Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes
Само за регистроване кориснике
2023
Аутори
Jaćević, VesnaDumanović, Jelena
Grujić-Milanović, Jelica
Milovanović, Zoran
Amidžić, Ljiljana
Vojinović, Nataša
Nežić, Lana
Marković, Bojan
Dobričić, Vladimir
Milosavljević, Petar
Nepovimova, Eugenie
Kuča, Kamil
Метаподаци
Приказ свих података о документуАпстракт
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). Bes...ides, 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.
Кључне речи:
Oxidative stress / Brain / Oximes / Pathohistology / Subacute toxicityИзвор:
Chemico-biological interactions, 2023, 383, 110658-Издавач:
- Elsevier B.V.
Финансирање / пројекти:
- The Medical Faculty of the Military Medical Academy, University of Defence in Belgrade, Republic of Serbia (MFVMA01/23–25)
- The Excellence project PrF UHK 2216/2023–2024 University of Hradec Kralove, Hra- dec Kralove, Czech Republic.
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200015 (Универзитет у Београду, Институт за медицинска истраживања) (RS-MESTD-inst-2020-200015)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: 10.1016/j.cbi.2023.110658
ISSN: 1872-7786
PubMed: 37572873
Scopus: 2-s2.0-85171599965
Институција/група
PharmacyJaćević, 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 B.V.., 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 . .