Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily.... more Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (CI(-), Br(-), I(-) and SCN(-)) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore, MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity.
European review for medical and pharmacological sciences, 2011
The aim of this study was to evaluate the effects of two nutraceuticals Amazon Megamin and Immuna... more The aim of this study was to evaluate the effects of two nutraceuticals Amazon Megamin and Immunarc forte in radiorecovery of human lymphocytes after exposure to ionizing radiation in vitro. The incidences of micronuclei, cell proliferation, apoptosis and lipid peroxidation products were examined in cultured human peripheral blood lymphocytes before and after ionizing radiation in a present of nutraceuticals in vitro. Results showed that Amazon Megamin and Immunarc forte possess antioxidant properties; they act by eliminating the toxic metabolites, scavenging the free radicals and decreasing lipid peroxidation. The obtained results indicated that the studied nutraceuticals can help in prevention of the development of injurious caused by ionizing irradiation and, therefore, they encourage studies on their radioprotective properties.
ABSTRACT In this paper we present the data of lymphocyte radiosensitivity testing used for charac... more ABSTRACT In this paper we present the data of lymphocyte radiosensitivity testing used for characterization of radiosensitive cellular phenotype and diagnostics of ataxia-telangiectasia disease. We point out the advantage of lymphocyte micronucleus test (CBMN) over other cellular tests for assessment of radiosensitivity: the first advantage of CBMN is that primary patient cells are used (less than 1 ml), the second one is that the results of testing are obtained within 3 days and there is no need for establishing a patient-derived cell line, which requires additional time and application of more expensive methods. The third advantage of CBMN method is that it gives information about proliferative ability of cells, which can recognize dysfunctional ataxia-telangiectasia mutated protein. The results are fast and accurate in diagnostics of ataxia-telagiectasia diseases.
Genomic instability tends to occur at specific genomic regions known as common fragile sites (FS)... more Genomic instability tends to occur at specific genomic regions known as common fragile sites (FS). FS are evolutionarily conserved and generally involve late replicating regions with AT-rich sequences. The possible correlation between some FS and cancer-related breakpoints emphasizes on the importance of understanding the mechanisms of chromosomal instability at these sites. Although about 230 FS have already been mapped cytogenetically, only a few of them have been characterized on a molecular level. In this chapter, we provide a protocol for mapping of common FS using bacterial artificial chromosome (BAC) probes in fluorescence in situ hybridization (FISH) and suggest the usage of lymphocytes from Fanconi anemia patients as a model system. In the latter, rare FS are expressed much more frequently than in, for example, aphidicolin-induced blood lymphocyte preparations. Knowing the exact location of FS enables the molecular comparison of their location and breakpoints that appear during evolution, cancer development and inherited disorders.
Carbon nanotubes are unique one-dimensional macromolecules with promising application in biology ... more Carbon nanotubes are unique one-dimensional macromolecules with promising application in biology and medicine. Since their toxicity is still under debate, here we describe an investigation of genotoxic properties of purified single-walled carbon nanotubes (SWCNT), multiwall carbon nanotubes (MWCNT), and amide-functionalized purified SWCNT. We used two different cell systems: cultured human lymphocytes where we employed cytokinesis-block micronucleus test and human fibroblasts where we investigate the induction of DNA double-strand breaks (DSBs) employing H2AX phosphorylation assay.
Herbal radiomodulators: applications in medicine, homeland defence and space, 2008
... 301325. Arora, R., Chawla, R., Singh, S., Sagar, RK, Kumar, R., Sharma, A., Prasad, J., Sing... more ... 301325. Arora, R., Chawla, R., Singh, S., Sagar, RK, Kumar, R., Sharma, A., Prasad, J., Singh, S., Gurudutta, GU and Sharma, RK (2006b ... Jagetia, GC, Venkatesh, P. and Baliga, MS (2003) Evaluation of the radioprotective effect of Aegle marmelos (L.) Correa in cultured human ...
Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily.... more Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (CI(-), Br(-), I(-) and SCN(-)) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore, MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity.
European review for medical and pharmacological sciences, 2011
The aim of this study was to evaluate the effects of two nutraceuticals Amazon Megamin and Immuna... more The aim of this study was to evaluate the effects of two nutraceuticals Amazon Megamin and Immunarc forte in radiorecovery of human lymphocytes after exposure to ionizing radiation in vitro. The incidences of micronuclei, cell proliferation, apoptosis and lipid peroxidation products were examined in cultured human peripheral blood lymphocytes before and after ionizing radiation in a present of nutraceuticals in vitro. Results showed that Amazon Megamin and Immunarc forte possess antioxidant properties; they act by eliminating the toxic metabolites, scavenging the free radicals and decreasing lipid peroxidation. The obtained results indicated that the studied nutraceuticals can help in prevention of the development of injurious caused by ionizing irradiation and, therefore, they encourage studies on their radioprotective properties.
ABSTRACT In this paper we present the data of lymphocyte radiosensitivity testing used for charac... more ABSTRACT In this paper we present the data of lymphocyte radiosensitivity testing used for characterization of radiosensitive cellular phenotype and diagnostics of ataxia-telangiectasia disease. We point out the advantage of lymphocyte micronucleus test (CBMN) over other cellular tests for assessment of radiosensitivity: the first advantage of CBMN is that primary patient cells are used (less than 1 ml), the second one is that the results of testing are obtained within 3 days and there is no need for establishing a patient-derived cell line, which requires additional time and application of more expensive methods. The third advantage of CBMN method is that it gives information about proliferative ability of cells, which can recognize dysfunctional ataxia-telangiectasia mutated protein. The results are fast and accurate in diagnostics of ataxia-telagiectasia diseases.
Genomic instability tends to occur at specific genomic regions known as common fragile sites (FS)... more Genomic instability tends to occur at specific genomic regions known as common fragile sites (FS). FS are evolutionarily conserved and generally involve late replicating regions with AT-rich sequences. The possible correlation between some FS and cancer-related breakpoints emphasizes on the importance of understanding the mechanisms of chromosomal instability at these sites. Although about 230 FS have already been mapped cytogenetically, only a few of them have been characterized on a molecular level. In this chapter, we provide a protocol for mapping of common FS using bacterial artificial chromosome (BAC) probes in fluorescence in situ hybridization (FISH) and suggest the usage of lymphocytes from Fanconi anemia patients as a model system. In the latter, rare FS are expressed much more frequently than in, for example, aphidicolin-induced blood lymphocyte preparations. Knowing the exact location of FS enables the molecular comparison of their location and breakpoints that appear during evolution, cancer development and inherited disorders.
Carbon nanotubes are unique one-dimensional macromolecules with promising application in biology ... more Carbon nanotubes are unique one-dimensional macromolecules with promising application in biology and medicine. Since their toxicity is still under debate, here we describe an investigation of genotoxic properties of purified single-walled carbon nanotubes (SWCNT), multiwall carbon nanotubes (MWCNT), and amide-functionalized purified SWCNT. We used two different cell systems: cultured human lymphocytes where we employed cytokinesis-block micronucleus test and human fibroblasts where we investigate the induction of DNA double-strand breaks (DSBs) employing H2AX phosphorylation assay.
Herbal radiomodulators: applications in medicine, homeland defence and space, 2008
... 301325. Arora, R., Chawla, R., Singh, S., Sagar, RK, Kumar, R., Sharma, A., Prasad, J., Sing... more ... 301325. Arora, R., Chawla, R., Singh, S., Sagar, RK, Kumar, R., Sharma, A., Prasad, J., Singh, S., Gurudutta, GU and Sharma, RK (2006b ... Jagetia, GC, Venkatesh, P. and Baliga, MS (2003) Evaluation of the radioprotective effect of Aegle marmelos (L.) Correa in cultured human ...
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Papers by Andreja Leskovac