Jadwiga Jodynis-Liebert

Poznan University of Medical Sciences, Posen, Greater Poland Voivodeship, Poland

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Publications (38)72.34 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: DMU-212 has been shown to evoke a mitochondrial apoptotic pathway in transformed fibroblasts and breast cancer. However, recently published data indicated the ability of DMU-212 to evoke apoptosis in both mitochondria- and receptor-mediated manner in two ovarian cancer cell lines, namely A-2780 and SKOV-3, which showed varied sensitivity to the compound tested. The pronounced cytotoxic effects of DMU-212 observed in A-2780 cells were related to the execution of extracellular apoptosis pathway and cell cycle arrest in G2/M phase. In view of the great anticancer potential of DMU-212 against A-2780 cell line, the aim of the current study was to assess antiproliferative activity of DMU-212 in xenograft model of ovarian cancer. To evaluate in vitro metabolic properties of cells that were to be injected into SCID mice, uptake and decline of DMU-212 in A-2780 ovarian cancer cell line was investigated. It was found that the concentration of the test compound in A-2780 cells was growing within first eight hours, and then the gradual decline was observed. A-2780 cells stably transfected with pcDNA3.1/Zeo(-)-Luc vector were subcutaneously inoculated into the right flanks of SCID mice. After seven days of the treatment with DMU-212 (50mg/kg b.w), tumor growth appeared to be suppressed in the animals treated with the compound tested. At day 14 of the experiment, tumor burden in mice treated with DMU-212 was significantly lower, as compared to untreated controls. Our findings suggest that DMU-212 might be considered as a potential anticancer agent used in ovarian cancer therapy.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2014; · 2.24 Impact Factor
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    ABSTRACT: It has been reported that methylated analog of resveratrol, 3,4,5,4'-trans-tetramethoxystilbene (DMU-212), demonstrates strong antiproliferative, and proapoptotic activity. The aim of this study was to evaluate the effect of DMU-212 on the activation of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and signal transducer and activator of transcription 3 (STAT3) transcription factors, using a two-stage model of rat hepatocarcinogenesis (HCC) in Wistar rats. Initiation was performed by a single intraperitoneal injection of N-nitrosodiethylamine (NDEA) (200 mg/kg) followed by promotion with phenobarbital (PB) (0.05 %) in drinking water. DMU-212 was administered by gavage in a dose of 20 or 50 mg/kg b.w. two times a week for 16 weeks. There was a significant increase in the activation of all investigated hepatic transcription factors in the NDEA/PB-induced rats. The activation of NF-κB induced by NDEA/PB treatment was suppressed by DMU-212 as evidenced by a reduction of p65 and p50 subunits translocation, DNA binding capacity, increased retention of IκB, and the reduced IKK activity. Moreover, DMU-212 reduced the level of iNOS protein induced by NDEA/PB. Treatment with DMU-212 alone increased the constitutive AP-1 subunits c-Jun and c-Fos levels and c-Jun binding to TRE consensus site. The combined treatment diminished c-Fos level and DNA binding. At a dose of 50 mg/kg, DMU-212 decreased also the STAT3 activation induced by NDEA/PB. These data indicate that DMU-212 may suppress pro-inflammatory transcription factors, particularly NF-κB, and in consequence iNOS expression in rat model of HCC which makes DMU-212 a good candidate for the development of HCC chemopreventive agent.
    Molecular and Cellular Biochemistry 02/2014; · 2.33 Impact Factor
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    ABSTRACT: Polyphenolics can act as prooxidants leading to the generation of reactive oxygen species and electrophilic metabolites which bind to DNA, protein and glutathione. The aim of the present study was to evaluate potential adverse effects of the long-term dietary administration of freeze-dried chokeberry juice to rats. Groups of 8 males and 8 females were exposed via diet to 0; 2; 6; 10 g juice/kg feed for 90 days. Mean food consumption and mean body weight gain of treated animals were comparable with controls. Changes in some hematological parameters were sporadic and non-dose-responsive. Several statistically significant changes in clinical chemistry parameters were considered no toxicologically relevant since they were of small magnitude and lacked correlating findings in histopathology. Histopathological examination did not reveal any changes that could be attributed to chokeberry juice intake. Determination of oxidative damage markers in the liver demonstrated no damage of lipids, proteins and DNA. Chokeberry juice intake improved antioxidant status of rats as evidenced by a decrease in the level of lipid peroxidation, an increase in reduced glutathione concentration and an increase in some antioxidant enzymes activity. It could be concluded that freeze-dried chokeberry juice is safe at doses tested and can be used as a component of food supplements. Keywords: Chokeberry, antioxidant activity, hematology, clinical chemistry.
    Journal of Pharmacy and Nutrition Sciences. 01/2014; 4:154-161.
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    ABSTRACT: Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improve long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain.
    Fitoterapia 09/2013; · 2.23 Impact Factor
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    ABSTRACT: The cytotoxic activity of DMU-212 has been shown to vary in cell lines derived from the same type of cancer, i.e. ovarian, breast and colorectal ones. However, the molecular mechanism of DMU-212 cytotoxicity has not been clarified in colon cancer cells. This study aims to elucidate the mechanism of antitumor effects of DMU-212 in two human colon cancer cell lines, DLD-1 and LOVO. We showed the stronger cytotoxic activity in DLD-1 cells in which DMU-212 evoked a greater pro-apoptotic effect as compared to that of LOVO cells. The analysis of the expression pattern of 84 apoptosis-related genes indicated transcripts specific to the mitochondria-mediated apoptosis pathway in both colon cancer cell lines used. We found that DMU-212 caused up-regulation of pro-apoptotic Bak1, Bok, Bik, Noxa, Bad, Bax, p53 and Apaf1 transcripts level in DLD-1 cell line, whereas anti-apoptotic Bcl-2, Bcl-xL and Bag1 mRNA expression was decreased. Changes in apoptosis-related genes expression were less pronounced in LOVO cells which did not express CYP1B1 protein and showed lower expression of CYP1A1 protein level than that in DLD-1 cells. Our results suggest that anticancer activity of DMU-212 is closely related to its biotransformation catalysed by these cytochrome P450 isoenzymes.
    Toxicology in Vitro 09/2013; · 2.65 Impact Factor
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    ABSTRACT: The aim of the study was to evaluate a protective effect of apple juice on KBrO(3) -induced oxidative stress in rats. Male Wistar rats were administered apple juice per os, 10 ml/kg b.w. for 28 days. On 27 day of the experiment, some rats were given i.p. a single 125 mg/kg b.w. dose of KBrO(3) . Markers of oxidative damage and clinical chemistry parameters were determined. Treatment with apple juice prior to KBrO(3) challenge prevented an increase in hepatic and renal microsomal lipid peroxidation by 25 and 44%, respectively, increased the activity of antioxidant enzymes in the liver by 29 - 59% and decreased the plasma content of carbonyl groups by 19%. Aminotransferases activity in plasma was reduced by 19% and 36%, concentrations of plasma bilirubin, cholesterol and creatinine were suppressed by 21%, 16% and 26%, respectively, in rats supplemented with juice before KBrO(3) injection. No protective effect of apple juice on nuclear DNA was observed. Supplementation with cloudy apple juice to some extent attenuated oxidative damage induced by KBrO(3) in the liver and kidney of rats as evidenced by alterations of certain oxidative stress markers and clinical chemistry parameters. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 10/2012; · 2.07 Impact Factor
  • 47th Congress of the Polish Biochemical Society and Polish-German Biochemical Societies Joint Meeting. Poznań Poland; 09/2012
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    ABSTRACT: In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4'5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC(50)=0.71 μM) and SKOV-3 (IC(50)=11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 and p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212.
    Toxicology and Applied Pharmacology 06/2012; 263(1):53-60. · 3.98 Impact Factor
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    ABSTRACT: Because of the lengthening of human life, there is an increased risk of dementia incidence, including Alzheimer disease, which pathogenesis is associated with changes in the cholinergic system of CNS [1]. The search of nonselective inhibitors of acetyl- and butyrylcholinesterases (AChE, BuChE) may be a key way in optimization of pharmacotherapy of these neurodegenerative disorders [2]. Substances of plant orygin can be a valuable and alternative source of medicinal products used in prevention and treatment of dementias. The main aim of this study was to assess the influence of subchronic (28-fold) administration of ethanol-water extract of Salvia miltiorrhiza root (SE, 200 mg/kg, p.o.) on scopolamine-induced (0.5 mg/kg, s.c.) impairment of short-term and long-term memory of rats coupled with their cholinesterases (AChE and BuChE) activities assessment in hippocampus and frontal cortex. Phytochemical analysis showed the content in the SE of 1,07% tanshinons, 0,15% rosmarinic acid. Moreover, total hydroxycinnamic derivatives expressed as rosmarinic acid and total polyphenols calculated to gallic acid were 6.92% and 12.89%, respectively. It was found that in the passive avoidance test, that SE significantly improved the long-term memory of rats by 174% (p<0,01), whereas after application of scopolamine the similar effect was observed, but it did not reach a statistical significance. Moreover, it was shown that the SE inhibited the AChE activity by 47% (p<0,01) in frontal cortex and by 55% (p<0,01) in the hippocampus of rat brain. In the same group it was also found out that the SE inhibited (not significantly) the activity of BuChE. It seems that due the SE activity it represents a possible option for preventive treatment against risk of some neurodegenerative diseases. Bibliography 1. Davies P, Maloney AJF: Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 1976;2:1403 2. Weinstock, M. Selectivity of cholinesterase inhibition: clinical implications for the treatment of Alzheimer’s disease. CNS Drugs 1999;12:307 Studies founded by the Ministry of Science and Higher Education, project no N 405417836.
    14. Sejmik Zielarski "Zioła - leki, żywność, kosmetyki". Żerków; 05/2012
  • II Conference of Bioactive Plant Compounds - Structural and Applicative Aspects. Puławy, Poland; 09/2011
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    ABSTRACT: Male Wistar rats were treated with chokeberry juice per os, 10 mL/kg/day, for 28 days and a single intraperitoneal (i.p.) dose of N-nitrosodiethylamine (NDEA), 150 mg/kg, or carbon tetrachloride (CCl(4)), 2 ml/kg. The level of hepatic microsomal lipid peroxidation, expressed as thiobarbituric acid reactive substances (TBARS), was increased in animals dosed with NDEA and CCl(4). Juice pretreatment resulted in a significant decrease in TBARS by 53% and 92%, respectively. In rats administered juice alone, 50% decrease in TBARS was noted. The activities of all antioxidant enzymes were decreased in the liver of rats administered either toxicant by 29%-52% as compared to controls. Juice pretreatment resulted in an increase in the activity of catalase, glutathione peroxidase and glutathione reductase by 117%, 56% and 44%, respectively, only in rats challenged with NDEA. Although no response of plasma protein carbonyls to both toxicants was observed, the pretreatment with juice caused a 55% decrease of this parameter in CCl(4)-dosed rats. DNA damage in blood leukocytes induced by either toxicant was slightly reduced, by 24%, in the rats pretreated with juice and administered NDEA. The results of the study showed that pretreatment with chokeberry juice confers some protection against chemical-induced oxidative stress.
    Human & Experimental Toxicology 03/2011; 30(3):199-208. · 1.31 Impact Factor
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    ABSTRACT: Apples abundant in phenolic compounds show a variety of biological activities that may contribute to beneficial effects against some chronic diseases. The aim of our study was to assess the protective effect of cloudy apple juice against chemical-induced oxidative stress in rats. Male Wistar rats were treated with apple juice per os, 10 mL/kg/day for 28 days and with a single dose of N-nitrosodiethylamine (NDEA), 150 mg/kg or carbon tetrachloride (CCl(4)), 2 mL/kg, 24 h before killing. Two groups of rats not pretreated with juice were administered each of the xenobiotics alone. Microsomal lipid peroxidation in the liver was decreased in rats pretreated with juice by 52-87% when compared to animals given NDEA or CCl(4) alone. Pretreatment with juice protected antioxidant enzymes: catalase, glutathione peroxidase and glutathione reductase but not superoxide dismutase. Their activity was recovered by 49-173% when compared to that in rats given either toxicant alone. The plasma activity of paraoxonase 1 was reduced by both toxicants and was increased by 23% in the apple/CCl(4) group. A rise in plasma protein carbonyls caused by the xenobiotics was reduced by 20% only in apple/NDEA-treated rats. Also, in this group of animals, a 9% decrease in DNA damage in blood leukocytes was observed. Phytochemicals in commonly consumed apple juice may protect some macromolecules against oxidative insult induced by xenobiotics.
    European Journal of Nutrition 02/2011; 50(1):53-60. · 3.13 Impact Factor
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    ABSTRACT: The aim of this study was to investigate cytotoxicity, acute and subchronic oral toxicity of an ionic liquid didecyldimethylammonium saccharinate [DDA][Sac] in rat. IC(50) values tested on six human cell lines varied from 1.44 microM to 5.47 microM. The compound tested was classified to the 4th toxicity class with a fixed LD(50) cut-off value 500 mg/kg. Organ pathology induced by [DDA][Sac] in an acute experiment included exfoliation of the surface layer of the colon and alveolar septa in lung parenchyma. In a subchronic experiment rats were administered 10, 30 and 100 mg/kg/day [DDA][Sac] for 28 days. Reduced body weight gain and slightly reduced food consumption was observed particularly in high-dose rats. Slight hematology changes were found only in mid-dose females. Statistically significant changes in clinical chemistry parameters included: increases in the ALT, SDH, ALP and GGT activities, and in glucose, blood urea nitrogen and creatinine concentrations. However, these changes did not occur in both sexes and were not dose-related with the exception of ALP in females. No treatment-related microscopic changes were observed in a subchronic experiment. Under the condition of this study the lowest-observed-adverse-effect level of [DDA][Sac] was considered to be 10 mg/kg/day.
    Regulatory Toxicology and Pharmacology 03/2010; 57(2-3):266-73. · 2.13 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the potential protective effect of beetroot juice in a model of oxidative stress induced by N-nitrosodiethylamine (NDEA) and carbon tetrachloride (CCl(4)). Male Wistar rats were treated with beetroot juice per os, 8 mL/kg/day for 28 days, and a single i.p. dose of the xenobiotics: 150 mg/kg NDEA or 2 mL/kg CCl(4). Simultaneously, two groups of rats not pretreated with juice were given only each of the xenobiotics. The level of microsomal lipid peroxidation in the liver, expressed as TBARS concentration, was increased several fold in rats administered only NDEA or CCl(4). TBARS were decreased by 38% only in rats pretreated with beetroot juice before the administration of CCl(4). In animals pretreated with juice and receiving NDEA, a further increase in TBARS occurred. All of the investigated antioxidant enzymes were inhibited by the administration of either toxicant alone by 26%-77% as compared to controls. Pretreatment with juice caused a partial recovery in the activity of glutathione peroxidase and glutathione reductase, by 35% and 66%, respectively. Superoxide dismutase activity was increased about 3-fold in animals pretreated with juice. Both xenobiotics caused a rise in plasma protein carbonyls, which were reduced by 30% in rats pretreated with juice and then injected with NDEA. Similarly, DNA damage in blood leukocytes caused by either toxicant was slightly diminished, by 20%, in the rats treated with juice before NDEA administration. It could be concluded that pretreatment with beetroot juice can counteract, to some extent, xenobiotic-induced oxidative stress in rats.
    Journal of Agricultural and Food Chemistry 04/2009; 57(6):2570-5. · 3.11 Impact Factor
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    ABSTRACT: The ethyl ether extract from Aquilegia vulgaris (L.) (Ranunculaceae) contains a lot of phenolic acids. Their hydroxyl groups are capable of donating hydrogen atoms at the initial stage of lipid peroxidation (LPO), which inactivates hydroxyperoxides formed from polyunsaturated fatty acids (PUFAs) and leads to breakdown of the propagation chain. Rats pretreated with acetaminophen (APAP) (600 mg/kg b.w., p.o.) were given ethyl ether extract (100 mg/kg b.w., p.o.) obtained from A. vulgaris herb. The study parameters measured were microsomal lipid peroxidation, reduced glutathione, and the activity of hepatic antioxidant enzymes and some drug metabolizing enzymes. The treatment with ethyl ether extract of the herb produced a 87-95% decrease in uninduced and Fe2+/ascorbate-stimulated microsomal lipid peroxidation in the liver of rats receiving APAP. Hepatic glutathione level depleted by APAP increased significantly (by 18%) after the extract treatment. Antioxidant enzyme activity in the liver, inhibited by APAP, was found to increase after administration of the extract: catalase by about 36%, glutathione reductase by 27% and glutathione S-transferase by 29%. Glucose-6-phosphate dehydrogenase, which decreased after APAP administration, increased again by 26% after extract treatment. The extract tested did not affect the activity of DT-diaphorase. The cytochrome P450 content, depleted by APAP, increased as much as by 100% after the treatment. The activities of NADPH-cytochrome P450 reductase, aniline hydroxylase and aminopyrine N-demethylase were not affected. The protective effect of the Aquilegia vulgaris extract in APAP-induced liver injury was mediated by its antioxidant activity. The extract did not inhibit the formation of reactive intermediate metabolites of APAP.
    International Journal of Occupational Medicine and Environmental Health 02/2009; 22(2):115-23. · 1.31 Impact Factor
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    ABSTRACT: The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD(50) cut-off value of 500 mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100 mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10 mg/kg/day.
    Drug and Chemical Toxicology 01/2009; 32(4):395-404. · 1.29 Impact Factor
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    ABSTRACT: Six groups of male Wistar rats were treated as follows: in groups II, III and V liver damage was induced by CCl4 (per os, 1590 mg/kg b.w. day) given 2 days a week for 6 weeks; group III was treated simultaneously with ethanol extract of Aquilegia vulgaris (100 mg/kg b.w. day) for 6 weeks; group V with silymarin, positive control, at a dose of 100mg/kg b.w. day for 6 weeks; and groups IV and VI received only the extract or silymarin, respectively. Microsomal lipid peroxidation in the liver increased following CCl4 treatment by 61–213% and was not changed significantly by the extract. The effect of silymarin was more pronounced, 19–52% decrease in the lipid peroxidation level. Hepatic glutathione was depleted by 22% in CCl4-treated rats. The extract tested did not change this parameter. The activity of antioxidant enzymes was significantly reduced after CCl4 administration, by 42–63%. Co-administration of the extract or silymarin resulted in significant increase in these enzymes activity; however, the basal level was not reached. Hepatic hydroxyproline concentration was elevated over 5-fold in comparison with controls. Co-administration of the extract or silymarin decreased the level of hydroxyproline by 66% and 55%, respectively. Activity of serum hepatic enzymes was elevated in rats treated with CCl4 by 47–8700%. Both the extract and silymarin reduced significantly these enzymes’ activity. The extract caused a fall in bilirubin and cholesterol level in rats treated with CCl4 by 42% and 17%, respectively. Histopathological examination revealed less-severe fibrosis in rats co-administered the extract or silymarin when compared to animals treated with CCl4 alone.
    Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 01/2009; · 1.43 Impact Factor
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    ABSTRACT: The dual nature of ionic liquids has been exploited to synthesize materials that contain two independent biological functions by combining anti-bacterial quaternary ammonium compounds with artificial sweetener anions. The synthesis and physical properties of eight new ionic liquids, didecyldimethylammonium saccharinate ([DDA][Sac]), didecyldimethylammonium acesulfamate ([DDA][Ace]), benzalkonium saccharinate ([BA][Sac]), benzalkonium acesulfamate ([BA][Ace]), hexadecylpyridinium saccharinate ([HEX][Sac]), hexadecylpyridinium acesulfamate ([HEX][Ace]), 3-hydroxy-1-octyloxymethylpyridinium saccharinate ([1-(OctOMe)-3-OH-Py][Sac]), and 3-hydroxy-1-octyloxymethylpyridinium acesulfamate ([1-(OctOMe)-3-OH-Py][Ace]), are reported, as well as the single crystal structures for [HEX][Ace] and [1-(OctOMe)-3-OH-Py][Sac]. Determination of anti-microbial activities is described for six of the ILs. While some exhibited decreased anti-microbial activity others showed a dramatic increase. For two of the ionic liquids, [DDA][Sac] and [DDA][ACE], oral toxicity, skin irritation, and deterrent activity was also established. Unfortunately, both ILs received a Category 4 (harmful) rating for oral toxicity and skin irritation. However, deterrent activity experiments point to use as an insect deterrent, as both ILs scored either ''very good'' or ''good'' against several types of insects.
    New Journal of Chemistry 01/2009; · 2.97 Impact Factor
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    ABSTRACT: The phytochemical resveratrol, which is found in grapes and red wine, has been reported to have a variety of biological properties. It was shown in our previous research that introduction of additional hydroxyl groups into the stilbene structure increases the biological activity of resveratrol. In this study, the activity of 3,3',4,4',5,5'-hexahydroxystilbene (M8) was investigated in ZR-75-1, MDA-MB-231 and T47D human breast cancer cells. For evaluation of cytotoxic activity of M8, clonogenic and cell proliferation assays were used. The IC50 values obtained in the clonogenic assay were 0.846 microM for T47D, 8.53 microM for ZR-75-1 cells and 25.5 microM for MDA-MB-231, while IC50 values obtained in the cell proliferation assay were significantly higher: 90.1 microM, 98.4 microM, 127.8 microM for T47D, ZR-75-1 and MDA-MB-231 cells, respectively. Compound M8 caused the activation of caspase-8 in MDA-MB-231 cells (marker of extrinsic apoptotic pathway), while activities of caspase-9 (marker of intrinsic apoptotic pathway) and caspase-3 were increased in all 3 tested cell lines. Activation of caspase-9 and caspase-3 was connected with loss of mitochondrial potential and increase of p53, which could have an impact on downregulation of mitochondrial superoxide dismutase (MnSOD) seen in our experiments. MnSOD is a key enzyme providing antioxidative defense in mitochondria - the cellular center of reactive oxygen species' generation. Downregulation of MnSOD can therefore cause a significant decrease of antioxidant defense in cancer cells. An increase of oxidative stress conditions was suggested by loss of reduced glutathione in tested cells. Since cancer cells are usually under permanent oxidative stress, additional increased ROS generation as a result of the interaction of M8 with the mitochondrial respiratory chain and a decrease in oxidative defense can therefore be a promising method for selective elimination of cancer cells.
    Toxicology in Vitro 09/2008; 22(5):1361-70. · 2.65 Impact Factor
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    ABSTRACT: Resveratrol, a natural phytoalexin found mainly in grapes, possesses a variety of beneficial activities including anticancer, antimicrobial and antiviral. However, there is no information about its effects on kinetoplastid parasites such as Leishmania. Leishmania is a human pathogen responsible for a spectrum of diseases known as leishmaniases and a significant health problem in many parts of the world. In this study, we investigated effects of resveratrol and its hydroxylated analogues on Leishmania major, a causative agent of zoonotic cutaneous leishmaniasis in the Old World. Resveratrol showed antileishmanial activity against promastigotes in vitro and, more importantly, was effective against intracellular amastigotes, a parasite life stage infectious in humans, as detected in in vitro macrophage assay. The hydroxylated stilbenes tested in this study also showed antileishmanial activity against promastigotes, the most promising being 3,4,4',5'-tetrahydroxy-trans-stilbene. This compound showed excellent antileishmanial activity against extracellular promastigotes in vitro but not intracellular amastigotes. Our results suggest that resveratrol may be useful as a therapeutic agent to treat leishmaniasis and warrant its further assessment in animal models of disease.
    Parasitology Research 01/2008; 102(1):91-7. · 2.85 Impact Factor

Publication Stats

213 Citations
72.34 Total Impact Points

Institutions

  • 1999–2014
    • Poznan University of Medical Sciences
      • • Department of Toxicology
      • • Department of Pharmacology
      Posen, Greater Poland Voivodeship, Poland
  • 2010
    • Uniwersytet Medyczny im.Karola Marcinkowskiego w Poznaniu
      • Department of Toxicology
      Poznań, Greater Poland Voivodeship, Poland
  • 2008
    • The Walter and Eliza Hall Institute of Medical Research
      • Division of Infection and Immunity
      Melbourne, Victoria, Australia
  • 2005
    • Medical University of Lublin
      • Department of Clinical Pathomorphology
      Lublin, Lublin Voivodeship, Poland