scholarly journals Understanding the Activation of Platelets in Diabetes and Its Modulation by Allyl Methyl Sulfide, an Active Metabolite of Garlic

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Navya Malladi ◽  
Ebin Johny ◽  
Shravan K. Uppulapu ◽  
Vikas Tiwari ◽  
Md Jahangir Alam ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Day Treatment ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Ros Generation ◽  
Methyl Sulfide ◽  
Induced Aggregation

Background. Diabetes mellitus (DM) is a chronic metabolic disorder associated with higher risk of having cardiovascular disease. Platelets play a promising role in the pathogenesis of cardiovascular complications in diabetes. Since last several decades, garlic and its bioactive components are extensively studied in diabetes and its complications. Our aim was to explore the antiplatelet property of allyl methyl sulfide (AMS) focusing on ameliorating platelet activation in diabetes. Method. We used streptozotocin- (STZ-) induced diabetic rats as model for type 1 diabetes. We have evaluated the effect of allyl methyl sulfide on platelet activation by administrating AMS to diabetic rats for 10 weeks. Flow cytometry-based analysis was used to evaluate the platelet activation, platelet aggregation, platelet macrophage interaction, and endogenous ROS generation in the platelets obtained from control, diabetes, and AMS- and aspirin-treated diabetic rats. Results. AMS treatment for 10 weeks effectively reduced the blood glucose levels in diabetic rats. Three weeks of AMS (50 mg/kg/day) treatment did not reduce the activation of platelets but a significant ( p < 0.05 ) decrease was observed after 10 weeks of treatment. Oral administration of AMS significantly ( p < 0.05 ) reduced the baseline and also reduced ADP-induced aggregation of platelets after 3 and 10 weeks of treatment. Furthermore, 10 weeks of AMS treatment in diabetic rats attenuated the endogenous ROS content ( p < 0.05 ) of platelets and platelet macrophage interactions. The inhibition of platelet activation in diabetic rats after AMS treatment was comparable with aspirin treatment (30 mg/kg/day). Conclusion. We observed an inhibitory effect of allyl methyl sulfide on platelet aggregation, platelet activation, platelet macrophage interaction, and increased ROS levels in type 1 diabetes. Our data suggests that AMS can be useful to control cardiovascular complication in diabetes via inhibition of platelet activation.

scholarly journals Influence of hyperinsulinemic – hypoglycemic clamp on induced platelet aggregation, activity of physiological anticoagulants and von Willebrand factor in patients with type I diabetes

2018 ◽  
Vol 21 (2) ◽  
pp. 84-91
Author(s):  
Iwona R. Jarek-Martynowa ◽  
Mikhail Y. Martynov ◽  
Karina G. Sarkisova ◽  
Ekaterina O. Koksharova ◽  
Ekaterina E. Mishina ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Protein C ◽  
Protein S ◽  
Normal Limits ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Protein S Activity

Background. Intensive glycaemic control in patients with type 1 diabetes may lead to hypoglycaemia and thus increase the risk of cardiovascular and cerebrovascular events. Platelet activation and/or decreased activity of physiological anticoagulants during hypoglycaemia may play a role in the development of cardiovascular or cerebrovascular complications. Aims. To investigate induced platelet activity, the activity of physiological anticoagulants, and the von Wil-lebrand factor in patients with type 1 diabetes with the hyperinsulinaemichypoglycaemic clamp. Materials and methods. We examined 11 patients with type 1 diabetes without macro- and micro-vascular complications (6 males, 5 females, mean age 23.7 5.6 years, A1C 9.7 2.3%). Induced platelet aggregation, physiological anticoagulants (Protein S, Protein C, AT III) and the von Willebrand factor were studied at hyperglycaemic, euglycaemic, and hypoglycaemic stages during use of a hyperinsulinaemic (1 mU/kg/min) hypoglycaemic clamp. Results. Platelet aggregation to all agonists increased significantly during the hypoglycaemic stage, compared with the euglycaemic or hyperglycaemic stages. There was no difference in platelet aggregation between the euglycaemic and hyperglycaemic stages. Platelet aggregation to all agonists increased during the hypoglycaemic stage compared with the hyperglycaemic period: thrombin23.9%, ADP30.6%, arachidonic acid30.9%, collagen69.4% and ristocetin70.8%. During hypoglycaemia aggregation to ADP, arachidonic acid and collagen remained within normal limits (upper quartile); aggregation to thrombin was significantly above normal limits and aggregation to ristocetin remained significantly below lower limits. Protein S activity was significantly increased during hypoglycaemia compared with euglycaemia (p = 0.046) and hyperglycaemia (p = 0.046). Antithrombin-III activity decreased significantly at the euglycaemic and hypoglycaemic stages, compared with the hyperglycaemic period, but still remained significantly elevated above the upper threshold. Protein C and vWf activity did not change significantly. Conclusions. In patients with type 1 diabetes platelet aggregation and protein S activity increases significantly at the hypoglycaemic stage of the hyperinsulinaemichypoglycaemic clamp. Platelet activation is directly caused by hypoglycaemia and not by decreasing glucose levels. Increased protein S activity is a compensatory response to platelet activation.

In vitro effect of D-myo-inositol 1,2,6-trisphosphate (PP-56) on aggregation of platelets from normal and diabetic rats: relationship to malondialdehyde release and phosphoinositide pathway

1994 ◽  
Vol 72 (6) ◽  
pp. 644-649 ◽  
Author(s):  
J. C. Ruf ◽  
M. Ciavatti ◽  
T. Gustafsson ◽  
S. Renaud
Keyword(s):  
Platelet Aggregation ◽  
Inositol Phosphates ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Term Administration ◽  
In Vitro Effects ◽  
Vitro Effect ◽  
Induced Aggregation

In the present study, we investigated the in vitro effects of D-myo-inositol 1,2,6-trisphosphate (PP-56) on platelets from normal and streptozotocin-induced diabetic rats. PP-56 markedly inhibited aggregation, in a dose-related manner, when added in vitro, more efficiently with thrombin- than with ADP-induced aggregation and, after 90 min incubation, more in diabetic than in normal platelets. The PP-56 platelet inhibitory effect seems to be related to its phosphate content. PP-56 blocked the release of malondialdehyde from erythrocytes, but to the same extent in normal and diabetic rats. PP-56, after 20 min incubation, restored the platelet phosphoinositide turnover, which was significantly modified in diabetic rats. This last observation could explain at least part of the specificity of PP-56 for normalizing platelet aggregation in diabetic animals after long-term administration in vivo.Key words: inositol phosphates, platelet aggregation, streptozotocin-induced diabetic rats.

On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Marked Enhancement ◽  
Matrix Bound ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

Opposite Effect of Lysine on Platelet Aggregation Induced by Arachidonate and by Other Aggregants

1982 ◽  
Vol 48 (01) ◽  
pp. 078-083 ◽  
Author(s):  
C Ts'ao ◽  
S J Hart ◽  
D V Krajewski ◽  
P G Sorensen
Keyword(s):  
Platelet Aggregation ◽  
Secondary Phase ◽  
Aminocaproic Acid ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Primary Phase ◽  
High Doses ◽  
The Many ◽  
Induced Aggregation

SummaryEarlier, we found that ε-aminocaproic acid (EACA) inhibited human platelet aggregation induced by adenosine diphosphate (ADP) and collagen, but not aggregation by arachidonic acid (AA). Since EACA is structurally similar to lysine, yet these two agents exhibit vast difference in their antifibrinolytic activities, we chose to study the effect of lysine on platelet aggregation. We used L-lysine-HCl in these studies because of its high solubility in aqueous solutions while causing no change in pH when added to human plasma. With lysine, we repeatedly found inhibition of ADP-, collagen- and ristocetin-induced aggregation, but potentiation of AA-induced aggregation. Both the inhibitory and potentiation effects were dose-dependent. Low doses of lysine inhibited the secondary phase of aggregation; high doses of it also inhibited the primary phase of aggregation. Potentiation of AA-induced aggregation was accompanied by increased release of serotonin and formation of malondialdehyde. These effects were not confined to human platelets; rat platelets were similarly affected. Platelets, exposed to lysine and then washed and resuspended in an artificial medium not containing lysine, remained hypersensitive to AA, but no longer showed decreased aggregation by collagen. Comparing the effects of lysine with equimolar concentrations of sucrose, EACA, and α-amino-n-butyric acid, we attribute the potent inhibitory effect of lysine to either the excess positive charge or H+ and C1− ions. The -NH2 group on the α-carbon on lysine appears to be the determining factor for the potentiation effect; the effect seems to be exerted on the cyclooxygenase level of AA metabolism. Lysine and other chemicals with platelet-affecting properties similar to lysine may be used as a tool for the study of the many aspects of a platelet aggregation reaction.

Inhibition of Human Platelet Aggregation by the Proteolytic Effect of Streptokinase (SK). Role of the Factor VIII Related Antigen

1975 ◽  
Author(s):  
R. Castillo ◽  
S. Maragall ◽  
J. A. Guisasola ◽  
F. Casals ◽  
C. Ruiz ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Factor Viii Related Antigen ◽  
Human Factor Viii ◽  
Induced Aggregation

Defective ADP-induced platelet aggregation has been observed in patients treated with streptokinase. This same effect appears “in vitro” when adding SK to platelet rich plasma (PRP). Classic hemophilia and normal platelet poor plasmas (PPP) treated with SK inhibit the aggregation of washed platelets; plasmin-treated normal human serum also shows an inhibitory effect on platelet aggregation. However, von Willebrand SK-treated plasmas do not inhibit the aggregation of washed platelets. The same results appear when plasmas are previously treated with a rabbit antibody to human factor VIII.This confirms that the antiaggregating effect is mainly linked to the digested factor VIII related antigen.The inhibition of ADP-induced platelet aggregation has been proved in gel filtration-isolated and washed platelets from SK-treated PRP.Defective ristocetin-induced platelet aggregation has also been observed- This action does not appear in washed platelets from SK-treated PRP in presence of normal PPP, but it does in presence of SK-treated PPP, which suggests that the inhibition of the ristocetin-induced aggregation is due to the lack of factor VIII and not to the factor VIII-related products.Heparin, either “in vivo” or “in vitro”, has corrected the antiaggregating effect of SK.

Ex vivo evaluation of anti-GPVI antibody in Cynomolgus monkeys: Dissociation between anti-platelet aggregatory effect and bleeding time

2006 ◽  
Vol 96 (08) ◽  
pp. 167-175 ◽  
Author(s):  
Yutaka Matsumoto ◽  
Hisao Takizawa ◽  
Kazuhiro Nakama ◽  
Xiaoqi Gong ◽  
Yoshihisa Yamada ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Inhibitory Effect ◽  
Bleeding Tendency ◽  
Fab Fragment ◽  
Dose Escalation Study ◽  
Cynomolgus Monkeys ◽  
Induced Aggregation

SummaryRecent progress in the understanding of thrombus formation has suggested an important role of glycoprotein (GP)VI. In contrast to its pivotal role in collagen-induced platelet activation, it has been suggested that its blockade does not induce massive bleeding tendency. To demonstrate the dissociation between inhibitory effect on platelet aggregation and bleeding by GPVI blockade, we examined the effects of Fab fragment of OM2, an anti-human GPVI monoclonal antibody on ex vivo collagen-induced platelet aggregation and skin bleeding time after intravenous injection in cynomolgus monkeys. In a dose-escalation study, OM2 potently (>80%) inhibited collagen-induced platelet aggregation at the cumulative dose of 0. 2 mg/kg with a slight prolongation of bleeding time (1. 3 times baseline value). Furthermore, at 18. 8 mg/kg, the highest dose tested, prolongation of bleeding time was still mild (1. 9 times). In contrast, abciximab, Fab fragment of anti-GPIIb/IIIa antibody prolonged bleeding time by 5. 0 times at 0. 35 mg/kg, the lowest effective dose on platelet aggregation. Ina pharmacodynamic study,a bolus injection of OM2 at 0. 4 mg/kg produced potent inhibition of collagen-induced aggregation up to six hours after injection, showing longer half-life than that of abciximab. The injection of OM2 Fab did not induce thrombocytopenia and GPVI depletion in monkeys. These results suggest that blockade of GPVI by antibody can exerta potent inhibitory effect on collagen-induced platelet aggregation with a milder prolongation of bleeding time than blockade of GPIIb/IIIa. This study indicates that OM2 has the potential to be developed as a new class of therapeutic tool.

scholarly journals Cigarette Smoke Extract Inhibits Platelet Aggregation by Suppressing Cyclooxygenase Activity

TH Open ◽  
2017 ◽  
Vol 01 (02) ◽  
pp. e122-e129
Author(s):  
Hitoshi Kashiwagi ◽  
Koh-ichi Yuhki ◽  
Yoshitaka Imamichi ◽  
Fumiaki Kojima ◽  
Shima Kumei ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Cigarette Smoke ◽  
Platelet Function ◽  
Inhibitory Effect ◽  
Cigarette Smoke Extract ◽  
Human Platelets ◽  
Receptor Subtypes ◽  
Ic50 Value ◽  
Induced Aggregation ◽  
Cox 1

AbstractThe results of studies that were performed to determine whether cigarette smoking affects platelet function have been controversial, and the effects of nicotine- and tar-free cigarette smoke extract (CSE) on platelet function remain to be determined. The aim of this study was to determine the effect of CSE on platelet aggregation and to clarify the mechanism by which CSE affects platelet function. CSE inhibited murine platelet aggregation induced by 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619), a thromboxane (TX) A2 receptor agonist, and that induced by collagen with respective IC50 values of 1.05 ± 0.14% and 1.34 ± 0.19%. A similar inhibitory action of CSE was also observed in human platelets. CSE inhibited arachidonic acid–induced TXA2 production in murine platelets with an IC50 value of 7.32 ± 2.00%. Accordingly, the inhibitory effect of CSE on collagen-induced aggregation was significantly blunted in platelets lacking the TXA2 receptor compared with the inhibitory effect in control platelets. In contrast, the antiplatelet effects of CSE in platelets lacking each inhibitory prostanoid receptor, prostaglandin (PG) I2 receptor and PGE2 receptor subtypes EP2 and EP4, were not significantly different from the effects in respective control platelets. Among the enzymes responsible for TXA2 production in platelets, the activity of cyclooxygenase (COX)-1 was inhibited by CSE with an IC50 value of 1.07 ± 0.15% in an uncompetitive manner. In contrast, the activity of TX synthase was enhanced by CSE. The results indicate that CSE inhibits COX-1 activity and thereby decreases TXA2 production in platelets, leading to inhibition of platelet aggregation.

COMPARISON OF THE PLATELET AGGREGATION INDUCED BY THREE THROMBIN-LIKE ENZYMES OF SNAKE VENOMS AND THROMBIN

1987 ◽  
Author(s):  
C M Teng ◽  
F N Ko
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Creatine Phosphokinase ◽  
Antithrombin Iii ◽  
Atp Release ◽  
Creatine Phosphate ◽  
Snake Venoms ◽  
Rabbit Platelets ◽  
Bothrops Atrox ◽  
Induced Aggregation

Acutin was isolated from Agkistrodon acutus venom and batroxobin and thrombocytin were isolated from Bothrops atrox venom. These three thrombin-like enzymes had different specificity for platelet activation and fibrinogen clotting. The clotting activities were 700, 170 and 7 μ/mg for batroxobin, acutin and thrombocytin, respectively. They induced aggregation and ATP release of washed rabbit platelets. The aggregating activities were 102, 104 and 105 times less than that of thrombin for thrombocytin, acutin and batroxobin, respectively basing on the clotting unit. The platelet -activating potency was correlated with their effectiveness on the retractility and elasticity of the clots. Platelet aggregation induced by thrombin or thrombocytin could be inhibited by heparin with antithrombin III while that by acutin or batroxobin could not. The thrombin-like enzymes did not induce aggregation of thrombin-degranulated platelets even fibrinogen was added. Indomethacin showed weak inhibition on the aggregation while the ADP - scavenging system, creatine phosphate/creatine phosphokinase, or apyrase inhibited the aggregation induced by the three thrombin-like enzymes but not that by thrombin. In the presence of EGTA, only thrombin could induce ATP release from platelets. It is concluded that the aggregation induced by thrombin-like enzymes is different from that of thrombin and mainly due to ADP released from platelets.

scholarly journals Baccharis trimera (Carqueja) Improves Metabolic and Redox Status in an Experimental Model of Type 1 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Natália Nogueira do Nascimento Kaut ◽  
Ana Carolina Silveira Rabelo ◽  
Glaucy Rodrigues Araujo ◽  
Jason Guy Taylor ◽  
Marcelo Eustáquio Silva ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Diabetic Rats ◽  
Female Rats ◽  
Redox Stress ◽  
Carbonyl Protein ◽  
Hydroethanolic Extract ◽  
Baccharis Trimera

Diabetes mellitus is a metabolic disorder that causes severe complications due to the increased oxidative stress induced by disease. Many plants are popularly used in the treatment of diabetes, e.g., Baccharis trimera (carqueja). The aim of this study was to explore the potential application of the B. trimera hydroethanolic extract in preventing redox stress induced by diabetes and its hypoglycemic properties. Experiments were conducted with 48 female rats, divided into 6 groups, named C (control), C600 (control + extract 600 mg/kg), C1200 (control + extract 1200 mg/kg), D (diabetic), D600 (diabetic + 600 mg/kg), and D1200 (diabetic + 1200 mg/kg). Type 1 diabetes was induced with alloxan, and the animals presented hyperglycemia and reduction in insulin and body weight. After seven days of experimentation, the nontreated diabetic group showed changes in biochemical parameters (urea, triacylglycerol, alanine aminotransferase, and aspartate aminotransferase) and increased carbonyl protein levels. Regarding the antioxidant enzymes, an increase in superoxide dismutase activity was observed but in comparison a decrease in catalase and glutathione peroxidase activity was noted which suggests that diabetic rats suffered redox stress. In addition, the mRNA of superoxide dismutase, catalase, and glutathione peroxidase enzymes were altered. Treatment of diabetic rats with B. trimera extract resulted in an improved glycemic profile and liver function, decreased oxidative damage, and altered the expression of mRNA of the antioxidants enzymes. These results together suggest that B. trimera hydroethanolic extract has a protective effect against diabetes.

Prostaglandins and Platelet Function in Diabetes

1979 ◽  
Author(s):  
J. García-Conde ◽  
J.A. Amado ◽  
J. Merino ◽  
I. Benet
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Diabetic Group ◽  
Diabetic Patients ◽  
Prostaglandin I2 ◽  
Induced Aggregation ◽  
Normal Controls

We have studied platelet aggregation induced by 0,5 mM. Araquidonic acid (AA) addition to platelet-rich-plasma (PRP) from 21 insulin treated diabetic patients and in 21 non-diabetic controls. The velocity of aggregation was significantly higher in the diabetic group. There was no differences in the velocity of aggregation in patients with or without retinopathy.The incubation of PRP of normal subjects at 37- during 5 minutes with 5,8 10-4 M. Imidazole changed the pattern of aggregation: The velocity of aggregation was slower and appeared a wave of disaggregation. Imida zole had not effect on aggregation in the diabetic group. This data add support to the findings published by COLWLLL showing that platelets from diabetics have hyperactive AA metabolism. Prostaglandin I2 (PGI2) obtained from rat aorta shows an inhibitory effect on ADP or AA induced aggregation. This effect is less marked in diabetic PRP than in PRP of normal controls. PGI2 release in platelet-poor-plasma from diabetics is normal. This can represent a resistance ot diabetic platelet to the anti aggregating effect of PGI 2. A similar finding was also appreciated with the PGE1 in three out of six patients so tar stu

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