l-carnitine modulates blood platelet oxidative stress

Saluk-Juszczak, Joanna; Olas, Beata; Wachowicz, Barbara; Głowacki, Rafał; Bald, Edward

doi:10.1007/s10565-009-9148-4

Cited by 28 publications

(17 citation statements)

References 58 publications

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“…17 The excessive production of NO from iNOS can react rapidly with superoxide anion to cause the formation of the highly reactive peroxynitrite (ONOO−), which is involved in the oxidation and nitration of fibrinogen (a key protein in the coagulation cascade) and plasminogen (the main protein of fibrinolysis process). 18 In agreement with this, mutant mice lacking iNOS were resistant to LPSinduced mortality. 19 In contrast, the blockade of all isoforms of NOS with L-NAME did not protect from the lethal septic shock, suggesting that eNOS may counteract the negative effect of iNOS.…”

Section: Discussionsupporting

confidence: 59%

A primary role for kinin B1 receptor in inflammation, organ damage, and lethal thrombosis in a rat model of septic shock in diabetes

et al. 2015

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Diabetes mellitus and septic shock increase the incidence of mortality by thrombosis. Although kinin B1 receptor (B1R) is involved in both pathologies, its role in platelet function and thrombosis remains unknown. This study investigates the expression, the inflammatory, and pro-thrombotic effects of B1R in a model of septic shock in diabetic rats. SpragueDawley rats were made diabetic with streptozotocin (STZ) (65 mg/kg, i.p.). Four days later, control and STZ-diabetic rats were injected with lipopolysaccharide (LPS) (2 mg/kg, i.p.) or the vehicle. B1R antagonist (SSR240612, 10 mg/kg by gavage) was given either acutely (12 and 24 h prior to endpoint analysis) or daily for up to 7 days. Moreover, a 7-day treatment was given either with cyclooxygenase (COX)-2 inhibitor (niflumic acid, 5 mg/kg, i.p.), non-selective COX-1 and COX-2 inhibitor (indomethacin, 10 mg/kg, i.p.), non-selective nitric oxide synthase (NOS) inhibitor (L-NAME, 50 mg/kg by gavage), iNOS inhibitor (1400W, 5 mg/kg, i.p.), or heparin (100 IU/kg, s.c.). The following endpoints were measured: edema and vascular permeability (Evans blue dye), B1R expression (qRT-PCR, western blot, flow cytometry), aggregation in platelet-rich plasma (optical aggregometry), and organ damage (histology). Rats treated with STZ, LPS, and STZ plus LPS showed significant increases in edema and vascular permeability (heart, kidney, lung, and liver) and increased expression of B1R in heart and kidney (mRNA) and platelets (protein). Lethal septic shock induced by LPS was enhanced in STZ-diabetic rats and was associated with lung and kidney damage, including platelet micro-aggregate formation. SSR240612 prevented all these abnormalities as well as STZ-induced hyperglycemia and LPS-induced hyperthermia. Similarly to SSR240612, blockade of iNOS and COX-2 improved survival. Data provide the first evidence that kinin B1R plays a primary role in lethal thrombosis in a rat model of septic shock in diabetes. Pharmacological rescue was made possible with B1R antagonism or by inhibition of iNOS and COX-2, which may act as downstream mechanisms.

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Section: Discussionsupporting

confidence: 59%

A primary role for kinin B1 receptor in inflammation, organ damage, and lethal thrombosis in a rat model of septic shock in diabetes

et al. 2015

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“…Following treatment with ONOO - , NT expression was raised in CHD patients, but not in healthy donors. Recent data has demonstrated that some supplements such as L-carnitine can protect platelets against the nitrating effects of ONOO - [43] and it is possible that platelet levels of endogenous antioxidants were higher in healthy donors. Similarly, the O 2 -• generating X/XO system or XO alone, which would likely generate O 2 -• anions, also caused a small increase in platelet NT expression in CHD patients, likely through an interaction with platelet-derived • NO.…”

Section: Discussionmentioning

confidence: 99%

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

Watt

Ewart

Greig

et al. 2012

Thrombosis Research

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BackgroundThe effect of reactive oxygen species (ROS) on platelet function in coronary heart disease (CHD) is complex and poorly defined. Platelet aggregation studies in healthy volunteers have demonstrated contrasting results when platelets are exposed to ROS. We investigated the effect of ROS on whole blood aggregation (WBA) and the endothelial cell-platelet interaction in patients with CHD.Methods and ResultsROS generated by xanthine and xanthine oxidase caused a concentration-dependent inhibition of WBA in blood from healthy donors and patients with CHD. In patients with CHD, 100 μM xanthine and 100 mU/ml xanthine oxidase inhibited WBA in response to 3 μg/ml collagen by 28.9% (95% CI 15.9%-41.8%, p < 0.001) and in response to 5 μM ADP by 36.0% (95% CI 9.6%-62.4%, p = 0.005). Using nitrotyrosine expression, platelets isolated from patients with CHD were found to be susceptible to peroxynitrite damage. The addition of 1 × 105 cultured endothelial cells inhibited WBA in response to 3 μg/ml collagen by 31.2% (95% CI 12.2%-50.2%, p < 0.05) and in response to 5 μM ADP by 31.6% (95% CI 2.5-60.7%, p < 0.05). Addition of xanthine and xanthine oxidase did not alter this effect, however pre-treatment of endothelial cells with a nitric oxide synthase inhibitor (L-NAME) partly reversed the inhibition.ConclusionROS inhibit WBA in blood from patients with CHD. Whilst endothelial cells also inhibit WBA, the effect is attenuated by L-NAME, suggesting that nitric oxide is likely to remain an important protective mechanism against thrombosis in CHD.

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“…Recently, Lcarnitine has been proposed as a potential adjuvant treatment to improve anaemia, thrombocytopenia, leukopenia and immunological function. [68][69][70][71][72][73] In a recent study, L-carnitine added to Peg-IFN-α plus ribavirin led to less decrease of platelet count during antiviral therapy. 74 Some studies indicate that L-carnitine modulates platelet functions and production through antioxidant mechanisms and the inhibition of the arachidonic acid cascade.…”

Section: L-carnitinementioning

confidence: 99%

Chronic hepatitis C-associated thrombocytopenia: aetiology and management

Fouad

2013

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Thrombocytopenia is perhaps the most common haematological abnormality in patients with chronic hepatitis C virus (HCV) infection. In these patients, the presence of thrombocytopenia may be a limiting factor when considering antiviral therapy and may be associated with decreased sustained virological response rates. Thrombocytopenia may interfere with diagnostic procedures such as liver biopsy, because of risk of bleeding.Pathogenetic mechanisms include hypersplenism secondary to portal hypertension, bone marrow suppression resulting from either HCV itself or interferon treatment, and aberrations of the immune system resulting in the formation of anti-platelet antibodies and/or immunecomplexes that bind to platelets and facilitate their premature clearance. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease. Therapeutic options include pharmacological and non-pharmacological therapies. This review summarizes the available data on these therapeutic options. KEYWORDS: thrombocytopenia, hepatitis C virus (HCV), cytokines Definition and prevalenceThrombocytopenia has been defined as a platelet count <150,000 cells/µL. In a recent systematic review, the definitions of thrombocytopenia varied between studies and were based either on platelet counts, with threshold levels ranging between <100,000 cells/µL and <180,000 cells/µL or on criteria set in haematological guidelines. The prevalence of thrombocytopenia related to chronic liver disease has been reported as 15% to 70% in patients with advanced fibrosis and portal hypertension, depending on the stage of the disease and the platelet level used to define thrombocytopenia. In patients with chronic HCV infection, the prevalence of thrombocytopenia ranged from 0.16% to 45.4% and more than half of the studies reported a prevalence of 24% or more. 1 Aetiology of thrombocytopenia in patients with chronic HCVThe pathophysiology of thrombocytopenia in patients with HCV-related chronic liver disease is complex and involves the interaction of multiple factors. In general, these factors may be

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l-carnitine modulates blood platelet oxidative stress

Cited by 28 publications

References 58 publications

A primary role for kinin B1 receptor in inflammation, organ damage, and lethal thrombosis in a rat model of septic shock in diabetes

A primary role for kinin B1 receptor in inflammation, organ damage, and lethal thrombosis in a rat model of septic shock in diabetes

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease

Chronic hepatitis C-associated thrombocytopenia: aetiology and management

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