TY  - CONF
AU  - Spremo-Potparević, Biljana
AU  - Topalović, Dijana
AU  - Živković, Lada
AU  - Marković, Milica
AU  - Pirković, Andrea
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4747
AB  - Combretastatins are a class of natural phenols found in the bark of Combretum
caffrum, commonly known as South African Bush Willow. Despite having a similar
name, combretastatins are unrelated to statins, a family of cholesterol-lowering drugs.
Combretastatin A4 have been shown to be one of the most potent tubulin-depolymerizing
agent. Microtubules control chromosomal segregation and cytokinesis during mitosis
in both cancer and stromal cells and contribute to overall tumor growth. Consequently,
microtubule inhibitors interfere with cell cycle progression and induce apoptosis in
cancer cells in vitro.
The aim of this study was to investigate the potential gentoxic effect of Comretastatin
A4 (CA4) in isolated peripheral blood mononuclear cells (PBMC) in Comet assay in
order to establish is there any DNA damage in healty non-dividing cells. The aim also
was to explore potential cytotoxic activity of CA4 against human cervical carcinoma
(HeLa) cell line.
Genotoxicity of CA4 was evaluated on PBMC in a range of 9 concentrations
(from 1 nM to 200μM). Non of the tested concentrations showed genotoxiceffect.
The same range of different concentrations of CA4 (from 1 nM to 200μM) were
applied to evaluate potential cytotoxicity in a monolayer culture of HeLa cells using
the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay.
After 24h incubation with CA4, there was a significant reduction in cell viability in all
concentrations above 250 nm, while IC50 (half maximal inhibitory concentration) was
123 ± 0.06396 μM.
We concluded that CA4 does not have gentoxic effect on PBMC, and that it reduce
cell viability of cancer HeLa cell lines. These results are especialy importanat because
they showed that CA4 does not damage the DNA molecule in healthy human cells, but
achieves its cytotoxic effect on malignant cells in the same range of concentrations.
PB  - European Environmental Mutagenesis and Genomics Society (EEMGS)
C3  - 51st EEMGS and 27th SEMA meeting: Abstract book
T1  - Prospective study of cytotoxic and genotoxic effects of Combretastatin
SP  - 133
EP  - 133
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4747
ER  - 

@conference{
author = "Spremo-Potparević, Biljana and Topalović, Dijana and Živković, Lada and Marković, Milica and Pirković, Andrea",
year = "2023",
abstract = "Combretastatins are a class of natural phenols found in the bark of Combretum
caffrum, commonly known as South African Bush Willow. Despite having a similar
name, combretastatins are unrelated to statins, a family of cholesterol-lowering drugs.
Combretastatin A4 have been shown to be one of the most potent tubulin-depolymerizing
agent. Microtubules control chromosomal segregation and cytokinesis during mitosis
in both cancer and stromal cells and contribute to overall tumor growth. Consequently,
microtubule inhibitors interfere with cell cycle progression and induce apoptosis in
cancer cells in vitro.
The aim of this study was to investigate the potential gentoxic effect of Comretastatin
A4 (CA4) in isolated peripheral blood mononuclear cells (PBMC) in Comet assay in
order to establish is there any DNA damage in healty non-dividing cells. The aim also
was to explore potential cytotoxic activity of CA4 against human cervical carcinoma
(HeLa) cell line.
Genotoxicity of CA4 was evaluated on PBMC in a range of 9 concentrations
(from 1 nM to 200μM). Non of the tested concentrations showed genotoxiceffect.
The same range of different concentrations of CA4 (from 1 nM to 200μM) were
applied to evaluate potential cytotoxicity in a monolayer culture of HeLa cells using
the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay.
After 24h incubation with CA4, there was a significant reduction in cell viability in all
concentrations above 250 nm, while IC50 (half maximal inhibitory concentration) was
123 ± 0.06396 μM.
We concluded that CA4 does not have gentoxic effect on PBMC, and that it reduce
cell viability of cancer HeLa cell lines. These results are especialy importanat because
they showed that CA4 does not damage the DNA molecule in healthy human cells, but
achieves its cytotoxic effect on malignant cells in the same range of concentrations.",
publisher = "European Environmental Mutagenesis and Genomics Society (EEMGS)",
journal = "51st EEMGS and 27th SEMA meeting: Abstract book",
title = "Prospective study of cytotoxic and genotoxic effects of Combretastatin",
pages = "133-133",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4747"
}

Spremo-Potparević, B., Topalović, D., Živković, L., Marković, M.,& Pirković, A.. (2023). Prospective study of cytotoxic and genotoxic effects of Combretastatin. in 51st EEMGS and 27th SEMA meeting: Abstract book
European Environmental Mutagenesis and Genomics Society (EEMGS)., 133-133.
https://hdl.handle.net/21.15107/rcub_farfar_4747

Spremo-Potparević B, Topalović D, Živković L, Marković M, Pirković A. Prospective study of cytotoxic and genotoxic effects of Combretastatin. in 51st EEMGS and 27th SEMA meeting: Abstract book. 2023;:133-133.
https://hdl.handle.net/21.15107/rcub_farfar_4747 .

Spremo-Potparević, Biljana, Topalović, Dijana, Živković, Lada, Marković, Milica, Pirković, Andrea, "Prospective study of cytotoxic and genotoxic effects of Combretastatin" in 51st EEMGS and 27th SEMA meeting: Abstract book (2023):133-133,
https://hdl.handle.net/21.15107/rcub_farfar_4747 .

TY  - CONF
AU  - Ćuruvija, Ivana
AU  - Bufan, Biljana
AU  - Đorović, Emilija
AU  - Blagojević, Veljko
AU  - Grujić-Milanović, Jelica
AU  - Marković, Milica
AU  - Đuretić, Jasmina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5132
AB  - Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal 
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated 
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE. 
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing 
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti 
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry. 
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of 
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency, 
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal 
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was 
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats 
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and 
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater 
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more 
pronounced in aged than in young rats.
PB  - Federation of European Neuroscience Societies (FENS)
C3  - FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts
T1  - Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis
SP  - S05-250
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5132
ER  - 

@conference{
author = "Ćuruvija, Ivana and Bufan, Biljana and Đorović, Emilija and Blagojević, Veljko and Grujić-Milanović, Jelica and Marković, Milica and Đuretić, Jasmina",
year = "2022",
abstract = "Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal 
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated 
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE. 
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing 
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti 
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry. 
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of 
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency, 
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal 
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was 
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats 
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and 
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater 
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more 
pronounced in aged than in young rats.",
publisher = "Federation of European Neuroscience Societies (FENS)",
journal = "FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts",
title = "Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis",
pages = "S05-250",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5132"
}

Ćuruvija, I., Bufan, B., Đorović, E., Blagojević, V., Grujić-Milanović, J., Marković, M.,& Đuretić, J.. (2022). Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis. in FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts
Federation of European Neuroscience Societies (FENS)., S05-250.
https://hdl.handle.net/21.15107/rcub_farfar_5132

Ćuruvija I, Bufan B, Đorović E, Blagojević V, Grujić-Milanović J, Marković M, Đuretić J. Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis. in FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts. 2022;:S05-250.
https://hdl.handle.net/21.15107/rcub_farfar_5132 .

Ćuruvija, Ivana, Bufan, Biljana, Đorović, Emilija, Blagojević, Veljko, Grujić-Milanović, Jelica, Marković, Milica, Đuretić, Jasmina, "Age-dependent role of NMDA receptors in experimental autoimmune encephalomyelitis" in FENS Forum 2022, 9 - 13 July, Paris, France, Book of Abstracts (2022):S05-250,
https://hdl.handle.net/21.15107/rcub_farfar_5132 .