Trimetazidine Protective Effect Against Ischemia-Induced Susceptibility to Ventricular Fibrillation in Pigs

Vaillant, Fanny; Tsibiribi, Panayota; Bricca, Giampiero; Bui‐Xuan, Bernard; Bescond-Jacquet, Anne; Tabib, A.; Descotes, Jacques; Timour, Quadiri

doi:10.1007/s10557-007-6076-5

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…At the cellular level, TMZ preserves ATP production, reduces the generation of oxygen free radicals (Maupoil et al, 1990;Gambert et al, 2006;Kutala et al, 2006), and reduces intracellular acidosis and calcium overload (Kantor et al, 2000). TMZ has been shown to protect hearts from ischemia-induced electrical dysfunction leading to ventricular fibrillation (Vaillant et al, 2008), ischemia-reperfusion-induced damage to mitochondrial respiration (Guarnieri and Muscari, 1993), and ischemia-reperfusion injury by decreasing myocardial lactate content early at reperfusion (Pantos et al, 2005). Tritto et al (2005) demonstrated that TMZ attenuated tissue injury in postischemic hearts by inhibiting the activation of neutrophils.…”

Section: Preconditioning Of Mscs With Trimetazidine For Cell Therapy 547mentioning

confidence: 99%

Pharmacological Preconditioning of Mesenchymal Stem Cells with Trimetazidine (1-[2,3,4-Trimethoxybenzyl]piperazine) Protects Hypoxic Cells against Oxidative Stress and Enhances Recovery of Myocardial Function in Infarcted Heart through Bcl-2 Expression

Wisel¹,

Khan²,

Kuppusamy³

et al. 2009

J Pharmacol Exp Ther

122

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Stem cell transplantation is a possible therapeutic option to repair ischemic damage to the heart. However, it is faced with a number of challenges including the survival of the transplanted cells in the ischemic region. The present study was designed to use stem cells preconditioned with trimetazidine (1-[2,3,4-trimethoxybenzyl]piperazine; TMZ), a widely used anti-ischemic drug for treating angina in cardiac patients, to increase the rate of their survival after transplantation. Bone marrow-derived rat mesenchymal stem cells (MSCs) were subjected to a simulated host tissue environment by culturing them under hypoxia (2% O 2 ) and using hydrogen peroxide (H 2 O 2 ) to induce oxidative stress. MSCs were preconditioned with 10 M TMZ for 6 h followed by treatment with 100 M H 2 O 2 for 1 h and characterized for their cellular viability and metabolic activity. The preconditioned cells showed a significant protection against H 2 O 2 -induced loss of cellular viability, membrane damage, and oxygen metabolism accompanied by a significant increase in HIF-1␣, survivin, phosphorylated Akt (pAkt), and Bcl-2 protein levels and Bcl-2 gene expression. The therapeutic efficacy of the TMZ-preconditioned MSCs was evaluated in an in vivo rat model of myocardial infarction induced by permanent ligation of left anterior descending coronary artery. A significant increase in the recovery of myocardial function and up-regulation of pAkt and Bcl-2 levels were observed in hearts transplanted with TMZ-preconditioned cells. This study clearly demonstrated the potential benefits of pharmacological preconditioning of MSCs with TMZ for stem cell therapy for repairing myocardial ischemic damage.

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Section: Preconditioning Of Mscs With Trimetazidine For Cell Therapy 547mentioning

confidence: 99%

Pharmacological Preconditioning of Mesenchymal Stem Cells with Trimetazidine (1-[2,3,4-Trimethoxybenzyl]piperazine) Protects Hypoxic Cells against Oxidative Stress and Enhances Recovery of Myocardial Function in Infarcted Heart through Bcl-2 Expression

Wisel¹,

Khan²,

Kuppusamy³

et al. 2009

J Pharmacol Exp Ther

122

View full text Add to dashboard Cite

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“…It is also known that long‐term treatment with TMZ alleviates the myocardial accumulation of the oxidation reactive form and prevents lipid per‐oxidation . It improves the activity of the superoxide dismutase (an antioxidant enzyme) and relieves the oxidative stress phenomena . TMZ used in standard pharmacological therapy and in a domiciliary exercise programme improves a functional performance in patients with peripheral arterial diseases .…”

Section: Introductionmentioning

confidence: 99%

“…[10] It improves the activity of the superoxide dismutase (an antioxidant enzyme) and relieves the oxidative stress phenomena. [11,12] TMZ used in standard pharmacological therapy and in a domiciliary exercise programme improves a functional performance in patients with peripheral arterial diseases. [13,14] Although TMZ is mainly applied to prophylaxis and therapy of cardiovascular diseases, it is also used in the case of patients with ischemic heart diseases and stable angina or acute coronary syndromes.…”

Section: Introductionmentioning

confidence: 99%

The prevalence of trimetazidine use in athletes in Poland: excretion study after oral drug administration

Jarek

Wójtowicz

Kwiatkowska

et al. 2014

Drug Testing and Analysis

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Stimulants, together with anabolic androgenic steroids, are regarded as one of the most popular doping substances in sport. Owing to a great variety of these substances and new designer drugs being introduced to the market, each year the World Anti-Doping Agency (WADA) updates the list of substances and methods prohibited in sport. On 1 January 2014, a new doping agent - trimetazidine (TMZ) - was added to the WADA Prohibited List. TMZ, a substance prohibited in competition, is classified in the S6b Specified Stimulant Group. TMZ is used as a well-known cardiologic drug with confirmed biochemical and clinical activity. According to knowledge of the pharmacology and mechanism of TMZ action, TMZ can be used by athletes to improve physical efficiency, especially in the case of endurance sports. This study presents the phenomena of TMZ use by Polish athletes involved in anti-doping control in the WADA-accredited laboratory in Warsaw (Poland) between 2008 and 2013. Samples were taken from the athletes of such disciplines as cycling, athletics, and triathlon. Moreover, the elimination study of TMZ has been conducted to establish the change of TMZ concentration in urine sample after oral administration of a single or double (during the long-term therapy) dose. TMZ was monitored in urine samples by gas chromatography-mass spectrometry-nitrogen phosphorus detection (GC-MS-NPD).

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“…TMZ: HS and resuscitation, TMZ at a 10 mg/kg dose. 16 HTK: HS and resuscitation, HTK administered intravenously at a constant rate. 17 ALO: HS and resuscitation, ALO at a 50 mg/kg dose.…”

Section: Study Groupsmentioning

confidence: 99%

Bretschneider Solution and Two Antianginal Drugs Protect Peripheral Tissue in an Animal Model of Hemorrhagic Shock

Fragola

Cao

Tumarkin

et al. 2022

Journal of Cardiovascular Pharmacology

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:Shock and subsequent resuscitation provoke ischemia-reperfusion injury. Trimetazidine (TMZ), allopurinol (ALO), and histidine–tryptophan–ketoglutarate (HTK) solution, can protect from ischemia-reperfusion injury in chronic coronary syndromes and in transplantation. The objective of the current study is to compare, in a hemorrhagic shock and standard resuscitation animal model, organ damage parameters between placebo and treatment with TMZ, ALO, or HTK. Shock was induced in Wistar rats by controlled arterial bleeding, maintaining mean arterial pressure between 38 and 42 mm Hg for 60 minutes; then, drawn blood was reinfused. Animals were divided into: Sham (n = 4), Control (n = 6), TMZ (n = 7), ALO (n = 9), and HTK (n = 7). At the end of the experiment, animals were sacrificed and tissue harvested. TMZ, ALO and HTK decreased histopathologic damage in heart [Control: 1.72 (1.7–1.77); TMZ: 1.75 (1.72–1.79); ALO: 1.75 (1.74–1.8); HTK: 1.82 (1.78–1.85); all P < 0.05], kidney [Control: 3 (2–3); TMZ: 1 (1–2); ALO: 1 (1-1); HTK: 1(1-1); all P < 0.05] and intestine [Control: 3 (2–3); TMZ: 1 (1–2); ALO: 1 (1-1); HTK: 1 (0–2); all P < 0.05]. Also, treatment with TMZ, ALO, and HTK increased immunohistochemical expression of thioredoxin-1 in heart [Control: 6.6 (5.6–7.4); TMZ: 9.5 (8.1–9.7); ALO: 9.1 (8.4–10.2); HTK: 14.2 (12.6–15); all P < 0.05]; and kidney [Control: 4.6 (4–5.1); TMZ: 9.7 (9.3–9.9); ALO: 9.6 (9–9.9); HTK: 16.7 (16.1–17); all P < 0.05]. In an experimental model of hemorrhagic shock, TMZ, ALO, and HTK solution attenuated cell damage in multiple parenchyma and increased antioxidant defenses.

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Trimetazidine Protective Effect Against Ischemia-Induced Susceptibility to Ventricular Fibrillation in Pigs

Abstract: TMZ limited ischemia-induced electrical dysfunction leading to cardiac susceptibility to VF by decreasing lipid peroxidation and maintaining ionic homeostasis. TMZ could therefore provide protection against ischemia-induced VF.

Cited by 10 publications

References 46 publications

Pharmacological Preconditioning of Mesenchymal Stem Cells with Trimetazidine (1-[2,3,4-Trimethoxybenzyl]piperazine) Protects Hypoxic Cells against Oxidative Stress and Enhances Recovery of Myocardial Function in Infarcted Heart through Bcl-2 Expression

Pharmacological Preconditioning of Mesenchymal Stem Cells with Trimetazidine (1-[2,3,4-Trimethoxybenzyl]piperazine) Protects Hypoxic Cells against Oxidative Stress and Enhances Recovery of Myocardial Function in Infarcted Heart through Bcl-2 Expression

The prevalence of trimetazidine use in athletes in Poland: excretion study after oral drug administration

Bretschneider Solution and Two Antianginal Drugs Protect Peripheral Tissue in an Animal Model of Hemorrhagic Shock

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