110658 . .
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