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Anna Merwid-Ląd, Małgorzata Trocha,
Ewa Chlebda-Sieragowska,
Tomasz Sozański,
Jan Magdalan,
Dorota Ksiądzyna,
Andrzej Szuba,
Maria Kopacz,
Anna Kuźniar,
Dorota Nowak,
Małgorzata Pieśniewska,
Lidia Fereniec-Gołębiewska,
Adam Szeląg
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ABSTRACT: Background: The aim of the study was to evaluate the effect of cyclophosphamide (CPX) and morin-5'-sulfonic acid sodium salt (NaMSA) on plasma asymmetric dimethylarginine (ADMA) level and dimethylarginine dimethylaminohydrolase (DDAH) activity in rat liver. Methods: The study was performed on Wistar rats receiving normal saline, CPX (15 mg/kg/day), NaMSA (100 mg/kg/day) or both CPX and NaMSA for 10 consecutive days. Results: Significant decrease in ADMA level was found in all groups when compared to the control. DDAH activity in the liver was significantly higher in CX group compared to the control group. Conclusion: Obtained results of ADMA/DDAH pathway parameters require further research.
Pharmacological reports: PR 01/2013; 65(1):201-7. · 2.44 Impact Factor
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Małgorzata Trocha,
Anna Merwid-Ląd,
Tomasz Sozański,
Ewa Ewa Chlebda-Sieragowska,
Andrzej Szuba,
Piotr Dzięgiel,
Małgorzata Pieśniewska,
Lidia Fereniec-Gołębiewska,
Joanna Kwiatkowska,
Agnieszka Gomułkiewicz,
Lucja Cwynar-Zając,
Renata Brykner,
Adam Szeląg
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ABSTRACT: Background: We evaluated effect of ezetimibe on selected parameters determining NO level in rat liver subjected to ischemia reperfusion (IR). Methods: Rats received ezetimibe (5 mg/kg) (groups E0 and EIR) or saline solution (groups C0 and CIR) intragastrically for 21 days. Then, the livers of CIR and EIR underwent ischemia (60 min) and reperfusion (4 h). Blood samples were obtained before surgery to estimate activities of aminotransferases, and just before ischemia and during reperfusion to estimate asymmetric and symmetric dimethylarginine (ADMA, SDMA) and arginine (Arg) levels. After IR, dimethylarginine dimethylaminohydrolase (DDAH) activity and endothelial nitric oxide synthase (eNOS) protein concentration were measured in liver homogenates. DDAH and protein arginine methyltransferase (PRMT) mRNA were quantified by real-time PCR in liver tissue samples. Results: In CIR, the ADMA level was significantly higher compared to all other groups in 30 min and to E0 group in 120 min of reperfusion. In EIR, ADMA was low, compared to non-ischemic groups. At 30 and 120 min of reperfusion, in non-ischemic groups the level of Arg and Arg/ADMA ratio were significantly higher than in ischemic groups and E0 was the group with the highest levels of those parameters of all. In CIR, eNOS protein concentration was significantly lower than in ezetimibe-treated groups. Activity of DDAH was significantly higher in E0 than in non-treated groups. In ischemic groups, DDAH mRNA expression was significantly higher than in non-ischemic ones and PRMT mRNA expression was significantly higher in C0 than in all other groups. Conclusions: Influence of ezetimibe on ADMA/DDAH/NO pathway demonstrated in this work may suggest protective properties of this drug on rat livers injured by IR and, to a lower extent, on livers non-subjected to IR.
Pharmacological reports: PR 01/2013; 65(1):122-33. · 2.44 Impact Factor
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ABSTRACT: Previous studies proved that food strongly enhanced the bioavailability of vinpocetine. Food may change the pharmacokinetics of a drug by affecting various factors, including gastrointestinal pH. However, the influence of proton pump inhibitor-induced pH alterations on vinpocetine pharmacokinetics is not known. The aim was to evaluate the influence of omeprazole on the pharmacokinetics of oral vinpocetine. One group of male Wistar rats received single oral doses of vinpocetine (2 mg/kg - regimen V). In the second group, omeprazole (10 mg/kg) was administered intraperitoneally for 5 days before vinpocetine administration (regimen OV). For analysis of vinpocetine pharmacokinetics, blood samples were obtained before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 h after vinpocetine administration. Vinpocetine concentrations were measured by high performance liquid chromatography (HPLC). The mean values of AUC(0-t), AUC(0-inf) and C(max) in regimen V were very similar to respective values in regimen OV. The mean T(max) in both regimens was estimated for 1.5 h. There were no statistically significant differences between both regimens. In conclusion, omeprazole did not affect the pharmacokinetic profile of vinpocetine.
Pharmacological reports: PR 09/2011; 63(5):1258-63. · 2.44 Impact Factor
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01/2011; 20(6):683-690.
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ABSTRACT: Vipera berus is the only naturally occurring venomous snake in Poland. Its venom is primarily vasculotoxic and evokes both local and systemic findings. The aim of the study was to review a series of clinical cases of V berus bites occurring in southwest Poland.
The charts of 26 patients (age range, 16-66 years; mean, 42 years) hospitalized with V berus bites were retrospectively analyzed using a data collection tool. Demographic and clinical data were extracted.
The most common local findings of envenomation were edema of the bitten limb with associated extravasations observed in 24 (92.3%) patients, but in only 1 (3.8%) case did the edema spread to the trunk. In 22 (84.6%) cases edema disappeared within 2 weeks after the bite. Systemic disturbances observed in the patients were: shock (1 case), mild transient hypotension (1 case), prolonged hypotension (3 cases), bronchospasm and laryngeal edema (1 case), diarrhea (1 case), transient supraventricular arrhythmias (2 cases), neutrophilic hyperleukocytosis (2 cases), and thrombocytopenia below 50000 cells/microL (5 cases). In 16 patients (61.5%) the envenomation was classified as moderate and this type was predominant. Six cases were classified as severe. No fatal case was reported. Treatment included the administration of specific antivenom in 14 cases (in all severe and half of moderate cases) and symptomatic treatment applied in all cases.
Moderate envenomation prevailed among the patients analyzed in the study. Antivenom treatment is primarily necessary in cases of severe (grade 3) and in some cases of moderate (grade 2) envenomation, especially in patients with persistent or recurring hypotension.
Wilderness and Environmental Medicine 06/2010; 21(2):114-9. · 0.94 Impact Factor
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01/2010; 19(1):43-50.
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ABSTRACT: Water-soluble quercetin-5'-sulfonic acid sodium salt (NaQSA) and morin-5'-sulfonic acid sodium salt (NaMSA) could exert an antagonistic effect on cadmium intoxication. The aim of the study was to examine the influence of these substances on superoxide dismutase (SOD) and glutathione (GSH) levels in the mouse liver in the subacute cadmium intoxication model. NaQSA and NaMSA significantly counteracted cadmium-induced decreases in SOD and GSH levels. No significant differences in SOD and GSH levels between groups exposed to cadmium receiving NaQSA or/and NaMSA were observed.
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 04/2009; 62(2):105-8. · 1.43 Impact Factor
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ABSTRACT: Liver function appears to be well maintained in old age. However, the current state of knowledge about liver aging processes is incomplete. In this study, using extracorporeal liver perfusion model, we evaluated the differences between liver function in young and old rats.
Livers were harvested from groups of young (2 months) and old (12 months) rats and perfused for 2 hours with a perfusion fluid. After 10, 30, 60, 90 and 120 minutes of perfusion, glucose concentration as well as enzyme levels (alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase) were measured. On completion of perfusion all bile produced was collected.
All measured parameters changed significantly as a function of perfusion time in both groups. Changes in enzyme levels were most evident between 90 and 120 minutes of perfusion. In contrast to old rats, where glucose concentration decreased during all time periods of perfusion, in young rats the glucose concentration increased at the beginning of perfusion.
The results suggest that livers obtained from older rats are damaged to a greater extent and are more susceptible to unfavorable conditions during perfusion than livers obtained from younger rats. Also, single measurement of liver enzymes is not enough for complete liver function assessment.
Hepato-gastroenterology 07/2007; 54(76):1207-11. · 0.66 Impact Factor
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Pharmacological reports: PR 01/2007; 59(suppl. 1):210-216. · 2.44 Impact Factor
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Pharmacological reports: PR 01/2007; 59(suppl. 1):269-274. · 2.44 Impact Factor
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ABSTRACT: Glaucoma is the main cause of blindness in the developed countries. Its progress can be diminished by decreasing intraocular pressure (IOP) using pharmacological or surgical treatment. Antiglaucoma agents, alpha 2-adrenergic's receptor agonists have been known for several years as IOP lowering. Due to the fact that the majority of them turned out to be imidazoline receptor agonists, it is worth checking if selective imidazoline receptor (l1) agonists alter IOP. Preliminary animal experiments show that they lower IOP. In our study we examined the influence of rilmenidine, a potent l1 receptor agonist, on IOP in rabbits. Furthermore, we tried to find out whether l1 and alpha 2 receptor antagonists (efaroxan and rauwolscine) counteract the pharmacological effect of rilmenidine.
The study was conducted on adult male White New Zealand rabbits. All the substances were administered topically, and IOP was measured by applanation tonometry after topical anaesthesia before and 1, 3 and 5 hours after drug instillation.
Rilmenidine showed the lowering effect on IOP at the concentration of 0.4%. Efaroxan and rauwolscine partly inhibited rilmenidine effect.
Rilmenidine is a potential antiglaucoma agent, though further studies are necessary.
Klinika oczna 02/2004; 106(1-2):7-10.
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ABSTRACT: Calcium plays a crucial role in physiological process in liver cells however in high concentrations these ions can be pathogenic and lead to cell death. Mechanisms responsible for maintaining calcium ion concentration gradient in physiological conditions include transmembrane transport, storage in intracellular organelles and binding to cytoplasmatic proteins. Ischemia, sepsis, anoxia and action of toxins are responsible for uncontrolled influx of calcium and consequently cell damage. Liver damage during its preservation for transplantation is connected with dysfunction of many enzymes, damage of cell membrane and cytoskeleton proteins. During reperfusion Kupffer cells are activated, reactive oxygen species are produced and microcirculation is disordered by calcium--dependent processes. Calcium channel blocking (CCB) drugs exhibit immunomodulatory impact and positive interaction with cyclosporine or tacrolismus. They also have cytoprotective properties during preservation end reperfusion time. They seem to improve liver function, decrease liver cell damage, elevate bile production, decrease lipid peroxydation and free radicals production. But in some experiments CCB do not modify calcium concentration. More research on preservation conditions is needed to increase the probability of a successful liver transplantation.
Annals of transplantation: quarterly of the Polish Transplantation Society 02/2004; 9(3):5-11. · 2.02 Impact Factor
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ABSTRACT: Histamine isolated from many different tissues, acts via three types of histamine receptors: H1, H2 and H3. In peripheral tissues histamine is mainly stored in mast cells (MC). Presence of mast cells was proved also in mammals' uteri. In human uterus the majority of mast cells are located close to smooth muscle cells. It might indicate that MC plays a role in tissue remodelling during the menstrual cycle. The quantity and activity of mast cells is in connection with hormonal status of the organism. Although there are some differences, human uterine mast cells are similar to the mast cells isolated from other tissues. It is suggested that histamine is important for normal ovulation, blastocyst implantation, placental blood flow regulation, lactation and contractile activity of uterus. Histamine may also play a role in pathological processes such as pre-eclampsia or preterm delivery. The participation of mast cells and histamine in blastocyst implantation is very controversial. In W/Wv mice (without mast cells) normal implantation was observed. It denies the main role of mast cells in this process but dos not exclude histamine action. In mice the major source of histamine are uterine epithelial cells during early pregnancy. The influence of cytokines on blastocyst implantation and the role of histamine in cytokines release from the uterine mast cells are also very unclear.
Ginekologia polska 08/2002; 73(7):627-35. · 0.41 Impact Factor
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ABSTRACT: The presence of the mast cells was confirmed not only in the uterus but also in the placental tissue. Mediators released from the placental mast cells may play a role in regulation of placental blood flow and normal blood pressure. Processes such uptake and clearance of vasoactive mediators may be upset in those women who developed pre-eclampsia. Histamine released from the placental mast cells may be involved in the mechanisms controlling myometrium contractility during the labour at term and preterm delivery. There is a correlation between the level of placental histamine and presence (or not) uterus contractility. Histamine produce a contractile response in isolated myometrial strips, in the majority of mammals, via H1 histamine receptors activation, but in some species e.g. rat, predominant response of uterus is relaxation (via H2 histamine receptors activation). Predominant response of the human uterus to histamine is contraction. Relaxation of human myometrial strips may be evoked after earlier usage of H1 receptors antagonists, although some H2 receptors agonists (e.g. dimaprit) induce the relaxation of human uterus without H1 receptors antagonists. Myometrium contractile activity is under control of sexual hormones. Neither the presence of H3 histamine receptors on the human myometrial smooth cells nor its role in the female reproductive system regulation was proved. Lack of the functional H3 receptors either on the smooth muscle cells or neuronal components of the animals' myometrium was shown in some studies.
Ginekologia polska 08/2002; 73(7):636-44. · 0.41 Impact Factor
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ABSTRACT: An increase in calcium ion concentration in the cytoplasm due to the influence of various toxic agents causes disturbances in the structure and function of hepatocytes, leading to their damage and even death. Calcium ions enter the cell mostly through calcium channels, therefore, it has been suggested that calcium channel inhibitors (CCI) could protect hepatocytes from the action of toxic substances. The present study investigated the effect of the selected CCI (nifedipine, nitrendipine and verapamil) on liver function, measured by the efficiency of oxidation reaction, in this case by determination of the rate of antipyrine metabolism. The experiment was carried out using the method of extracorporeal liver perfusion (ELP). None of the studied CCI applied at a concentration of 50 micromol/l increased the rate of antipyrine metabolism over the whole period of ELP. However, supplementation of perfusion fluid with nifedipine, nitrendipine or verapamil at a concentration of 20 micromol/l considerably improved metabolic liver efficiency during the second hour of perfusion, i.e. at the time, when large number of hepatocytes started to perish, which could indicate protective action of the tested CCI. However, the CCI-induced acceleration of antipyrine metabolism was not a result of their influence on calcium channels, since these drugs block calcium channels, when given at the concentrations as high as 100-400 micromol/l. Moreover, it seems that facilitation of antipyrine metabolism during ELP was not due to their action on microsomal enzymes because CCI were administered at very low concentrations, besides, they are metabolic inhibitors, and not inducers. The present experiment suggests that low concentrations of CCI can exert hepatoprotective effect. However, confirmation of this conclusion requires further studies using other experimental methods.
Polish journal of pharmacology 55(2):203-8.
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ABSTRACT: Quercetin-5'-sulfonic acid sodium salt (NaQSA) exerts good aqueous solubility, strong antioxidant activity and low toxicity.
The aims of this study were to investigate the effect of NaQSA on superoxide dismutase (SOD) activity and ADMA/DDAH pathway during extracorporeal liver perfusion (ELP).
The study was carried out on male Wistar rats. Isolated livers were perfused with Krebs-Henseleit bicarbonate buffer (KHB) + 1 microM ADMA (group C), or with KHB + 1 microM ADMA and either 10 microM NaQSA (Q10) or 50 microM NaQSA (Q50). In group 0 (sham) livers were perfused with KHB alone. Levels of ADMA, alanine (ALT) and aspartate (AST) aminotransferases activities were measured during perfusion. After 90 min. of perfusion superoxide dismutase (SOD) and dimethylarginine dimethylaminohydrolase (DDAH) activities were estimated in liver homogenates.
DDAH activity in Q10 group was significantly higher as compared to control and Q50 groups. No significant differences were observed between Q50 and control group. The decrease in ADMA concentration during perfusion was observed in all groups, but the most pronounced in the group Q10 and the least in group Q50. During perfusion AST activities were the lowest in Q50 group. No significant difference in SOD activity in groups perfused with NaQSA as compared to control group was noted.
The impact of NaQSA on ADMA/DDAH system depends on its concentration. In lower concentration NaQSA exerted some beneficial properties which vanished in higher concentration. No increase in SOD activity during perfusion with NaQSA was observed.
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 21(4):423-31.
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ABSTRACT: We evaluated the effect of simvastatin (SV) on the oxido-redox state in rat livers submitted to ischemia-reperfusion (I/R). Rats received SV (groups: S, S-IR) or saline solution (groups: C, C-IR) intragastrically (25 mg/kg) for 21 days. Before homogenization, rat livers (C-IR, S-IR) underwent ischemia (40 min) and reperfusion (60 min). Activities of such antioxidative enzymes as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as lipid peroxides (LPO) level as indicator of oxidative stress were then estimated in the homogenates. All these parameters were measured spectrophotometrically. Additionally, alanine and asparagine aminotransferase (ALT, AST) levels were estimated in the blood before and after I/R. In groups C and S all examined parameters were similar regardless of SV-treatment. I/R produced significant increases in GPx and CAT activities only in the C-IR group. Conversely, GPx activity was significantly decreased and ALT and AST increased significantly in the S-IR group. SV did not evoke any noticeable protective changes in rat livers after 3 weeks of treatment. After I/R, some of the observed properties could suggest that SV may have even made liver function and the oxidative state worse.
Pharmacological reports: PR 62(4):757-62. · 2.44 Impact Factor
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ABSTRACT: Hydroxymethylglutaryl-CoA reductase inhibitors play a role in nitric oxide synthesis. In this study, the impact of simvastatin (SV) on the levels of nitric oxide synthases, and arginine (Arg) and its derivatives was evaluated in rat liver under ischemia-reperfusion (I/R) conditions. Rats received SV (25 mg/kg) (groups S and S-IR) or saline solution (groups C and C-IR) intragastrically for 21 days. The livers of groups C and S were homogenized after treatment while those of groups C-IR and S-IR underwent ischemia and reperfusion before homogenization. Endothelial (eNOS) and inducible (iNOS) nitric oxide synthase concentrations were determined in the homogenates. Alanine and asparagine aminotransferase (ALT, AST, respectively), arginine (Arg), and asymmetric (ADMA) and symmetric (SDMA) methylarginine levels were determined in the blood before I/R and during reperfusion. I/R injury produced significant increases in aminotransferase, ADMA, eNOS, and iNOS, but decreases in Arg and Arg/ADMA levels. Arg concentration increased significantly after warm ischemia in the S-IR group, but decreased significantly during the first 30 minutes of reperfusion in both the S-IR and C-IR groups. eNOS concentration was significantly higher in group S than in group C. Both I/R and SV exerted no influence on SDMA concentration. SV exerted a protective action by increasing eNOS levels under normal conditions and Arg levels after ischemia and by preventing a significant increase in iNOS concentration after I/R. SV had no effect on ADMA concentration under normal and pathological conditions.
Pharmacological reports: PR 62(2):343-51. · 2.44 Impact Factor
