scholarly journals Lipid peroxidation, prostacyclin and thromboxane A2 in pigs depleted of vitamin E and selenium and supplemented with linseed oil

1995 ◽  
Vol 74 (3) ◽  
pp. 369-380 ◽  
Author(s):  
Maeve R. Nolan ◽  
Seamus Kennedy ◽  
W. John Blanchflower ◽  
D. Glenn Kennedy
Keyword(s):  
Lipid Peroxidation ◽  
Arachidonic Acid ◽  
Vitamin E ◽  
Platelet Aggregation ◽  
Plasma Concentration ◽  
Linseed Oil ◽  
Thromboxane A2 ◽  
Dietary Factors ◽  
Biochemical Effects ◽  
Skeletal Myopathy

In a 2×2 balanced factorial experiment the biochemical effects on pigs of two dietary factors were investigated. The first factor was α-tocopherol and Se supplementation and the second factor was supplementation with α-tocopherol-stripped linseed oil. In pigs fed on diets depleted of α-tocopherol and Se, increases in concentrations of markers of lipid peroxidation (4-hydroxynonenal and hexanal) were observed. However, skeletal myopathy was only observed in those pigs fed on diets depleted of α-tocopherol and Se and supplemented with oil. In those pigs, increased lipid peroxidation was observed in heart and supraspinatus muscle. The plasma concentration of thromboxane B2 was increased in pigs fed on diets depleted of α-tocopherol and Se, suggesting an increased tendency towards platelet aggregation. However, this change was reversed in pigs depleted of α-tocopherol and Se, but supplemented with oil. This may have been a consequence of loss of arachidonic acid, the substrate for thromboxane formation, as a result of lipid peroxidation.

In Vitro Incorporation and Metabolism of Icosapentaenoic and Docosahexaenoic Acids in Human Platelets - Effect on Aggregation

1986 ◽  
Vol 56 (01) ◽  
pp. 057-062 ◽  
Author(s):  
Martine Croset ◽  
M Lagarde
Keyword(s):  
Arachidonic Acid ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Fatty Acid Distribution ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Aggregation Response ◽  
Docosahexaenoic Acids ◽  
Membrane Level

SummaryWashed human platelets were pre-loaded with icosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or EPA + DHA and tested for their aggregation response in comparison with control platelets. In fatty acid-rich platelets, an inhibition of the aggregation could be observed when induced by thrombin, collagen or U-46619. The strongest inhibition was observed with DHA-rich platelets and it was reduced when DHA was incorporated in the presence of EPA.Study of fatty acid distribution in cell lipids after loading showed that around 90% of EPA or DHA taken up was acylated into phospholipids and a very small amount (less than 2%) remained in their free and hydroxylated forms. DHA was more efficiently acylated into phosphatidylethanolamine (PE) than into phosphatidylinositol (PI) in contrast to what observed with EPA, and both acids were preferentially incorporated into phosphatidylcholine (PC). EPA inhibited total incorporation of DHA and increased its relative acylation into PE at the expense of PC. In contrast, DHA did not affect the acylation of EPA. Upon stimulation with, thrombin, EPA was liberated from phospholipids and oxygenated (as judged by the formation of its monohydroxy derivative) whereas DHA was much less metabolized, although consistently transferred into PE.It is concluded that EPA and DHA might affect platelet aggregation via different mechanisms when pre-loaded in phospholipids. Whereas EPA is known to alter thromboxane A2 metabolism from endogenous arachidonic acid, by competing with it, DHA might act directly at the membrane level for inhibiting aggregation.

Diabetic Retinopathy And Thromboxane Like Substance

1981 ◽  
Author(s):  
M A Lazzari ◽  
M Gimeno ◽  
N M Sutton ◽  
J R Lopez
Keyword(s):  
Diabetes Mellitus ◽  
Arachidonic Acid ◽  
Diabetic Retinopathy ◽  
Risk Factor ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Thromboxane A2 ◽  
Initial Step ◽  
Platelet Activity

Diabetes Mellitus (DM) is a risk factor in the development of vasculopathies and its complications. It produces also its own microangiopathy. Evidence was reported of increased platelet activity in DM in different assays. Platelets aggregation and the arachidonic cycle could play a key role in the increased tendency to thrombosis. A disorder of ratio TXA2/PGI2, two opposing prostaglandin derivatives, could be the initial step. We intended to evaluate a thromboxane like substance (TLS) produced from platelet rich plasma (PRP) and to compare between normals and diabetic retinopathy (DR) patients. TLS was measured in 16 controls and 16 patients. Assay was done with the aggregating activity developed in PRP (considered TLS) after addition of arachidonic acid (f.c. 2 mM). The supernatant of the PRP (100 μl) was taken 40 sec. after the aggregation started and were added to a normal PRP treated with aspirin (f.c. 40 μl/ml) adjusted to 250.000 - 300.000 pl/μl and the degree of platelet aggregation measured in a Chrono Log Aggregometer. TLS was inactivated after its incubation during 2 min. at 37°C. This finding suggests this activity is due to TXA2.The results obtained (expressed in % of platelet aggregation) were: controls x 16.37% ± 6.28 and DR x 36.00% ± 9.72.The increase detected in the DR group supports previous experimental reports suggesting the role of the thromboxane A2 in vaso occlusive complication of diabetes mellitus.

Lack Of Inhibition Of Thromboxane Production Despite Inhibition Of Platelet Function By 1,3-Bis(2 Chloroethyl)-1-Nitrosourea (BCNU)

1981 ◽  
Author(s):  
R McKenna ◽  
T Ahmad ◽  
A Prancan ◽  
D Simon ◽  
H Frischer
Keyword(s):  
Arachidonic Acid ◽  
Oxygen Consumption ◽  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Platelet Function ◽  
Human Platelet ◽  
Thromboxane A2 ◽  
Rabbit Aorta ◽  
Thromboxane Production ◽  
Platelet Thromboxane

We have previously shown that BCNU inhibits human platelet glutathione reductase (GSSG-R) prior to inhibiting platelet function; since thromboxane production is important in platelet function, we evaluated the effect of BCNU induced inhibition of GSSG-R on platelet thromboxane production.Control platelet GSSG-R activity was 0.091 ]jmoles NAD(P)H oxidized min-1lmg-1 protein at 37°C (±0.015 S.D.; n=9); inhibition was detectable at 10-7M% BCNU (70% of control) with a >90% inhibition at and above 10-5M BCNU. Platelet aggregation in response to 1.5×10-3M Arachidonic acid (AA), 10 μM epinephrine, 6 μg/ml equine collagen and 3 μM ADP were inhibited at 10-5M BCNU and abolished at 10-4 BCNU.BCNU (10-3M) did not affect the increase in oxygen consumption induced by AA. Using the rabbit aorta superfusion bioassay for thromboxane A2 (TXA2), threshold concentrations of AA in 10-5 and 10-4 BCNU platelets resulted in an increased measure of aortic tension 13.5 ± 9.4 mm S.D. (n=6) and 23.2 ± 9.5 mm respectively, compared with control values of 4.5 ± 2.4. Acetylsalicylic acid (5 × l0-4M) inhibited the contraction: 1.7 ± 1.1 (n=5). The conversion of 14C AA to thromboxane B2 (TXB2) and PGE2, as measured by radio TLC, was not decreased in BCNU treated platelets. There is a significant increase in TXB2 (p<0.05;n=4) and in the ratio of TXB2:PGE2 in platelets treated with 10-4M BCNU and 10-3M imidazole when compared to platelets treated with imidazole alone.In conclusion BCNU induced inhibition of platelet GSSG-R and platelet function occurs despite preservation of thromboxane production

scholarly journals Inhibitory and synergistic effects of natural olive phenols on human platelet aggregation and lipid peroxidation of microsomes from vitamin E-deficient rats

2014 ◽  
Vol 54 (8) ◽  
pp. 1287-1295 ◽  
Author(s):  
Fátima Rubio-Senent ◽  
Baukje de Roos ◽  
Garry Duthie ◽  
Juan Fernández-Bolaños ◽  
Guillermo Rodríguez-Gutiérrez
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Platelet Aggregation ◽  
Human Platelet ◽  
Synergistic Effects ◽  
Human Platelet Aggregation

ADRENALINE (ADR) INTERACTIONS WITH THROMBIN AND COLLAGEN -EFFECTS ON PLATELET ARACHIDONATE RELEASE AND 5HT SECRETION AND ROLE OF ENDOGENOUSLY FORMED THROMBOXANE A2 (TxA2)

1987 ◽  
Author(s):  
Y Patel ◽  
S Krishnamurthi ◽  
V V Kakkar
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenylate Cyclase ◽  
Synergistic Effects ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Presence And Absence ◽  
Pre Treatment ◽  
Arachidonate Release

We have examined the effect of combinations of ADR + thrombin (T) and ADR + collagen (C) on platelet arachidonate release and 5HT secretion, and assessed the role of endogenously formed TxA2 on these responses using indomethacin (I). Washed, human platelets prelabelled with [3H]-arachidonic acid (AA) or [14C]-5HT were used, ADR was added 10 sec before T or C and the reaction was terminated 3 min later. In the range 1-100μM, ADR induced no detectable aggregation or 5HT secretion but potentiated platelet aggregation when added with sub-threshold concentrations of T or C, which on their own induced no aggregation. At 2-4 fold higher concentrations of T and C (threshold for 5HT secretion), 5HT secretion and AA/TXB2 release were also potentiated by ADR (1-10μM) by 30-50%. Pre-treatment of platelets with I (10μM) abolished threshold T and C-induced 5HT secretion, as well as its potentiation by ADR. However, approximately 2-fold and 5-fold higher concentrations of T and C respectively were able to induce 'I-insensitive'secretion, which was further potentiated by ADR. In I-treated platelets, C-induced AA release and its potentiation by ADR were also abolished suggesting a role for endogenously formed TxA2 This was confirmed by addition of the TxA2 mimetic, U46619 (0.3μM), which potentiated C-induced AA release in the presence and absence of ADR, even though it induced no AA release on its own or, in combination with ADR alone in the absence of collagen. The latter suggests agonist specificity regarding the ability of TxA2 to synergistically stimulate AA release. Finally, unstirred platelets in PRP pre-incubated with ADR (10μM) for 120 min lost their responsiveness to ADR, when eventually stirred; however, these 'ADR-desensitised' platelets when washed and resuspended, were able to demonstrate synergistic effects on secretion when stimulated with ADR+T or ADR+C. This is analogous to the previously demonstrated ability of ADR to inhibit adenylate cyclase even in 'ADR-desensitised' platelets and re-inforces the separation regarding the mechanisms underlying the various effects of ADR on platelets.

A Study of Intravascular Platelet Aggregation in the Rat

1979 ◽  
Author(s):  
G. G. Duncan ◽  
G. M. Smith
Keyword(s):  
Arachidonic Acid ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Residual Response ◽  
Induced Aggregation ◽  
Anaesthetized Rat

Intravascular platelet aggregation can be studied by measuring the fall in the circulating platelet count induced by aggregating agents in anaesthetized animals. The Technicon Auto-counter was modified and connected via a double cannula to an anaesthetized rat to give a continuous count of the number of circulating platelets (1). Adenosine diphosphate (ADP), Collagen, Arachidonic acid (AA) and 5-Hydroxytryptamine (5-HT) were given at 15 minute intervals over a period of 2-3 hours. Aspirin (10 mg/Kg IV ) and Indomethacin (1-8 mg/Kg IV) partially inhibited collagen-induced aggregation and Indomethacin (2 mg/Kg IV) completely inhibited AA-induced aggregation. Adenosine (0.25 mg/min) inhibited the ADP-induced aggregation but did not inhibit aggregation produced by collagen or the residual response to collagen that remains after the addition of indomethacin.Reproducible responses to ADP and collagen were obtained but responses to AA and 5-HT were not reliable. Collagen-induced aggregation is thought to be mediated by the liberation of ADP, 5-HT and the formation of prostaglandin (PG ) endoperoxides and thromboxane A2. This study has shown that collagen-induced aggregation is reduced by inhibition of PG synthesis but the involvement of ADP or 5-HT could not be shown.

Effect of Picotamide on Platelet Aggregation and on Thromboxane A2 Production In Vivo

1991 ◽  
Vol 65 (03) ◽  
pp. 312-316 ◽  
Author(s):  
P Minuz ◽  
C Lechi ◽  
E Arosio ◽  
P Guzzo ◽  
M Zannoni ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Single Dose ◽  
Platelet Aggregation ◽  
Urinary Excretion ◽  
Ex Vivo ◽  
Thromboxane A2 ◽  
Normal Subjects ◽  
Dose Aspirin ◽  
Induced Aggregation

SummaryEffects of picotamide (900 mg in 3 oral administrations for 7 days) on ex vivo and in vivo platelet T×A2 production and on platelet aggregation wpre evaluated in 8 patients with peripheral arteriopathy and in 8 normal subjects. Picotamide significantly reduced ADP-induced platelet aggregation, but had no effect on that induced by arachidonic acid or the thromboxane analogue U46619. Though ex vivo platelet T×A2 production (T×B2 concentration after arachidonic-acid-induced aggregation) was reduced from 946 ± 141 (mean ± SD) to 285 ± 91 ng/ml in controls and from 1515 ± 673 to 732 ± 420 ng/ml in patients with arteriopathy, there was no effect on urinary excretion of 2,3-dinor-T×B2 (in vivo indicator of platelet T×A2 production), or on in vivo PGI2 production (urinary excretion of 6-keto-PGF1α and 2,3-dinor-6-keto-PGF1α). In the same subjects, single-dose aspirin reduced ex vivo T×B2 production by at least 98% and 2,3-dinor-T×B2 excretion from 116.7 ± 61.4 to 32.6 ± 17.0 nglg creatinine in control subjects, and from 156.3 ± 66.1 to 59.1 ± 19.2 ng/g creatinine in patients with peripheral arteriopathy. Our data suggest that inhibition of platelet T×A2 production in vivo may not be picotamide’s main mechanism of action.

scholarly journals Hydrogen Peroxide Is Involved in Collagen-Induced Platelet Activation

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Pasquale Pignatelli ◽  
Fabio M. Pulcinelli ◽  
Luisa Lenti ◽  
Pier Paolo Gazzaniga ◽  
Francesco Violi
Keyword(s):  
Hydrogen Peroxide ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Phospholipase C ◽  
Platelet Activation ◽  
Acid Metabolism ◽  
Thromboxane A2 ◽  
Arachidonic Acid Metabolism ◽  
H2o2 Production ◽  
High Concentrations

Abstract In this study, we investigated whether (1) collagen-induced platelet aggregation is associated with a burst of H2O2, (2) this oxidant species is involved in the activation of platelets, and (3) the pathways of platelet activation are stimulated by H2O2. Collagen-induced platelet aggregation was associated with production of H2O2, which was abolished by catalase, an enzyme that destroys H2O2. H2O2 production was not observed when ADP or thrombin were used as agonists. Catalase inhibited dose-dependently thromboxane A2 production, release of arachidonic acid from platelet membrane, and Inositol 1,4,5P3 (IP3) formation. In aspirin-treated platelets stimulated with high concentrations of collagen, catalase inhibited platelet aggregation, calcium mobilization, and IP3 production. This study suggests that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.

scholarly journals The inhibitory effects of exogenous arachidonic acid on rabbit platelet aggregation and the release reaction

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1179-1187
Author(s):  
M Cattaneo ◽  
RL Kinlough-Rathbone ◽  
DW Perry ◽  
A Chahil ◽  
JD Vickers ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Thromboxane A2 ◽  
Nordihydroguaiaretic Acid ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
General Effect ◽  
Lipoxygenase Pathway ◽  
Free Arachidonic Acid

Although arachidonic acid causes rabbit platelet aggregation and the release of granule contents in suspensions of washed platelets when used in concentrations of approximately 50–300 microM, higher concentrations (500 microM) cause neither aggregation nor release. Suspensions of platelets from rabbits wee exposed to arachidonic acid (250 microM) for 15 min, allowed to recover in the presence of PGE1 for 30 min, washed, and resuspended; in some experiments, the platelets were treated with aspirin before being exposed to arachidonic acid. Aggregation of platelets pretreated with arachidonic acid was inhibited in response to ADP; this effect was greater with the non-aspirin- treated platelets and persisted for at least 4 hr after resuspension. The association of 125I-fibrinogen with the platelets as a result of ADP stimulation was also inhibited. Aggregation and release of granule contents in response to collagen and low concentrations of thrombin was inhibited, but the inhibition could be overcome by higher concentrations. Thrombin induced further release of granule contents from platelets exposed to arachidonic acid without pretreatment with aspirin. Platelets that had been exposed to arachidonic acid, either with or without pretreatment with aspirin, did not aggregate or undergo further release upon stimulation with arachidonic acid after they were washed and resuspended. Inhibition of the lipoxygenase pathway with eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA) did not affect the inhibition caused by arachidonic acid, so it is unlikely that a product of this pathway is responsible for the inhibition. Mixing experiments indicated that the pretreated platelets did not form a thromboxane-A2-like activity, and that they were unresponsive to aggregation and release induced by products formed from arachidonic acid. Experiments with 3H-arachidonic acid showed that after 45 min of incubation with platelets, only 1.1% of the 3H-arachidonic acid remained as free arachidonic acid in the platelets. Although cyclic-AMP was slightly increased 1 min after the addition of arachidonic acid, the cyclic-AMP concentration was the same as that of control platelets after the platelets were washed and resuspended, indicating that increased cyclic-AMP is not likely to be responsible for the persistent inhibitory effect. Thus, the inhibitory effect of pretreatment with arachidonic acid is a general effect on responses to a variety of aggregating agents that act through different mechanisms, and the inhibition is not related to thromboxane-A2 formation. The possibility of membrane perturbation resulting in the unavailability of receptors may explain the persistent inhibitory effect, but the responsible reactions have not been identified.

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