TY  - JOUR
AU  - Jaćević, Vesna
AU  - Grujić-Milanović, Jelica
AU  - Milovanović, Zoran
AU  - Nežić, Lana
AU  - Amidžić, Ljiljana
AU  - Vojinović, Nataša
AU  - Marković, Bojan
AU  - Dobričić, Vladimir
AU  - Milosavljević, Petar
AU  - Nepovimova, Eugenie
AU  - Kuča, Kamil
PY  - 2024
PY  - Elsevier Ireland Ltd
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5702
AB  - Oxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, 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, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats
VL  - 399
DO  - 10.1016/j.cbi.2024.111138
ER  - 

@article{
author = "Jaćević, Vesna and Grujić-Milanović, Jelica and Milovanović, Zoran and Nežić, Lana and Amidžić, Ljiljana and Vojinović, Nataša and Marković, Bojan and Dobričić, Vladimir and Milosavljević, Petar and Nepovimova, Eugenie and Kuča, Kamil",
year = "2024, Elsevier Ireland Ltd",
abstract = "Oxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, 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, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats",
volume = "399",
doi = "10.1016/j.cbi.2024.111138"
}

Jaćević, V., Grujić-Milanović, J., Milovanović, Z., Nežić, L., Amidžić, L., Vojinović, N., Marković, B., Dobričić, V., Milosavljević, P., Nepovimova, E.,& Kuča, K.. (2024). Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 399.
https://doi.org/10.1016/j.cbi.2024.111138

Jaćević V, Grujić-Milanović J, Milovanović Z, Nežić L, Amidžić L, Vojinović N, Marković B, Dobričić V, Milosavljević P, Nepovimova E, Kuča K. Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats. in Chemico-Biological Interactions. 2024;399.
doi:10.1016/j.cbi.2024.111138 .

Jaćević, Vesna, Grujić-Milanović, Jelica, Milovanović, Zoran, Nežić, Lana, Amidžić, Ljiljana, Vojinović, Nataša, Marković, Bojan, Dobričić, Vladimir, Milosavljević, Petar, Nepovimova, Eugenie, Kuča, Kamil, "Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats" in Chemico-Biological Interactions, 399 (2024),
https://doi.org/10.1016/j.cbi.2024.111138 . .

TY  - JOUR
AU  - Gajić Bojić, Milica
AU  - Treven, Marco
AU  - Pandey, Kamal P
AU  - Tiruveedhula, Phani Babu V V N
AU  - Santrač, Anja
AU  - Đukanović, Đorđe
AU  - Vojinović, Nataša
AU  - Amidžić, Ljiljana
AU  - Škrbić, Ranko
AU  - Scholze, Petra
AU  - Ernst, Margot
AU  - Cook, James M
AU  - Savić, Miroslav
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5619
AB  - Hypotensive influences of benzodiazepines and other GABAA receptor ligands, recognized in clinical practice, seem to stem from the existence of “vascular” GABAA receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABAA receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABAA γ 2 and α1-5 subunit proteins. To confirm the role of “vascular” GABAA receptors, we investigated the vascular effects of standard benzodiazepines, mida-zolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5β3γ 2 over other αxβ3γ 2 GABAA receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazo-lam, both of which at 100 μmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABAA receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.
PB  - Canadian Science Publishing
T2  - Canadian  Journal of Physiology and  Pharmacology
T1  - Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta
VL  - 102
IS  - 3
SP  - 206
EP  - 217
DO  - 10.1139/cjpp-2023-0285
ER  - 

@article{
author = "Gajić Bojić, Milica and Treven, Marco and Pandey, Kamal P and Tiruveedhula, Phani Babu V V N and Santrač, Anja and Đukanović, Đorđe and Vojinović, Nataša and Amidžić, Ljiljana and Škrbić, Ranko and Scholze, Petra and Ernst, Margot and Cook, James M and Savić, Miroslav",
year = "2024",
abstract = "Hypotensive influences of benzodiazepines and other GABAA receptor ligands, recognized in clinical practice, seem to stem from the existence of “vascular” GABAA receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABAA receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABAA γ 2 and α1-5 subunit proteins. To confirm the role of “vascular” GABAA receptors, we investigated the vascular effects of standard benzodiazepines, mida-zolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5β3γ 2 over other αxβ3γ 2 GABAA receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazo-lam, both of which at 100 μmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABAA receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.",
publisher = "Canadian Science Publishing",
journal = "Canadian  Journal of Physiology and  Pharmacology",
title = "Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta",
volume = "102",
number = "3",
pages = "206-217",
doi = "10.1139/cjpp-2023-0285"
}

Gajić Bojić, M., Treven, M., Pandey, K. P., Tiruveedhula, P. B. V. V. N., Santrač, A., Đukanović, Đ., Vojinović, N., Amidžić, L., Škrbić, R., Scholze, P., Ernst, M., Cook, J. M.,& Savić, M.. (2024). Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta. in Canadian  Journal of Physiology and  Pharmacology
Canadian Science Publishing., 102(3), 206-217.
https://doi.org/10.1139/cjpp-2023-0285

Gajić Bojić M, Treven M, Pandey KP, Tiruveedhula PBVVN, Santrač A, Đukanović Đ, Vojinović N, Amidžić L, Škrbić R, Scholze P, Ernst M, Cook JM, Savić M. Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta. in Canadian  Journal of Physiology and  Pharmacology. 2024;102(3):206-217.
doi:10.1139/cjpp-2023-0285 .

Gajić Bojić, Milica, Treven, Marco, Pandey, Kamal P, Tiruveedhula, Phani Babu V V N, Santrač, Anja, Đukanović, Đorđe, Vojinović, Nataša, Amidžić, Ljiljana, Škrbić, Ranko, Scholze, Petra, Ernst, Margot, Cook, James M, Savić, Miroslav, "Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta" in Canadian  Journal of Physiology and  Pharmacology, 102, no. 3 (2024):206-217,
https://doi.org/10.1139/cjpp-2023-0285 . .

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 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 . .