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Biomedical subjects

B Wachowicz

Publications and source records attributed to B Wachowicz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Adhesion of blood platelets to collagen and fibrinogen after treatment with cisplatin and its complex with glutathione.

Cisplatin (cis-diamminedichloroplatinum II, CDDP) is one of the most widely used chemotherapy drugs. Unfortunately, it induces serious side effects such as haematological toxicity. The aim of the present study was to evaluate the effect of CDDP on the first step in blood platelet activation-platelet adhesion, induced by thrombin or adenosine diphosphate (ADP), to collagen and fibrinogen. The action of cisplatin was compared with the action of cisplatin glutathione complex (GS-Pt) on platelet adhesion and on free radical generation measured by chemiluminescence. Pretreatment of blood platelets with cisplatin (0.1-20 microM) caused a dose- and time-dependent reduction of platelet adhesion to collagen and fibrinogen (p <0.05). The GS-Pt complex (20 microM, 30 min) had a stronger inhibitory effect on this process. Moreover, the complex (R2 = 0.992; p <0.05) also stimulated the chemiluminescence of blood platelets to a greater extent than CDDP alone (R2 = 0.999; p <0.01). The results suggest that inhibition of platelet adhesion in the presence of cisplatin and its complex with glutathione correlates with the generation of reactive oxygen species in these cells.

Animals↗
PubMed2000

Endotoxins stimulate generation of superoxide radicals and lipid peroxidation in blood platelets.

Lipopolysaccharide (LPS, endotoxin) is an important structural constituent of the membrane of gram-negative bacteria with a wide range of biological effects. It can activate blood platelets. The purpose of present study was to determine the direct effect of endotoxins from Proteus mirabilis, differing significantly in their composition, on the generation of superoxide radicals and thiobarbituric acid reactive substances (TBARS) in blood platelets. Superoxide radicals were measured by means of superoxide dismutase-inhibitable reduction of cytochrome C. The TBARS determination (malonyldialdehyde) was used as a marker of endogenous arachidonate metabolism and thromboxane A2 synthesis. Results demonstrate that three endotoxins (LPS S1959, LPS R110, LPS R45) after 2 min of action, even at the lowest concentration (0.03 microg/10(8) platelets) stimulated the generation of TBARS and release of superoxide radicals. All LPS contain lipid A as a component but differ in their chemical composition in the polysaccharide part. It is suggested that the observed effects of LPS on blood platelets are attributable to their lipid A portion.

Animals↗
PubMed1999

Changes in blood platelets exposed to UV-B radiation.

The effects of UV-B radiation (312 nm) on the pig-blood platelet secretory process (platelet activation) and platelet lipid peroxidation have been studied. The responses of platelets to UV-B radiation are compared with the response of these cells to thrombin, which is a strong platelet agonist. The obtained results show that exposure of blood platelets to UV-B radiation (1.2 mW/cm2, 0.072-8.64 J/cm2) causes dose-dependent platelet lipid peroxidation (measured as thiobarbituric acid reactive substances, TBARS) and release of adenine nucleotides and proteins from irradiated platelets. The dose-dependent release of platelet compounds from irradiated platelet does not correlate with the activity of platelet lactic dehydrogenase (marker of cell lysis) in the extracellular medium. It seems that UV-B radiation can partly activate platelets by stimulating the platelet secretory process and metabolism of arachidonate.

Animals↗
PubMed1999

Response of blood platelets to resveratrol.

The phytochemical resveratrol (3,4',5-trihydroxystilbene), which is found in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet and anti-carcinogenic effects. The aim of the present study was to evaluate the effects of trans-resveratrol on adhesion of blood platelets to collagen, as well as on thrombininduced platelet aggregation and malonyldialdehyde (MDA) production in vitro. Pretreatment of platelets with resveratrol (50 microg/ml) inhibited their adhesion to collagen (by 32% in resting platelets and by 57% in thrombin-activated platelets after 1 h of preincubation) and thrombin-induced platelet aggregation (by 59% after 30 min preincubation). Resveratrol also had an inhibitory effect on the generation of malonyldialdehyde (a marker of thromboxane A(2) synthesis) measured as thiobarbituric reactive substance in thrombin-activated platelets.

Journal Article↗
PubMed1999

Selenium compounds inhibit the biological activity of blood platelets.

The action of inorganic forms of selenium (Se) on blood platelet aggregation, secretion and the arachidonate pathway in vitro was studied. It was shown that sodium selenite, after 30 min preincubation, inhibited platelet aggregation induced by 0.1 U/ml of thrombin and by 10 microM ADP (about 30% inhibition of aggregation after pretreatment of platelets with 10(-4) M of Se). Contrary to sodium selenite, sodium selenate did not affect the platelet aggregation induced by either agonist. Pretreatment of blood platelets with sodium selenite resulted in a statistically significant decrease in adenine nucleotide secretion ( P < 0.01) and release of malonyldialdehyde (MDA), produced in equal amounts to TXA(2) , in thrombin-stimulated platelets ( P <0.001). However, selenite did not change the level of MDA/TXA(2) in sodium arachidonate-stimulated platelets. We conclude that the inhibitory effects of sodium selenite on platelet activation could be the result of decreased synthesis and release of secondary agonists (TXA(2), ADP) in stimulated platelets. It is also possible that sodium selenite blocks the release of arachidonic acid from platelet membranes via phospholipases.

Journal Article↗
PubMed1999

The effect of cis-diamminedichloroplatinum, selenite and a conjugate of cisplatin with selenite [(NH3)2Pt(SeO3)] on oxidative stress in blood platelets measured by chemiluminescence method.

The effects of cisplatin, sodium selenite and a conjugate of these compounds [(NH3)2Pt(SeO3)] on the generation of free radicals in blood platelets measured by chemiluminescence method were investigated in vitro. In platelets incubated with cisplatin (20 microM, 5 min) a dose-dependent increase of chemiluminescence was observed (p < 0.05). Contrary to the stimulatory action of cisplatin (20 microM) on the production of free radicals, selenite (1 microM) and its conjugate with cisplatin (20 microM) had only slight effects on the oxidative stress in platelets (p < 0.05). The observed increase of chemiluminescence after cisplatin action correlated with a decrease of platelet free thiols present in reduced glutathione. Pre-treatment of blood platelets with buthionine sulfoximine (50 microM, 1 h, 37 degrees C) leading to a decrease of glutathione reduced the cisplatin-induced generation of free radicals in these cells (p < 0.05).

Animals↗
PubMed1999

Stimulatory effects of endotoxin on the platelet secretory process.

The effects of the lipopolysaccharides (LPS) of Proteus mirabilis (smooth and rough types), differing significantly in their composition on the release of compounds stored in specific platelet granules, were studied. There are two main types of secretory granules in blood platelets. Dense granules contain adenine nucleotides, and in alpha-granules different proteins are stored. The LPS were found to cause a dose-dependent release of proteins and adenine nucleotides. In the extracellular medium LDH activity was not present. The results presented in this study indicate that LPS from P. mirabilis act directly on blood platelets and induce the platelet secretory process. In comparison with thrombin, a strong platelet agonist, the action of the endotoxins tested was weak.

Adenine Nucleotides↗
PubMed1999

Inhibitory effect of resveratrol on free radical generation in blood platelets.

Resveratrol (3,4',5-trihydroxystilbene), a compound found in many plants, has been shown to prevent coronary heart diseases and to exert a variety of antiinflammatory and anticancerogenic effects. It is effective in lowering the level of serum lipids and in inhibiting platelet aggregation. We evaluated the effect of trans-resveratrol on the production of free radicals in pig blood platelets and showed that resveratrol inhibited the production of different reactive oxygen species (O2*-, H2O2, singlet oxygen and organic radicals) measured by the luminol-dependent chemiluminescence in resting platelets (P < 0.05). Resveratrol inhibited also the generation of radicals in platelets activated by thrombin (P < 0.05). Treatment of platelets with resveratrol at concentrations of 6.25 and 12.5 microg/ml caused a statistically insignificant increase in the production of O2*- in these cells, as measured by reduction of cytochrome c; however, at higher doses (25, 50 and 100 microg/ml) resveratrol distinctly reduced the generation of O2*- in platelets (P < 0.05). We suggest that free radicals play an important role in the reduced reactivity of blood platelets induced by resveratrol.

Animals↗
PubMed1998

The biostimulatory effect of red laser irradiation on pig blood platelet function.

The molecular mechanisms of laser-induced changes in the cell structure and function are not well known. The authors examined the effects of low-power laser irradiation on unnucleated pig blood platelets. The obtained results showed that laser irradiation (1-5 J) caused in blood platelets lipid peroxidation (measured as thiobarbituric acid reactive substances) and superoxide anion generation, concomitant with the release of adenine nucleotides and proteins from platelets. The maximum platelet response to laser irradiation was observed when doses of 1.8-2 J were used. Our results indicate that red laser irradiation induces: (1) platelet secretory process and the release of substances stored in the specific granules (adenine nucleotides, proteins); and (2) lipid peroxidation partly due to stimulation of endogenous arachidonate and production of its metabolites reacting with thiobarbituric acid.

Adenine Nucleotides↗
PubMed1998

Inhibitory effects of cisplatin and its conjugate with glutathione on blood platelet activity.

Cisplatin (cis -diamminedichloroplatinum II, CDDP) is a widely used chemotherapeutic agent; however, its haematological toxicity may become an important dose-limiting factor. The aim of the present study was to evaluate the effects of cisplatin and its metabolite with glutathione (GS-Pt conjugate) on thrombin-induced platelet aggregation, the secretory process and the arachidonate pathway in vitro. Pre-treatment of platelets with GS-Pt conjugate (60 min, 20 microM) but not with cisplatin alone, caused inhibition of thrombin-induced platelet aggregation. GS-Pt conjugate had also a strong inhibitory effect on the release of proteins and adenine nucleotides from platelet granules. After pre-incubation of platelets with cisplatin and its conjugate, we observed in thrombin-activated platelets, a decreased amount of malonyldialdehyde (a marker of thromboxane A(2) synthesis). We suggest that arachidonate metabolism plays an important role in determining the cytotoxicity of cisplatin.

Journal Article↗
PubMed1998

Modulation of cisplatin toxicity in blood platelets by glutathione depletion.

The effect of a specific inhibitor of gamma-glutamylcysteine synthetase, L-buthionine sulfoximine (BSO), on the action of cisplatin in pig blood platelets was investigated. We show that the effect of BSO, blocking glutathione (GSH) synthesis, on depletion of GSH level in platelets was time and dose dependent (p<0.05). Exposure of blood platelets to BSO reduced not only the cellular GSH content, but diminished also cytotoxicity effects of cisplatin on platelets. Cytotoxic effects of cisplatin were determined by the extent of oxidative stress in these cells, i.e. lipid peroxidation expressed as thiobarbituric acid reactive substances and oxygen free radicals (superoxide anion). The obtained results confirm that the intracellular level of GSH plays an important role in the action of cisplatin on blood platelets.

Animals↗
PubMed1998

Response of blood platelets to Proteus mirabilis lipopolysaccharide.

The effects of the lipopolysaccharide (LPS) of Proteus mirabilis on the production of thiobarbituric acid reactive substances (TBARS) and the generation of superoxide radicals (O2) by pig blood platelets were studied in vitro. The effect of LPS on TBARS formation in platelets was dependent on the concentration of endotoxin. LPS at concentrations above 0.1 microg/10(8) platelets caused the production of TBARS concomitant with the generation of superoxide radicals. The responses of platelets to LPS suggest that endotoxin, like thrombin (a strong platelets agonist), stimulates an enzymatic cascade of platelet arachidonate via cyclooxygenase and produces thromboxane A2 (TXA2) concomitant with malonyldialdehyde (MDA).

Animals↗
PubMed1998

[The role of thrombin in hemostasis].

Thrombin is a serine protease that plays a central role in hemostatic and thrombotic events. The structure, different forms of thrombin, its role in platelet activation and in other cellular effects are reviewed. Two distinct receptors involved in platelet activation induced by alpha-thrombin are presented: a high affinity (GPIb) coupled to phospholipase A2 and a moderate affinity, G protein associated with seven transmembrane domain receptor (STDR) coupled to phospholipase C.

Blood Coagulation↗
PubMed1997

Comparative effects of selenite and selenite on the glutathione-related enzymes activity in pig blood platelets.

The effects of inorganic selenium (Se) compounds (sodium selenite and selenate) on the activities of glutathione-related enzymes (glutathione peroxidase, glutathione-S-transferase [GST] and glutathione reductase [GR]) in pig blood platelets were investigated in vitro. GST activity in blood platelets treated with 10(-4)M of selenite was reduced to 50%, whereas no decrease GST activity was observed after the treatment of platelets with the same dose of selenate. In platelets incubated with physiological doses (10(-7) and 10(-6)M) of Se compounds, the activity of glutathione peroxidase (GSH-Px) was enhanced (about 20%). GR activity after the exposure of platelets to tested Se compounds was unaffected.

Animals↗
PubMed1997

Effect of granulocyte colony stimulating factor on pig blood platelets treated with cisplatin in vitro.

The effects of granulocyte colony stimulating factor (G-CSF) and cisplatin in vitro on the peroxidation of pig platelet endogenous arachidonate were investigated. Estimation of the level of malonyldialdehyde (MDA) after stimulation of platelets with thrombin served as an indicator of this process. MDA concentration was determined by means of a modified method with thiobarbituric acid. The effects of G-CSF on thrombin-induced formation of MDA in platelets was dependent on the concentration and the time of platelet preincubation with this cytokine. In the platelets obtained from the whole blood preincubated with the highest concentration of G-CSF (8 microg/ml), a significant increase of MDA formation was observed (p<0.01). Cisplatin (20 microM) had a strong inhibitory effect on arachidonic acid metabolism in platelets (p<0.001). In the presence of G-CSF (0.8 microg/ml) in incubation medium the inhibitory effect of cisplatin on platelet arachidonate pathway was reduced. The results showed that G-CSF had a protective effect against cisplatin action on platelets.

Animals↗
PubMed1997

[Selenium in the cytotoxicity of cisplatin].

Cisplatin is a widely used chemotherapeutic agent, highly effective in the treatment of various types of human malignancies. The antitumor activity of cisplatin is attributed mainly to its ability to form adducts with DNA. Cisplatin may react with proteins and also with glutathione forming complex GS-Pt. This agent causes haematological, neurological toxicity and changes function of different cells. Recently, is has been reported that administration of sodium selenite reduces cisplatin toxicity without inhibiting the antitumour activity of cisplatin. This review focuses on the mechanism of cisplatin-induced cytotoxicity and the protective role of selenium.

Antineoplastic Agents↗
PubMed1997

Comparative cytotoxicity of cisplatin, sodium selenite and selenium-cisplatin conjugate [(NH3)2Pt(SeO3)]; changes of blood platelet activation.

The cytotoxic effects of a novel compound, conjugate Se-Pt [(NH3)2Pt (SeO3)] on blood platelet function (aggregation, release of adenine nucleotides) were studied. Contrary to the action of cisplatin or selenite alone, [(NH3)2Pt(SeO3)] did not inhibit ADP-induced platelet aggregation, thrombin-induced release of adenine nucleotides from platelets, and had no effect on the metabolism of platelet arachidonate. The tested compound seems to be less toxic than cisplatin alone, and has no effect on blood platelet activation.

Adenine Nucleotides↗