Iza Ksiazek - Academia.edu (original) (raw)

Papers by Iza Ksiazek

Research paper thumbnail of N-Nitrosodimethylamine Contamination in the Metformin Finished Products

Molecules, 2020

A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitroso... more A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5–9.5 ng/mL. The assay for all substances was accurate and precise. NDMA was not detected in the acquired active pharmaceutical ingredient (API); however, NDMA was detected in 64 (85.3%) and 22 (91.7%) of the finished product and prolonged finished product samples, respectively. European Medicines Agency recommends the maximum allowed limit of 0.032 ppm in the metformin products. Hence, 28 finished products and 7 pronged dosage products were found to exceed the acceptable limit of daily intake of NDMA contamination. The implications of our findings for the testing of pharmaceutical products are discussed.

Research paper thumbnail of Toxicity Studies of Selol-An Organic Selenium (IV) Compound-In Vitro Research

Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation ... more Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation state. Here we present the results of assessing the cytotoxic properties of Selol on BJ and PNT1A normal human cell lines as well as the LNCaP transformed cell line compared to the cytotoxic activity of sodium selenite. Methods: In vitro studies included measuring cell viability using the MTT assay, measuring total protein levels using the Bradford assay as well as measuring pro-apoptotic properties using flow cytometric methods with annexin V and propidium iodide staining. Results: Based on the results of MTT and Bradford assays, the drop in survival of BJ and PNT1A cells under the influence of Selol was low for a wide range of concentrations. There was also no observable pro-apoptotic or necrotic effect of Selol (for Se concentrations of up to approximately 500 μM) on both normal cell lines investigated. There is a marked difference in the levels of cytotoxic activity of Selol between ...

Research paper thumbnail of The influence of an organic selenium (IV) compound on progression of tumour induced using prostate cancer cells and gene expression connected to the oxidative stress response

Analyse the influence of Selol on progression of tumour and the changes in gene expression, conne... more Analyse the influence of Selol on progression of tumour and the changes in gene expression, connected to the cellular oxidative stress response, in cells taken from tumours induced in immunodeficient mice through subcutaneous inoculation with malignant LNCaP prostate cells. Based on the PSA levels (at 5 weeks following inoculation of LNCaP), the mice were divided into three groups. Selol and a placebo were given for the following 3 weeks. After this time, the animals were sacrificed, blood was taken (PSA) and tumours were isolated. RNA from samples was analysed using Real-Time PCR. Treating mice with Selol (21 days at a dose of 17 mg/kg of b.m.) resulted in a drop in the rate of body mass reduction and stopped the increase of plasma PSA levels. The fold changes in expression of the genes, in cells derived from tumours, treated with Selol, in the array, apart from 1 (NME5), failed to exceed the required 2-fold change. Treating tumour-bearing mice with Selol resulted in a reduced rate...

Research paper thumbnail of The influence of Selol on the expression of oxidative stress genes in normal and malignant prostate cells

Cancer genomics & proteomics, 2013

Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil... more Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil, which contain selenium at the +4 oxidation state. The aim of the present study was to describe the changes in the expression of genes related to oxidative stress caused by Selol in prostate cells: both normal (PNT1A) and malignant (LNCaP). The changes in gene expression in PNT1A and LNCaP cell lines under the influence of Selol were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in the cellular oxidative stress response. Based on the obtained data, LNCaP cells exhibited a significantly lower potential for antioxidant defence when compared to PNT1A cells. The response of the malignant LNCaP cells to exposure to Selol was significantly different from that of the normal PNT1A cells, especially after 48 h of incubation. In the case of LNCaP cells, Selol causes down-regulation of the expression...

Research paper thumbnail of Toxicity Studies of Selol - an Organic Selenium (IV) Compound- in Vitro Research

Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation ... more Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation state. Here we present the results of assessing the cytotoxic properties of Selol on BJ and PNT1A normal human cell lines as well as the LNCaP transformed cell line compared to the cytotoxic activity of sodium selenite. Methods: In vitro studies included measuring cell viability using the MTT assay, measuring total protein levels using the Bradford assay as well as measuring pro-apoptotic properties using flow cytometric methods with annexin V and propidium iodide staining. Results: Based on the results of MTT and Bradford assays, the drop in survival of BJ and PNT1A cells under the influence of Selol was low for a wide range of concentrations. There was also no observable pro-apoptotic or necrotic effect of Selol (for Se concentrations of up to approximately 500 μM) on both normal cell lines investigated. There is a marked difference in the levels of cytotoxic activity of Selol between ...

Research paper thumbnail of Case Report of COVID-19 after Full Vaccination: Viral Loads and Anti-SARS-CoV-2 Antibodies

Diagnostics

The introduction of effective vaccines against SARS-CoV-2 is expected to prevent COVID-19. Howeve... more The introduction of effective vaccines against SARS-CoV-2 is expected to prevent COVID-19. However, sporadic cases of infection in vaccinated persons have been reported. We describe a case of a double-dose vaccinated woman with COVID-19. All stages of infection were observed, from no identification of virus, then the start of the infection, a high viral load, coming out of viraemia, and finally no detection of the virus. Despite the high viral load, the woman demonstrated mild COVID-19 symptoms, manifested only by a sore throat. The antibody results showed that she produced both post-infectious and post-vaccination immune responses. Phylogenetic analysis of the obtained viral genome sequence indicated that the virus belonged to the UK SARS-CoV-2 lineage B.1.1.7 (GR 501Y.V1; 20I/S:501Y.V1; Alpha variant).

Research paper thumbnail of Selenized Plant Oil Is an Efficient Source of Selenium for Selenoprotein Biosynthesis in Human Cell Lines

Nutrients

Selenium is an essential trace element which is incorporated in the form of a rare amino acid, th... more Selenium is an essential trace element which is incorporated in the form of a rare amino acid, the selenocysteine, into an important group of proteins, the selenoproteins. Among the twenty-five selenoprotein genes identified to date, several have important cellular functions in antioxidant defense, cell signaling and redox homeostasis. Many selenoproteins are regulated by the availability of selenium which mostly occurs in the form of water-soluble molecules, either organic (selenomethionine, selenocysteine, and selenoproteins) or inorganic (selenate or selenite). Recently, a mixture of selenitriglycerides, obtained by the reaction of selenite with sunflower oil at high temperature, referred to as Selol, was proposed as a novel non-toxic, highly bioavailable and active antioxidant and antineoplastic agent. Free selenite is not present in the final product since the two phases (water soluble and oil) are separated and the residual water-soluble selenite discarded. Here we compare the...

Research paper thumbnail of Comparison of selected gene expression profiles in sensitive and resistant cancer cells treated with doxorubicin and Selol

Contemporary Oncology / Wspólczesna Onkologia

Aim of the study Cellular resistance is strongly correlated with the risk of failure in doxorubic... more Aim of the study Cellular resistance is strongly correlated with the risk of failure in doxorubicin (DOX) treatment, and the knowledge of the mechanisms of resistance and its possible modulation is still very limited. Material and methods In this study, we assessed the effect of 5% Selol and DOX on the expression of genes that affect cell proliferation in the resistant KB-V1 and sensitive HeLa cell lines, using RT2 ProfilerTM PCR Array matrix “Human Cancer Drug Resistance and Metabolism” (SABiosciences). Results We showed that HeLa and KB-V1 cell lines, characterised by varying susceptibility to DOX, have different genetic profiles as regards the studied genes. KB-V1 cells show overexpression of MYC and BCL2 genes, which encode proteins with anti apoptotic properties. Selol, when used in KB-V1 cells, reduced the expression of MYC and BCL2 genes, suggested as a new therapeutic target in the treatment of cancers resistant to cytostatic drugs. Conclusions The results suggest that Selol...

Research paper thumbnail of Selenitetriglycerides—Redox-active agents

Pharmacological Reports, 2015

Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the seco... more Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy. The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice. The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.

Research paper thumbnail of The influence of Selol on the expression of oxidative stress genes in normal and malignant prostate cells

Cancer genomics & proteomics

Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil... more Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil, which contain selenium at the +4 oxidation state. The aim of the present study was to describe the changes in the expression of genes related to oxidative stress caused by Selol in prostate cells: both normal (PNT1A) and malignant (LNCaP). The changes in gene expression in PNT1A and LNCaP cell lines under the influence of Selol were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in the cellular oxidative stress response. Based on the obtained data, LNCaP cells exhibited a significantly lower potential for antioxidant defence when compared to PNT1A cells. The response of the malignant LNCaP cells to exposure to Selol was significantly different from that of the normal PNT1A cells, especially after 48 h of incubation. In the case of LNCaP cells, Selol causes down-regulation of the expression...

Research paper thumbnail of N-Nitrosodimethylamine Contamination in the Metformin Finished Products

Molecules, 2020

A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitroso... more A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5–9.5 ng/mL. The assay for all substances was accurate and precise. NDMA was not detected in the acquired active pharmaceutical ingredient (API); however, NDMA was detected in 64 (85.3%) and 22 (91.7%) of the finished product and prolonged finished product samples, respectively. European Medicines Agency recommends the maximum allowed limit of 0.032 ppm in the metformin products. Hence, 28 finished products and 7 pronged dosage products were found to exceed the acceptable limit of daily intake of NDMA contamination. The implications of our findings for the testing of pharmaceutical products are discussed.

Research paper thumbnail of Toxicity Studies of Selol-An Organic Selenium (IV) Compound-In Vitro Research

Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation ... more Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation state. Here we present the results of assessing the cytotoxic properties of Selol on BJ and PNT1A normal human cell lines as well as the LNCaP transformed cell line compared to the cytotoxic activity of sodium selenite. Methods: In vitro studies included measuring cell viability using the MTT assay, measuring total protein levels using the Bradford assay as well as measuring pro-apoptotic properties using flow cytometric methods with annexin V and propidium iodide staining. Results: Based on the results of MTT and Bradford assays, the drop in survival of BJ and PNT1A cells under the influence of Selol was low for a wide range of concentrations. There was also no observable pro-apoptotic or necrotic effect of Selol (for Se concentrations of up to approximately 500 μM) on both normal cell lines investigated. There is a marked difference in the levels of cytotoxic activity of Selol between ...

Research paper thumbnail of The influence of an organic selenium (IV) compound on progression of tumour induced using prostate cancer cells and gene expression connected to the oxidative stress response

Analyse the influence of Selol on progression of tumour and the changes in gene expression, conne... more Analyse the influence of Selol on progression of tumour and the changes in gene expression, connected to the cellular oxidative stress response, in cells taken from tumours induced in immunodeficient mice through subcutaneous inoculation with malignant LNCaP prostate cells. Based on the PSA levels (at 5 weeks following inoculation of LNCaP), the mice were divided into three groups. Selol and a placebo were given for the following 3 weeks. After this time, the animals were sacrificed, blood was taken (PSA) and tumours were isolated. RNA from samples was analysed using Real-Time PCR. Treating mice with Selol (21 days at a dose of 17 mg/kg of b.m.) resulted in a drop in the rate of body mass reduction and stopped the increase of plasma PSA levels. The fold changes in expression of the genes, in cells derived from tumours, treated with Selol, in the array, apart from 1 (NME5), failed to exceed the required 2-fold change. Treating tumour-bearing mice with Selol resulted in a reduced rate...

Research paper thumbnail of The influence of Selol on the expression of oxidative stress genes in normal and malignant prostate cells

Cancer genomics & proteomics, 2013

Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil... more Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil, which contain selenium at the +4 oxidation state. The aim of the present study was to describe the changes in the expression of genes related to oxidative stress caused by Selol in prostate cells: both normal (PNT1A) and malignant (LNCaP). The changes in gene expression in PNT1A and LNCaP cell lines under the influence of Selol were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in the cellular oxidative stress response. Based on the obtained data, LNCaP cells exhibited a significantly lower potential for antioxidant defence when compared to PNT1A cells. The response of the malignant LNCaP cells to exposure to Selol was significantly different from that of the normal PNT1A cells, especially after 48 h of incubation. In the case of LNCaP cells, Selol causes down-regulation of the expression...

Research paper thumbnail of Toxicity Studies of Selol - an Organic Selenium (IV) Compound- in Vitro Research

Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation ... more Objective: Selol is a mixture of selenitriglycerides, which contain selenium at the +4 oxidation state. Here we present the results of assessing the cytotoxic properties of Selol on BJ and PNT1A normal human cell lines as well as the LNCaP transformed cell line compared to the cytotoxic activity of sodium selenite. Methods: In vitro studies included measuring cell viability using the MTT assay, measuring total protein levels using the Bradford assay as well as measuring pro-apoptotic properties using flow cytometric methods with annexin V and propidium iodide staining. Results: Based on the results of MTT and Bradford assays, the drop in survival of BJ and PNT1A cells under the influence of Selol was low for a wide range of concentrations. There was also no observable pro-apoptotic or necrotic effect of Selol (for Se concentrations of up to approximately 500 μM) on both normal cell lines investigated. There is a marked difference in the levels of cytotoxic activity of Selol between ...

Research paper thumbnail of Case Report of COVID-19 after Full Vaccination: Viral Loads and Anti-SARS-CoV-2 Antibodies

Diagnostics

The introduction of effective vaccines against SARS-CoV-2 is expected to prevent COVID-19. Howeve... more The introduction of effective vaccines against SARS-CoV-2 is expected to prevent COVID-19. However, sporadic cases of infection in vaccinated persons have been reported. We describe a case of a double-dose vaccinated woman with COVID-19. All stages of infection were observed, from no identification of virus, then the start of the infection, a high viral load, coming out of viraemia, and finally no detection of the virus. Despite the high viral load, the woman demonstrated mild COVID-19 symptoms, manifested only by a sore throat. The antibody results showed that she produced both post-infectious and post-vaccination immune responses. Phylogenetic analysis of the obtained viral genome sequence indicated that the virus belonged to the UK SARS-CoV-2 lineage B.1.1.7 (GR 501Y.V1; 20I/S:501Y.V1; Alpha variant).

Research paper thumbnail of Selenized Plant Oil Is an Efficient Source of Selenium for Selenoprotein Biosynthesis in Human Cell Lines

Nutrients

Selenium is an essential trace element which is incorporated in the form of a rare amino acid, th... more Selenium is an essential trace element which is incorporated in the form of a rare amino acid, the selenocysteine, into an important group of proteins, the selenoproteins. Among the twenty-five selenoprotein genes identified to date, several have important cellular functions in antioxidant defense, cell signaling and redox homeostasis. Many selenoproteins are regulated by the availability of selenium which mostly occurs in the form of water-soluble molecules, either organic (selenomethionine, selenocysteine, and selenoproteins) or inorganic (selenate or selenite). Recently, a mixture of selenitriglycerides, obtained by the reaction of selenite with sunflower oil at high temperature, referred to as Selol, was proposed as a novel non-toxic, highly bioavailable and active antioxidant and antineoplastic agent. Free selenite is not present in the final product since the two phases (water soluble and oil) are separated and the residual water-soluble selenite discarded. Here we compare the...

Research paper thumbnail of Comparison of selected gene expression profiles in sensitive and resistant cancer cells treated with doxorubicin and Selol

Contemporary Oncology / Wspólczesna Onkologia

Aim of the study Cellular resistance is strongly correlated with the risk of failure in doxorubic... more Aim of the study Cellular resistance is strongly correlated with the risk of failure in doxorubicin (DOX) treatment, and the knowledge of the mechanisms of resistance and its possible modulation is still very limited. Material and methods In this study, we assessed the effect of 5% Selol and DOX on the expression of genes that affect cell proliferation in the resistant KB-V1 and sensitive HeLa cell lines, using RT2 ProfilerTM PCR Array matrix “Human Cancer Drug Resistance and Metabolism” (SABiosciences). Results We showed that HeLa and KB-V1 cell lines, characterised by varying susceptibility to DOX, have different genetic profiles as regards the studied genes. KB-V1 cells show overexpression of MYC and BCL2 genes, which encode proteins with anti apoptotic properties. Selol, when used in KB-V1 cells, reduced the expression of MYC and BCL2 genes, suggested as a new therapeutic target in the treatment of cancers resistant to cytostatic drugs. Conclusions The results suggest that Selol...

Research paper thumbnail of Selenitetriglycerides—Redox-active agents

Pharmacological Reports, 2015

Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the seco... more Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy. The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice. The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.

Research paper thumbnail of The influence of Selol on the expression of oxidative stress genes in normal and malignant prostate cells

Cancer genomics & proteomics

Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil... more Selol is a mixture of selenitriglycerides, obtained by the chemical modification of sunflower oil, which contain selenium at the +4 oxidation state. The aim of the present study was to describe the changes in the expression of genes related to oxidative stress caused by Selol in prostate cells: both normal (PNT1A) and malignant (LNCaP). The changes in gene expression in PNT1A and LNCaP cell lines under the influence of Selol were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in the cellular oxidative stress response. Based on the obtained data, LNCaP cells exhibited a significantly lower potential for antioxidant defence when compared to PNT1A cells. The response of the malignant LNCaP cells to exposure to Selol was significantly different from that of the normal PNT1A cells, especially after 48 h of incubation. In the case of LNCaP cells, Selol causes down-regulation of the expression...