Publications by authors named "Katarzyna Malinowska"

53 Publications

[Development and validation of method for the determination of cynarin, luteolin in plasma].

Przegl Lek 2012 ;69(10):987-91

Laboratorium Badań Srodowiskowych, Katedra i Zakład Toksykologii, Uniwersytet Medyczny im. Karola Marcinkowskiego, Poznań.

The aim of this study was to develop and validate the method of cynarin and luteolin, the main constituents of artichoke (Cynara scolymus L.) leaf extract, determination in plasma. The compounds were separated using the high-performance liquid chromatography technique with diode array detection (HPLC-DAD). The analysis was preceded by liquid-liquid extraction using as the extracting agent ethyl acetate. The HPLC separation was performed on C18 column under gradient conditions using a mobile phase - 0,05% trifluoroacetic acid in water and methanol. The detector was set at lambda=330 nm. The validation was related to linearity, sensitivity (LOD and LOQ), accuracy and repeatability. In the validated method the linearity was achieved within concentration range 1,5625 - 50,0 microg/cm3 for the cynarin (R2=0,9989) and 1,5625 - 200,0 microg/cm3 for the luteolin (R2=0998). The limits of detection for cynarin and luteolin was: 0,75 microg/cm3 and 0,1 microg/cm3 and the limits of quatification: 2,25 microg/cm3 and 0,2 microg/cm3, respectively. Coefficient of variation for the inter-day and the intra-day analysis, which is a precision and accuracy parameter, do not exceed 10%. Recovery was 67% for the cynarin and 96% for the luteolin. The practical application of this method was proved by analysis of plasma samples from rats. The animals were administrated artichoke leaf extract - orally and intraperitoneally at a dose of 3 g/kg body weight or pure substances - intraperitoneally at a dose 1 mg/kg of luteolin and 0,5 mg/kg of cynarin. The presence of investigated compounds was proved only in samples after intraperitoneal administration of pure substances. The developed method is used to determine simultaneously cynarin and luteolin, after intraperitoneal administration of pure compounds.
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April 2013

Effect of Cu(II) coordination compounds on the activity of antioxidant enzymes catalase and superoxide dismutase in patients with colorectal cancer.

Pol Przegl Chir 2011 Mar;83(3):155-60

Department of Chemistry and Clinical Biochemistry, Medical University in Łódź.

Unlabelled: Colorectal cancer (CRC) is a serious medical and economical problem of our times. It is the most common gastrointestinal cancer in the world. In Poland, the treatment and detection of CRC are poorly developed and the pathogenesis is still unclear. One hypothesis suggests a role of reactive oxygen species (ROS) in the pathogenesis of CRC. Experimental studies in recent years confirm the participation of ROS in the initiation and promotion of CRC. The aim of the study was to examine the effect of the following coordination compounds coordination compounds: dinitrate (V) tetra(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(3,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dinitrate (V) di(1,4,5-trimethyl-N1-pyrazole-κN2) copper(II), dichloro di(1,3,4,5-tetramethyl-N1-pyrazole-κN2) copper(II) on the activity of antioxidant enzymes superoxide dismutase (SOD, ZnCu-SOD) and catalase (CAT) in a group of patients with colorectal cancer (CRC) and in the control group consisting of patients with minor gastrointestinal complaints.

Material And Methods: The study was conducted in 20 patients diagnosed with colorectal cancer at the age of 66.5±10.2 years (10 men and 10 women) versus the control group of 20 people (10 men and 10 women) aged 57.89±17.10 years without cancer lesions in the biological material - hemolysate prepared in a proportion of 1ml of water per 1 ml of blood. CAT activity was measured by the Beers method (1952), while SOD activity was measured by the Misra and Fridovich method (1972).

Results: We found that patients with CRC showed a statistically significant decrease of SOD and CAT activity (CAT - 12,75±1.97 U/g Hb, SOD - 1111.52±155.52 U/g Hb) in comparison with the control group (CAT - 19.65±2,17 U/g Hb, SOD - 2046.26±507.22 U/g Hb). Simultaneously, we observed that the investigated coordination compounds of Cu(II) significantly increased the antioxidant activity of CAT and SOD in patients with CRC (mean: CAT 25.23±4.86 U/g Hb, SOD - 3075.96±940.20 U/g Hb).

Conclusions: Patients with colorectal cancer are characterized by reduced activity of antioxidant enzymes catalase and superoxide dismutase which suggests impaired antioxidant barrier. Therefore, coordination compounds of Cu (II), which enhance the activity of CAT and SOD, may prove useful in the prevention and treatment of colorectal cancer.
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http://dx.doi.org/10.2478/v10035-011-0024-6DOI Listing
March 2011

[The effects of whole-body cryotherapy and melatonin supplementation on total antioxidative status and some antioxidative enzymes in multiple sclerosis patients].

Pol Merkur Lekarski 2011 Sep;31(183):150-3

Neurorehabilitation Ward, III Municipal Hospital in Łódź, Poland.

Unlabelled: Oxidative stress is an important factor which contribute to the pathogenesis of lesions in multiple sclerosis (MS). Whole body cryotherapy (WBCT) is often used in treatment neurological and orthopedic diseases.

The Aim, Material And Methods: The aim of this study was to determinate the level of total antioxidative status (TAS) in plasma and activity of superoxide dismutase (SOD) and catalase (CAT) in erythrocytes of MS patients (n = 28) before and after 10 exposures of WBCT (-120 degrees C/3 minutes/day). 16 MS patients during 10 exposures of WBCT additionally were supplemented by 10 mg of melatonin.

Results: Increasing of TAS level in plasma as well as supplemented with melatonin and non-supplemented MS patients was observed after 10 exposures of WBCT Melatonin statistically significant increased activity of SOD and CAT in erythrocytes of MS patients treated with WBCT.

Conclusions: Results of our study indicate significant increase of TAS level in plasma of MS patients of WBCT treatment. This indicate that WBCT might be a therapy which suppress oxidative stress in MS patients.
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September 2011

Evaluation of oxidative stress markers in pathogenesis of primary open-angle glaucoma.

Exp Mol Pathol 2011 Apr 15;90(2):231-7. Epub 2011 Jan 15.

Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland.

Primary open-angle glaucoma (POAG) is the leading cause of blindness in the industrial countries. It is reported that oxidative stress might be an important risk factor in the pathogenesis of POAG. Forty subjects including 20 patients with open-angle glaucoma (9 men and 12 women, mean age 61.8±12.1yr) and 20 controls without glaucoma symptoms (9 men and 12 women, mean age 58.1±17.7yr) were enrolled in our study. The main aim of the work was to evaluate oxidative stress markers in the pathogenesis of open-angle glaucoma. In our work the activity of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as the total antioxidant status (TAS) was estimated. An alkaline comet assay was used to measure DNA damage of strand breaks (SB), oxidized purines as glicosylo-formamido-glicosylase (Fpg) sites, and oxidized pirmidines as endonuclease III (Nth) sites. We measured endogenous as well as exogenous DNA damage after 10μM hydrogen peroxide treatment (H(2)O(2)). We did not observe any statistical changes of DNA strand break lesion in examined POAG patients according to healthy subjects (P>0.05). However, either endogenous (P<0.01) or exogenous (P<0.001) levels of oxidative DNA damage in POAG patients were found to be statistically higher than controls. A significant decrease of antioxidant enzymes: CAT (P<0.001), SOD (P<0.05), and GPX (P<0.001) and a non-statistical decrease of TAS status (P>0.05) in glaucoma patients according to controls were also indicated. In conclusion our data revealed that oxidative stress had a pathogenic role in primary open-angle glaucoma. Therefore, we suggested that the modulation of a pro-oxidant/antioxidant status might be a relevant target for glaucoma prevention and therapy.
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http://dx.doi.org/10.1016/j.yexmp.2011.01.001DOI Listing
April 2011

Effects of whole-body cryotherapy on a total antioxidative status and activities of antioxidative enzymes in blood of depressive multiple sclerosis patients.

World J Biol Psychiatry 2011 Apr 18;12(3):223-7. Epub 2010 Nov 18.

Neurorehabilitation Ward, III General Hospital Lodz, Lodz, Poland.

Objectives: Oxidative stress (OS) plays an important role in the pathogenesis of multiple sclerosis (MS). In MS patients depression is often observed. Cryotherapy might have an effect on OS. The aim of this study was to compare the effects of whole body cryotherapy (WBCT) on changes in total antioxidative status (TAS) of plasma and activities of antioxidative enzymes in erythrocytes from depressive and non depressive MS patients.

Methods: Twenty-two MS patients with secondary progressive disease course (12 depressive and 10 non depressive) were treated with 10 exposures in a cryochamber. Before and after WBCT the plasma TAS and the activities of superoxide dismutase (SOD) and catalase (CAT) in the erythrocytes were measured.

Results: The level of TAS in depressive MS group was significantly lower than in non depressive MS (P < 0.0003). WBCT increased the level of TAS in depressive (P < 0.002) more than in non depressive MS patients (P < 0.01). WBCT treatment of MS patients resulted in the significant increase of TAS level in plasma but had no effects on activities of SOD and CAT.

Conclusions: Our results indicate that WBCT suppresses OS in MS patients, especially in depressive patients.
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http://dx.doi.org/10.3109/15622975.2010.518626DOI Listing
April 2011

[Etiology of colorectal cancer and antioxidant barrier of the organism].

Pol Merkur Lekarski 2010 Mar;28(165):223-6

Uniwersytet Medyczny w Łodzi, Wydział Fizjoterapii, III Katedra Rehabilitacji, Zakład Historii Nauk i Medycyny Wojskowej.

Colorectal cancer is a serious medical and economic problem in Poland, as the detection and results of its treatment are very low. Due to this fact, medical research is still conducted in order to find out the symptoms of this tumor and proper preventive measures. According to one hypothesis of carcinogenesis, the process of creating the tumor begins and develops when the balance between the production of reactive oxygen species (ROS) and their deactivation by the "antioxidant protective barrier of the organism" is disturbed. As a result of this theory, it has been decided to examine the plasma concentration of the dietary minerals which work as antioxidants. The results entailed conclusions which prove the free radicals theory of carcinogenesis. They also confirm the part which the antioxidant protective barrier plays in the defence against ROS and their carcinogenic consequences.
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March 2010

[Effect of melatonin on activity of superoxide dismutase (CuZn-SOD) in erythrocytes of patients during short- and long-term hypokinesis].

Wiad Lek 2010 ;63(1):3-9

Zakład Chemii i Biochemii Klinicznej Uniwersytetu Medycznego w Łodzi.

Introduction: Short- or long-lasting hypokinesis is to a large degree the consequence of negative habits of human beings towards a comfortable and more sedentary lifestyle. The period of decreased physical activity can cause disturbance in the balance between systemic processes of the oxidation and reduction, which leads to an increase in reactive oxygen species (ROS) and oxidative stress generation. The aim of the study was to determine the effect of melatonin administration on the cellular superoxide dismutase (CuZn-SOD) activity in red blood cells of patients with short- and long-term hypokinesis as compared to the group of subjects with normal physical activity.

Material And Methods: The study included 33 subjects with immobilization. The study group was divided into two subgroups (depending on hypokinesis duration): group A: 15 subjects classified for total hip alloplasty (a short-lasting decrease in physical activity); group B: 18 subjects suffering from multiple sclerosis or the stroke of brain (the long-term hypokinesis). The control group (group C) comprised 17 subjects with normal physical activity. Melatonin was applied at a dose of 5 mg daily, one hour before sleep. The CuZn-SOD activity in red blood cells was determined, according to the Misra and Fridovich method, in two periods: 1) on the first day, 2) on the 10th day (group A), and 30 days (group B) after melatonin administration.

Results: A slight increase in CuZn-SOD activity (+3.1%) was observed in group A 10 days after alloplasty and melatonin administration as compared to group B, where a considerable rise in the enzyme activity (+23.3%) was found 30 days after rehabilitation and melatonin supplementation. The average CuZn-SOD activity in both investigative groups was lower than that in the controls (group C).

Conclusions: It was estimated that the short- and long-lasting hypokinesis leads to an increase in ROS generation, what is confirmed by the increase in CuZn-SOD activity. The results of the study on superoxide dismutase activity indicate that oral administration of melatonin for the period of 30 days has a more favorable influence on antioxidative processes than 10-day's melatonin intake.
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November 2010

[Influence of chromone compounds on the activity of selected antioxidant enzymes in patients with physical limitations].

Pol Merkur Lekarski 2010 Jan;28(163):26-8

Uniwersytet Medyczny w Łodzi: Wydzial Fizjoterapii, Zakład Chemii i Biochemii Klinicznej, Katedra Chemii i Biochemii Klinicznej.

Unlabelled: Coxarthrosis used to be referred to as the "doctors' cross" pointing to the difficulties of the treatment. Degenerative processes in the bones usually concern large joints: knee joints in 25-40% of cases, similarly in case of hip joints. Because of the role the joints play, the arthrosis may result in physical limitations or disability. The aim of the study was to evaluate the activity of catalase and superoxide dismutase (CuZn-SOD) in erythrocytes in patients suffering from the coxarthrosis--as the studied group and in healthy people--as the control group.

Materials And Methods: Determining the activity of catalase and superoxide dismutase in the group of 17 patients hospitalized because of coxarthrosis.

Results: In the study about 90% increase of the activity of the enzymes was determined in the studied group, in which the chemical compound 3{(2-aminothiazolyl)methylene}4H-1-benzopyran-4-one was added to the blood, in comparison with the control group.

Conclusion: The results of the test on catalase and superoxide dismutase clearly indicate that the free radicals participate in the whole course of coxarthrosis.
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January 2010

[Influence of copper (II) complex on the activity of selected oxidative enzymes].

Pol Merkur Lekarski 2010 Jan;28(163):22-5

Uniwersytet Medyczny w Łodzi: Wydzial Fizjoterapii, Zakład Chemii i Biochemii Klinicznej, Katedra Biomedycznych Podstaw Fizjoterapii.

Unlabelled: Coxarthrosis results in physical limitations (hypokinesis) and a necessity to change one's life style to the one that does not require much movement. Physical inactivity leads rapidly to metabolic processes inhibition. The processes of protein, carbohydrate and lipid catabolism intensify. Abnormal metabolism of polyunsaturated fatty acids occurs, which consequently leads to the development of reactive oxygen species (ROS) and to the acceleration of lipid peroxidation. Therefore, it is well-founded to seek for a new group of compounds demonstrating interesting biochemical properties. Among such already known compounds are chromone, azole and flavone derivatives, known for their oxidative properties. The aim of the study was to assess the antioxidant enzymes: catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes in 25 patients suffering from coxarthrosis in comparison with healthy persons.

Materials And Methods: The activity of catalase was determined in erythrocytes using the method of Beers and Sizer at 240 nm on the Beckman spectrophotometer. The activity of glutathione peroxidase was estimated using the method of Little and O'Brien at 412 nm on the Beckman spectrophotometer. The research was conducted with the permit of the Bioethics Committee No RNN/260/08/KB dated 20.05.2008. Blood for the tests was taken from periulnar vein to anticoagulant tubes (EDTA). The group consisted of 25 patients hospitalized in the Trauma and Orthopaedic Ward of the Hospital in Łódź.

Results: The results of the tests on erythrocytes in the patients with physical limitations reveal the increase of glutathione peroxidase and catalase activity by about 50% in all patients, who were administered the dichlorobis (N1-dichloromethyl-3,5-dimethylpyrazole, copper (II) compound in comparison to the control group, where the foregoing compound was not used.

Conclusion: The research results significantly emphasise that adding of new chemical compounds to blood in investigation of oxidative properties has a considerable influence on the activity of the selected enzymes (catalase and glutathione peroxidase) in comparison to the control group. The research reveals an increase of the activity of all antioxidant enzymes, where newly synthesized chemical compounds were used. The results of antioxidative capacity tests confirmed that complex compounds with Cu (II) ions have a significant influence on the antioxidative status. The studies on the foregoing enzymes also indicate that overproduced free radicals participate in the whole course of the coxarthrosis.
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January 2010

Effects of the whole-body cryotherapy on a total antioxidative status and activities of some antioxidative enzymes in blood of patients with multiple sclerosis-preliminary study.

J Med Invest 2010 Feb;57(1-2):168-73

Rehabilitation Ward, III General Hospital in Lódz, Poland.

Objective: There is evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. Neutralization of oxidative stress and excitotoxicity, might represent a therapeutic approach to provide neuroprotection in MS. The purpose of this study was to compare changes in total antioxidative status and activities of chosen antioxidative enzymes, such as: SOD, CAT in erythrocytes of patients with MS before and after using WBCT with control group.

Materials And Methods: 32 patients with multiple sclerosis (ICD10-G35) and 20 healthy subjects were recruited for the study. The examined MS group (n=16) was treated with a series of 10 daily exposures in a cryogenic chamber (2-3 min, from -120 degrees C to -110 degrees C) and program of exercises. The control MS group (n=16) had only exercises. Plasma TAS as well as SOD and CAT activities in erythrocytes were measured.

Results: The level of TAS in MS patients was distinctly reduced compared to healthy subjects. After two weeks of WBCT treatment an increase of TAS in the whole examined group (p>0.01) were observed in relation to control MS group. There was not increase of CuZnSOD and CAT activities.

Conclusion: Our results suggest positive antioxidant effects of WBCT as a short-term adjuvant treatment for patients suffered due to MS.
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http://dx.doi.org/10.2152/jmi.57.168DOI Listing
February 2010

[Activity of selected antioxidant enzymes examination in people with colorectal cancer].

Pol Merkur Lekarski 2009 Dec;27(162):470-3

Uniwersytet Medyczny w Łodzi, Wydział Fizjoterapii, III Katedra Rehabilitacji, Zakład Historii Nauk i Medycyny Wojskowej.

Unlabelled: Colorectal cancer is a serious medical problem. According to one hypothesis of carcinogenesis, tumour creation process begins and develops when the balance between the production of reactive oxygen species (ROS) and their disactivation by the antioxidant protective barrier of the organism is disturbed. THE AIM OF THE STUDY was, following this theory, to examine the plasma concentration of the dietary minerals with antioxidant properties.

Material And Methods: The research material was the blood of 8 people, taken to vacuum test tubes with an anticoagulant - 4 ml of sodium heparin. The activity of catalase was marked following Beers method, while the activity of superoxide dismutase according to H.P. Misra and J. Fridovich method.

Results: The results show that the copper complex added, i.e. dichlorine(3,4,5-trimethyl-N1 - pyrazol-1yl) Cu(II) from derivatives of azoles, has a large impact on the activity of selected enzymes. After adding it, their activity increased by ca 67% in comparison with the control group. It proves the efficacy of this compound.

Conclusions: The results prove the free radicals theory of carcinogenesis. They also confirm the part which the antioxidant protective barrier plays in the defense against ROS and their carcinogenic consequences.
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December 2009

[Influence of complex compounds on the activity of antioxidant enzymes in neoplastic diseases of the digestive tract].

Pol Merkur Lekarski 2009 Aug;27(158):97-100

Medical University of Łódź, The Faculty of Physiotherapy, Department of Chemistry and Clinical Biochemistry, Poland.

Unlabelled: Chemotherapy is an important field of clinical medicine and pharmacology Chemotherapy is the main method of treating the neoplasm. It involves treating the neoplastic disease with the use of natural or synthetic anticancer drugs commonly known as the cytostatics. The cancer therapy involving the cytostatics is a difficult and not always effective process, which requires taking into consideration the mechanisms of action, pharmacokinetics and the dosage schemas. The complexity of the chemotherapy is influenced by: still incomplete knowledge of causes of neoplasm formation, slight biological differences between the cancer cells and the regular cells, very small selectivity of cytostatics' action, narrow therapeutic index of the anticancer drugs, high toxicity for healthy cells and unsatisfactory anticancer activity. The aim of the study was to obtain the complex compounds of copper (II), and especially of dinitrate (V) di (3,4, 5-trimethyl-N1-pyrazol-kappaN2) copper (II), and its subsequent testing for pro- and antioxidative activity in people suffering from neoplastic diseases of the digestive tract (colorectal and gastric carcinoma). Material and methods. The activity of catalase was determined in erythrocytes patients suffering from colorectal and gastric carcinoma and in control group (hernia, chronic gastric ulcer disease and haemorrhoids) using the method of Beers and Sizer at 240 nm on the Beckman spectrophotometer.

Results: The results of the test on catalase in patients suffering from colorectal and gastric carcinoma indicate that the addition to the blood of the complex compound of Cu(II) significantly influences the activity of the enzyme in comparison with the control group in which the substance tested was not used. In the tests a marked statistical difference was observed between the studied and the control group.

Conclusion: The results reveal that chemical compounds, that is, dinitrate (V) di (3,4,5-trimethyl-N1-pyrazol-kappaN2) copper (II), has a significant influence on the activity of catalase, the antioxidant enzyme.
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August 2009

[Tumour illnesses and nutrition].

Pol Merkur Lekarski 2009 Sep;27(159):242-4

Medical University of Lodz, Faculty of Physiotherapy, Department of History of Sciences and Military Medicine, Poland.

It is very important for contemporary medicine to create new effective cytotoxic compounds of platinum with better clinical tolerance. Harmful elements which exist in food delivered to a human organism may either get inactive or activate complex processes which may to lead to illnesses such as tumors. One of these elements are. Undoubtedly, free radicals. They destroy, among other things, the DNA, causing changes in the genetic code and its mutations. More recently came the publication of speaking a lot about the capabilities of the organism to defend against the above-mentioned factors. Eating adequate amounts of fruits and vegetables contain antioxidants in its composition contributes positively to our body and reduces the risk of cancer.
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September 2009

[Total antioxidant status concentration in blood plasma of professional sportsmen after dosed physical exercise].

Pol Merkur Lekarski 2009 Jul;27(157):22-5

Uniwersytet Medyczny w Łodzi, Wydział Fizjoterapii, Katedra i Zakład Chemii i Biochemii Klinicznej.

Unlabelled: The mechanism of functioning of the well-balanced protection system against free radicals is based on the mutual and synergistic activity of its all elements. One of the first organism reactions to physical effort is an elevated oxygen requirement due to an increased rate of metabolism, particularly in the skeletal muscles involved in performing physical work. In case of insufficient antioxidative system of blood plasma, free radicals attack the erythrocytic membrane externally and internally, leading to formation of considerable amounts of reactive oxygen species (ROS). The aim of this study was to evaluate the influence of dosed submaximal and maximal physical exercise on the plasma total antioxidant status (TAS) concentration in professional sportsmen and in subjects of normal physical activity.

Material And Methods: 41 rugby players (junior and senior group) and 20 men of normal physical activity (control group) were the subject of the study. The plasma TAS concentration was determined: before an effort in the control group, and after 30-minute restitution period in sportsmen.

Results: The concentration of TAS values in subjects of normal physical activity before exercises were on average 0.65 +/- 0.15 mmol/l. In the junior group after the dosed submaximal physical exercise, the mean TAS concentration was 0.69 +/- 0.29 mmol/l, but the dosed maximal exercise lead to an increase in TAS values - 0.73 +/- 0.34 mmol/l. The higher plasma TAS concentration after the dosed submaximal physical exercise was observed in the senior group as compared to the junior group, and was on average 0.93 +/- 0.22 mmol/l. However, after the maximal exercise, the TAS concentration decreased and its average value was 0.66 +/- 0.26 mmol/l.

Conclusions: The results of the study indicate that the intensity of performed exercises affects the plasma TAS concentration during a single physical activity. The plasma TAS concentration was higher in sportsmen regardless of the type of effort as compared to the control group. Supplementation of micromolecular antioxidants present in nutrients ingested by the sportsmen might have influenced the study outcomes.
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July 2009

[Testing antineoplastic activity of new platinum(II) and palladium(II) complex compounds].

Pol Merkur Lekarski 2009 Jan;26(151):57-61

Uniwersytet Medyczny w Lodzi, Wydział Fizjoterapii, Zakład Chemii i Biochemii Klinicznej, Katedra Chemii i Biochemii Klinicznej.

Unlabelled: A pyrazole system is incorporated in many biological molecules which play an important part in genetic processes. It seems that co-ordinating biological molecules, which would serve as carriers, should contribute to minimising the toxic effects of the potential platinic drugs.

Aim Of The Study: Assessment of in vivo biological activity, and in particular of antineoplastic activity of new platinum(II) and palladium(II) complexes.

Material And Methods: The assessment of toxicity of the compounds was made with the Deichmann and Le Blanck method. The antineoplastic activity of the new complex compounds--pyrazole derivatives with Pt(II) and Pd(II) ions was tested on mouse L1210 leukemia cell culture and on lymphatic leukemia P388. BDF1 or CDF1 mice divided into groups of 5-9 animals were subject to the tests.

Results: Complexes 13, 21, 25, 16, 24 and 28 did not reveal any antineoplastic activity to the mouse L1210 leukemia, whereas complexes 13, 21 and 25 revealed in-vivo antineoplastic activity to the P388 leukemia, extending the mouse's survival time by about 50%. The control group consisted of mice which were administered a 14% methylcellulose solution.

Conclusions: As a result of the tests conducted to asses the in-vivo antineoplastic activity it was found that the 25 complex demonstrates the strongest activity to the P388 leukemia. It may be presumed that it is caused by trans configuration of the complex predisposing to the creation of interstrand cross-links. It may be also caused by the presence of the chloromethyl substituents, located on N1 nitrogen atom of the ligand, which increases the capacity of nitrogen N7 guanine alkylation in DNA.
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January 2009

[In vitro biological activity of new platinum(II) and palladium(II) complex compounds].

Pol Merkur Lekarski 2009 Jan;26(151):52-6

Uniwersytet Medyczny w Lodzi, Wydział Fizjoterapii, Zakład Chemii i Biochemii Klinicznej, Katedra Chemii i Biochemii Klinicznej.

Unlabelled: A nitrogen ring is present in many biological molecules, which play an important part in cell division as well as in genetic information transfer. It is also a part of the purine system, which builds DNA and has potential places/spots of platinum drug co-ordination. Therefore, it may be hoped, that platinum(II) complexes with diazol ligands will have considerable affinity for DNA binding sites. The work was aimed at assessment of biological activity and especially of cytotoxic activity, of new complex connections of the selected diazols with Pt(II) and Pd(II) ions.

Materials And Methods: The MTT test is aimed at the assessment of cytotoxicity of chemical compounds. It consists in the colorimetric determination of a product--farmazon, formed after adding MTT (bromide 3[4,5-dimetylo-2-ilo]-2,5-difenylotetrazolu) to the culture suspension in the presence of the compound subject to the test. All the tested Pt(II) complexes before adding to the cell cultures were dilluted in DMF. MTT tests for individual complexes were conducted on two cell lines L1210 and P388.

Results: Compounds 13, 21 and 25 on P388 neoplastic cell revealed about three times smaller in-vitro cytotoxicity, whereas platinum(II) and palladium(II) complexes 13, 21, 25, 43, 46, revealed cytotoxicity being about 3-4 times smaller than the reference cisplatin. Complex 45 revealed eight times smaller activity and complex 44 revealed significantly small, about two hundred smaller activity.

Conclusion: Based on the MTT tests it may be concluded that compounds 13, 21 and 25 reveal selective cytotoxicity to P388 neoplastic cells.
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January 2009

[Chosen non-enzymatic substances that participate in a protection against overproduction of free radicals].

Pol Merkur Lekarski 2008 Sep;25(147):269-72

Uniwersytet Medyczny w Łodzi, Zaktad Chemii i Biochemii Klinicznej.

Free radicals are substantial elements that take part in proper function of metabolic pathways of human cells and tissues in hydrophobic as well as in hydrophilic environment. Nevertheless overproduction of above molecules causes oxidative stress, a process which is very harmful for lipids, proteins, and others molecules what reduces their normal function. To protect against adverse effects of free radicals and theirs derivatives to human body there is a group of antioxidants divided into enzymatic and non-enzymatic substances. Enzymatic antioxidants are represented mainly by enzymes such as: copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). Glutathione (GSH), thioredoxin (Trx), vitamins, melatonin, polyphenols, trace elements, albumin, and others function as non-enzymatic free radicals scavengers. This work in a brief way describes properties of chosen representants of non-enzymatic antioxidant system.
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September 2008

[Role of flavonoids as antioxidants in human organism].

Pol Merkur Lekarski 2008 Jun;24(144):556-60

III Szpital Miejski w Lodzi, Oddział i Poradnia Rehabilitacji.

The increasing interest in flavonoids means higher demand for the complex and synthetic knowledge about those substances. The following study is an overview of the contemporary knowledge about the mentioned substances, and hopefully it will magnify this topic. Flavonoids are the ingredients of many nutrition substances and a vital diet element. They are also a group of many medicines with different influence on live organisms. At the moment, there are over hundreds of bio-flavonoids identified. The phenol compounds are used as natural drugs in the cases of various sicknesses of blood, breathing, food, and urinary circuit, and in dermatology as well. The existence of these compounds in the diet, especially maintenance of their proper consumption level, is a very important element in the prevention of many diseases, such as atherosclerosis. The intensity of experimental studies on flavonoids in the last decade (mainly studies on cell cultures) showed varied attributes of these compounds. The results give hope for the use of flavonoids in prevention and neoplasmatic treatment. Phenol compounds as antioxidants may affect in many different aspects: direct reaction with free radicals, scavenging free radicals, growing dismutation of free radicals to the compounds with much lower reactiveness, chelatation of pro-oxidant metals (mainly iron), delaying or strengthening many enzymes. What is more, they can strengthen the functionality of other antioxidants, such as vitamins resolving in fat, and low-molecular substances resolving in water. The wide spectrum of the functions of flavonoids and their synthetic derivatives gives hope for the research of new chemical compounds (drugs) with exploratory characteristics.
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June 2008

[Role of free radicals in the physiological processes].

Pol Merkur Lekarski 2008 May;24(143):446-8

Medical University of Lódź, Department of Clinical Chemistry and Biochemistry, Poland.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced during variety of biological processes. Low concentration of these molecules influences cell growth, differentiation or proliferation. Above derivatives of oxygen and nitrogen take part in physiological processes such as signal transduction, regulation of protein kinases or transcription factors. ROS and RNS regulate redox balance, regulate immune responses, activate macrophages and neutrophils. Under theirs' control is cell adhesion and relaxation of smooth muscles. These molecules are very important for correct function and life of the cell.
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May 2008

[Derivatives pyrazoles used in a medical treatment].

Pol Merkur Lekarski 2008 Feb;24(140):151-7

Uniwersytet Medyczny w Łodzi, Wydział Fizjoterapii, Katedra Chemii i Biochemii Klinicznej, Zakład Chemii i Biochemii Klinicznej.

Contemporary coordinative chemistry is still searching new substances that might constitute good ligands for transient metal ions: Cu(II), Ni(II), Co(II), Pt(II), Pd(II) oraz Cr(III). Pyrazole and its derivatives are able to make complexes with transient metal ions. There is a connection between pharmacological and chemical structure among pyrazole derivatives used in a medical treatment. A chemical division is coincident with a pharmacological division. Pyrazole-5 derivatives are mainly analgesic, antipyretic and less anti-inflammatory and diastolic but pyrazolidyn-3.5-dion derivatives are anti-inflammatory. The main part of non-steroid anti-inflammatory drugs belonging to pyrazolone derivates has a phenyl group at the first position. The activity and toxicity of this drugs are dependent on groups being at the fourth position. For example, the dimethylamino group makes aminophenazon antianalgetic, and yet is also responsible for a big toxicity. Azole derivatives are antimycotic and are ingredients of some ointments and creams. Chemical groups at the fourth position may determine the activity and the toxicity. These days a great attention is paid on a synthesis which is linking pyrazole and ions of platinum Pt(II) and palladium Pd(III) due to anticancer properties but pharmacology is not known very well.
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February 2008

[Calcium ions, glutaminate acid, hypothalamic-pituitary-adrenal axis, calcium dependent ATP-ase as causes of oxidative damage in depression patients--Part I].

Pol Merkur Lekarski 2007 Dec;23(138):466-8

Uniwersytet Medyczny w Lodzi, Klinika Psychiatrii Dorosłych.

Depressive disorder is still a rising and important problem in the modem world, it affects about 15% of the population. Present forms of treatment are effective in about 70% and require monthly therapy which sometimes causes side effects. Last decade studies paid attention to theories different to monoaminergic and to neurodegenerative changes mainly in the limbic system of hippocampus. In this article authors show a relationship between calcium ions, glutaminergic transduction and disfunction of hypothalamic-pituitary-adrenal (HPA) axis. They also take into account the activity of calcium dependent ATPase and its influence on overproduction of reactive oxygen species in the central neuron system (CNS). The first part of this article proves that disregulation of HPA increases the glutaminergic conduction in neurons and causes a cytoskeletal damage in the CNS.
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December 2007

[Anticancer drugs used in medicine and being in clinical research].

Pol Merkur Lekarski 2007 Sep;23(135):165-9

Tumor diseases are most serious issue of clinical medicine and pharmacology. The coordination compounds of platinum (II) are fundamental group of drugs used in antineoplastic therapy and cisplatin is the first antitumor specimen used in health care. Cisplatin is used in treatment for e.g. ovarian carcinoma, microcellular and no microcellular pulmonary carcinoma, orchiencephaloma, neck and esophagus carcinoma. Carboplatin is the second specimen applied in tumors' therapy. Both the coordination compound of platinum (II) possesses similar antineoplastic action but have a different effectiveness of activity and toxicity. It's very important for contemporary medicine to create new effective cytotoxic compounds of platinum with better clinical tolerance.
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September 2007

Comparative studies on the mechanism of cytotoxic action of novel platinum II complexes with pyrazole ligands.

J Inorg Biochem 2006 Oct 23;100(10):1579-85. Epub 2006 May 23.

Department of Molecular Pharmacology, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.

In search for new platinum-based anticancer drugs, four cisplatin analogues, which contain pyrazole rings as non-leaving ligands, have been synthesized: cis-PtCl(2)(3,5-DM HMPz)(2), cis-PtCl(2)(Pz)(2), cis-PtCl(2)(ClMPz)(2), and cis-PtCl(2)(HMPz)(2), where Pz=pyrazole, H=hydroxyl, M=methyl. We tested their cytotoxicity, apoptosis induction ability, DNA damaging and modification properties comparing them in respect to the parent compound. The cytotoxic activity of these platinum pyrazole complexes toward the murine leukemia cell line was 2.9-3.8 times lower than actvity of cisplatin. The tested compounds varied in their mechanism of action by producing different DNA lesions. The most interesting compound seems to be the complex with chloromethyl groups at N1 of pyrazole rings, which exhibited the highest ability to form bifunctional adducts with DNA in vitro.
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http://dx.doi.org/10.1016/j.jinorgbio.2006.05.001DOI Listing
October 2006
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