scholarly journals Effect of l-Carnitine on Acetyl-CoA Content and Activity of Blood Platelets in Healthy and Diabetic Persons

2005 ◽  
Vol 51 (9) ◽  
pp. 1673-1682 ◽  
Author(s):  
Anna Michno ◽  
Anna Raszeja-Specht ◽  
Agnieszka Jankowska-Kulawy ◽  
Tadeusz Pawełczyk ◽  
Andrzej Szutowicz

Abstract Background: Excessive blood platelet activity contributes to vascular complications in diabetic persons. Increased acetyl-CoA in platelets from diabetic persons has been suggested to be a cause of this hyperactivity. We therefore investigated whether l-carnitine, which up-regulates metabolism of acetyl-CoA in muscles and brain, may affect platelet function in healthy and diabetic individuals. Methods: We obtained platelets from healthy and diabetic persons and measured acetyl-CoA concentrations, malonyl dialdehyde (MDA) synthesis, and platelet aggregation in the absence and presence of l-carnitine. Activities of selected enzymes involved in glucose and acetyl-CoA metabolism were also assessed. Results: Fasting glucose, fructosamine, and hemoglobin A1c were present in significantly higher amounts in the blood of diabetic patients than in healthy individuals. Activities of carnitine acetyltransferase, glucose-6-phosphate dehydrogenase, oxoglutarate dehydrogenase, and fatty acid synthase were 17%–62% higher in platelets from diabetic patients. Mitochondrial acetyl-CoA was increased by 98% in platelets from diabetic patients, MDA synthesis was increased by 73%, and platelet aggregation by 60%. l-Carnitine had no or only a slight effect on these indices in platelets from healthy individuals, but in platelets from diabetic patients, l-carnitine caused a 99% increase in acetyl-CoA in the cytoplasmic compartment along with increases in MDA synthesis and platelet aggregation. Conclusions: Excessive platelet activity in persons with diabetes may result from increased acetyl-CoA, which apparently increases synthesis of lipid activators of platelet function. l-Carnitine may aggravate platelet hyperactivity in diabetic persons by increasing the provision of surplus acetyl-CoA to the cytoplasmic compartment.

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Gratia Tangkuman

Abstract: Diabetes melitus is a main medical problem around the world. WHO estimated that in 2000 there were 171 milion people with diabetes around the world and in 2030 there will be 366 million people. In diabetic patients, there are dysfunctions of platelet function caused microangiopati, macroangiopati, and platelet reactivity. Dysfunction of platelet function are associated with vascular complications of diabetes melitus. This study used an observational analytic method using comparative hypothesis test. This study was conducted to 30 diabetic patients, 15 patients have vascular complications while the other 15 have no vascular complications. Those patients are registered in Poliklinik Endokrin Metabolik RSUP Prof. Dr. R. D. Kandou Manado. The samples were processed in Prokita Laboratorium in Malalayang, Manado. Data analysis showed that there are significant difference between platelet aggregation value examined using ADP 5 µm agonist in diabetic patient with vascular complications and diabetic patients without vascular compications (p = 0.004). The same result were obtained from comparing the platelet agggregation value examined using ADP 10 µm agonist (p = 0.000). There are significant difference between platelet aggregation value in type 2 diabetes melitus patients with vascular complications and without complications. Keywords: Platelet aggregation, type 2 diabetes melitus, vascular complications.  Abstrak: : Diabetes Melitus menjadi masalah kesehatan di dunia. WHO memperkirakan ada 171 juta orang di dunia dengan diabetes pada tahun 2000 dan diproyeksikan meningkat menjadi 366 juta pada tahun 2030. Pada diabetes melitus terjadi disfungsi dari trombosit sehingga menyebabkan mikroangiopati, makrongiopati dan hiperaktivitas trombosit. Gangguan fungsi trombosit ini dihubungkan dengan berbagai komplikasi vaskuler. Penelitian ini menggunakan observasional analitik dengan menggunakan metode uji hipotesis komparatif. Subjek dalam penelitian ini berjumlah 30 orang, 15 orang pasien diabetes mellitus tipe 2 dengan komplikasi vaskular dan tanpa komplikasi vaskular yang terdaftar di Poliklinik Endokrin Metabolik RSUP Prof. Dr. R. D. Kandou Manado. Pembuatan sampel dilakukan di Laboratorium Prokita Malalayang Manado. Dari hasil analisis, didapatkan adanya perbedaan yang bermakna antara nilai agregasi trombosit yang diperiksa menggunakan agonis ADP 5 µm pada pasien dengan komplikasi vaskuler dan pasien diabetes tanpa komplikasi vaskuler (p = 0,004). Hasil yang sama juga didapatkan pada nilai agregasi trombosit yang diperiksa menggunakan agonis ADP 10 µm (p = 0,000). Kesimpulan dari penelitian ini didapatkan terdapat perbedaan signifikan antara nilai agregasi trombosit pada pasien diabetes mellitus tipe 2 dengan komplikasi vaskular dan tanpa komplikasi vaskular. Kata Kunci: Agregasi trombosit, diabetes melitus tipe 2, komplikasi vaskular.


2020 ◽  
Vol 319 (1) ◽  
pp. H133-H143 ◽  
Author(s):  
Haichen Lv ◽  
Ruopeng Tan ◽  
Jiawei Liao ◽  
Zhujing Hao ◽  
Xiaolei Yang ◽  
...  

Doxorubicin therapy in mice (antitumor dosage) markedly enhanced platelet functions measured as agonist-induced platelet aggregation, degranulation, and adhesion to endothelial cells, actions leading to thrombus formation and thrombosis-independent vascular injury. Clopidogrel treatment ameliorated thrombus formation and vascular toxicity induced by doxorubicin via inhibiting platelet activity.


1981 ◽  
Author(s):  
A I Woods ◽  
S S Meschengieser ◽  
N M Sutton ◽  
M A Lazzari

Abnormalities in platelet function tests have already been described in diabetic patients reflecting platelet hyperreactivity. An attempt to determine which of the tests seemed to be more affected in the diabetic population was done in a group of 34 diabetic patients (20 men and 14 women, age range 15-76). The tests performed included assay of Ristocetin Cofactor (McFarlane et al.) circulating platelet aggregates (CPA) (Wu-Hoak) and platelet aggregation induced by ADP in low concentration (0.6 x 10-6M) and Bovine Factor VIII (0.001 U/ml). In matched controls only 3.5% had a positive aggregation induced by Bovine F VIII and with ADP (0.6 x 10-6M% ) the extent of maximum aggregation was 30%.In 15 of the 34 patients (44%) aggregation induced by ADP in high dilution was greater than 50% and this was the test more frequently affected. The level of Ristocetin Cofactor was increased (>160%) in 12 of 34 patients (35%) and aggregation induced by BF VIII was positive also in 12 patients (35%). The detection of CPA was positive in 9 patients (26%). Two patients had spontaneous platelet aggregation and in them all the other tests performed were also positive. Three patients had 3 of the tests altered, and 11 patients only had 2 affected tests.The assay more affected was the ADP induced aggregation followed by the Ristocetin Cofactor levels and BF VIII induced aggregation. The test less affected was the CPA. A correlation with clinical data will be mentioned.


2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Tichapa Sirikarin ◽  
Titchaporn Palo ◽  
Sirikul Chotewuttakorn ◽  
Weerawadee Chandranipapongse ◽  
Suveerawan Limsuvan ◽  
...  

Background. Andrographis paniculata(AP) has been used in Thai traditional medicine to treat various infections, including the common cold and fever. Its bioactive compound, andrographolide, has shown antiplatelet activities in anin vitrostudy model. Since clinical studies of the effects of AP on the human platelet function have never been reported, we investigated its effect on platelet activity in ten healthy volunteers.Methods. Two grams of AP was taken 3 times within one day. The blood was withdrawn by venipuncture before and 2 and 24 hours after the AP administration to analyze the effects of AP on platelet aggregation, the expression of enzyme cyclooxygenase (COX) mRNA and protein, and TXB2, including P-selectin.Result. Even though there was no significant change in the studied parameters, this study exhibited patient-to-patient variability in platelet function. It was found that ADP-induced platelet aggregation tended to decrease after AP administration, while epinephrine-induced platelet aggregation in females tended to be higher than that in males for the entire study period. Moreover, COX-1 mRNA levels tended to decrease while P-selectin levels tended to rise after AP administration.Conclusion. These controversial results are possibly due to the multifactorial mechanisms of platelet aggregation as well as the multichemical composition of AP. Further study, probably at the molecular level, is needed to unveil the underlying mechanisms of action of AP.


2021 ◽  
pp. ASN.2020101440
Author(s):  
Constance C.F.M.J. Baaten ◽  
Marieke Sternkopf ◽  
Tobias Henning ◽  
Nikolaus Marx ◽  
Joachim Jankowski ◽  
...  

BackgroundPatients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings.MethodsTo help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function.ResultsWe included 73 studies in the systematic review to assess CKD’s overall effect on platelet function in patients; 11 of them described CKD’s effect on ex vivo platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ex vivo; ex vivo analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects.ConclusionsOverall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.


Blood ◽  
1977 ◽  
Vol 49 (2) ◽  
pp. 185-196 ◽  
Author(s):  
BB Weksler ◽  
M Gillick ◽  
J Pink

Abstract Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1–1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1513-1513
Author(s):  
Giordano Pula ◽  
Kai Schuh ◽  
Ulrich Walter ◽  
Keiichi I. Nakayama ◽  
Keiko Nakayama ◽  
...  

Abstract Filopodia are finger-like protrusions that play a crucial role in the guidance of cells through their extracellular and cellular environment. Blood platelets provide an essential early response system in haemostasis and arterial thrombosis and display a rapid and dramatic generation of filopodia upon activation, which play an essential role regulating their adhesive events leading to platelet aggregation. Here we report a novel and unexpected control mechanism for this explosive cellular rearrangement. Using pharmacological and genetic approaches we show that the novel isoform of protein kinase C, PKCδ, is a critical negative regulator of actin polymerization, filopodia formation and platelet aggregation. We show that PKCδ interacts with vasodilator-stimulated phosphoprotein (VASP), a major regulator of actin cytoskeleton dynamics, and regulates VASP phosphorylation. VASP is shown to be necessary for the PKCδ-dependent regulation of actin polymerization, filopodia formation and platelet aggregation. We therefore propose a causative link between the functional interaction of PKCδ with VASP and the role of the kinase as modulator of platelet activity.


Author(s):  
Antonio López Farré ◽  
Javier Modrego ◽  
José J. Zamorano-León

AbstractPlatelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.


1979 ◽  
Author(s):  
M. Zuzel ◽  
P.B.A. Kernoff ◽  
A.L. Willis ◽  
R.C. Paton ◽  
G.P. McNicol

DHLA causes a general inhibition of platelet reactions in standard in vitro tests of platelet function. Significantly more DHLA is required for the 50% inhibition (ID 50) of diabetic when compared to normal platelet reactions (Kernoff et al. Thrombosis & Haemostasis 38, 194, 1977). To investigate the cause of this difference we have studied kinetics of ADP-induced primary platelet aggregation, its inhibition by DHLA, and the formation of malondialdehyde (MDA) in the presence of DHLA in platelet-rich plasma of six healthy subjects and six diabetic patients with advanced microangiopathy. The results showed a significantly lower Km (ADP) for platelet aggregation in the diabetic group compared to normal. The (DHLA) of the competitive component of inhibition of platelet aggregation (prostaglandin production-mediated) was not significantly different In the two groups. Also, amounts of MDA formed in diabetic and normal PRP in the presence of DHLA were not significantly different. We conclude that the apparent low susceptibility of diabetic platelets to inhibition by DHLA might be a result of a primary hyper-reactivity of these platelets due to a cause other than an abnormality of the platelet PG production pathway.


2020 ◽  
Vol 21 (24) ◽  
pp. 9716
Author(s):  
Rana Bakhaidar ◽  
Sarah O’Neill ◽  
Zebunnissa Ramtoola

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0–2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.


Sign in / Sign up

Export Citation Format

Share Document