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1.
J Assoc Physicians India ; 69(4): 11-12, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34470192

RESUMO

The results of the ATPCI (efficAcy and safety of Trimetazidine in patients with angina pectoris treated by Percutaneous Coronary Intervention) study showed no significant difference in the incidence of primary endpoint events between trimetazidine and the placebo group in angina patients who recently underwent percutaneous coronary intervention. The study had limitations specific to the design and selection of the target patient population. However, safety outcomes for trimetazidine were reconfirmed in this study. In this article, we discuss the limitations of study design, patient inclusion criteria and their implications in routine practice. We have also dissected the evidence to tweeze out patient groups who are likely to benefit from trimetazidine treatment.


Assuntos
Intervenção Coronária Percutânea , Trimetazidina , Angina Pectoris/tratamento farmacológico , Humanos , Projetos de Pesquisa , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico
2.
Arq Bras Cardiol ; 117(2): 290-297, 2021 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34495221

RESUMO

BACKGROUND: Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses. OBJECTIVES: The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury. METHODS: Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey's post hoc test. A p-value <0.05 was considered significant. RESULTS: NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury. CONCLUSIONS: The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.


Assuntos
Traumatismo por Reperfusão , Trimetazidina , Animais , Barorreflexo , Flavanonas , Rim , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Núcleo Solitário , Trimetazidina/farmacologia
4.
Am J Ther ; 28(5): e540-e547, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34321406

RESUMO

BACKGROUND: In coronary artery disease (CAD), reduction of perfusion in coronary arteries is followed by increases of oxidative stress and decreases of adenosine triphosphate reserve. In this condition, trimetazidine (TMZ), a metabolic anti-ischemic agent, seems to be an ideal therapeutic agent because it increases mitochondrial adenosine triphosphate production. STUDY QUESTION: To evaluate the impact of TMZ on oxidative stress, inflammation, endothelial dysfunction, and long-term prognosis in CAD. STUDY DESIGN: Patients with CAD with symptoms not adequately controlled were enrolled consecutively for a period of 18 months. MEASURES AND OUTCOMES: Five hundred seventy patients with CAD were enrolled in a prospective study and divided into 4 groups in relation with the type of CAD and the addition of TMZ to optimal medical therapy (OMT). The impact of TMZ added to OMT on oxidative stress (total antioxidant status, antioxidized low-density lipoprotein antibodies, and antimyeloperoxidase antibodies), endothelial dysfunction (flow-mediated dilatation and von Willebrand factor activity), and inflammation (C-reactive protein and fibrinogen) at 6 months and on long-term prognosis in CAD in comparison with OMT at 5 years of follow-up was evaluated. RESULTS: At 6 months, TMZ added to OMT significantly decreased the incidence of oxidative stress in CAD (P < 0.03) and reduced endothelial dysfunction and inflammation only in non-ST-elevation acute coronary syndrome (NSTE-ACS, P < 0.04). TMZ added to OMT with or without interventional/surgical vascularization led to decreased readmission for NSTE-ACS and heart failure (P < 0.05) in all patients with CAD and a significantly reduced incidence of cardiovascular death, acute myocardial infarction, and stroke (P < 0.05) in patients with NSTE-ACS at 5 years of follow-up. CONCLUSIONS: In patients with NSTE-ACS, TMZ added to OMT with or without interventional and/or surgical reperfusion reduced oxidative stress, endothelial dysfunction, inflammation, and major acute cardiovascular events, whereas in patients with chronic coronary syndrome, TMZ decreased oxidative stress and readmission for ACS and heart failure.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Trimetazidina , Doença da Artéria Coronariana/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Estresse Oxidativo , Prognóstico , Estudos Prospectivos , Trimetazidina/uso terapêutico
5.
Orv Hetil ; 162(29): 1167-1171, 2021 07 18.
Artigo em Húngaro | MEDLINE | ID: mdl-34274921

RESUMO

Összefoglaló. Bevezetés: A közelmúltban publikált ATPCI-vizsgálat azt eredményezte, hogy közvetlenül a sikeres revaszkularizáció után alkalmazott trimetazidin biztonságos volt, de nem volt effektívebb a cardiovascularis halál, anginarekurrencia, cardialis hospitalizáció tekintetében, mint a random kettos vakmódszerrel alkalmazott placebo. Célkituzés: Az általunk korábban végzett ONECAPS nyitott, obszervációs vizsgálat retrospektív analízisét kívántuk elvégezni annak eldöntésére, hogy az anginás betegeknél van-e különbség a trimetazidin prolong hatásosságában annak megfeleloen, hogy korábban revaszkularizáció történt. Módszer: 1670, anginás betegbol 1008 nem volt revaszkularizálva, míg 662 korábban revaszkularizáción esett át. Az életkorban, társbetegségben nem volt különbség a két csoport között. A betegeknél a heti anginaszámnak és a nitroglicerin-fogyasztásnak, illetve az angina súlyosságának a változását vizsgáltuk a trimetazidin prolong 80 mg napi egyszeri alkalmazása során a revaszkularizált és a nem revaszkularizált betegcsoportban. Eredmények: Mind a revaszkularizált, mind a nem revaszkularizált betegcsoportban szignifikáns csökkenést (p<0,0001) eredményezett a trimetazidin mind a heti anginaszámban, mind a rövid hatású nitroglicerin fogyasztásában. Emellett mindkét betegcsoportban növekedett a Kanadai Cardiovascularis Társaság (CCS) osztályozása szerinti I. súlyosságú angina aránya, és csökkent a CCS III., illetve CCS IV . aránya is. Mindezt a hatást úgy érték el, hogy a revaszkularizált betegeknél 90% felett volt a sztatin, az ACEI/ARB, illetve a béta-blokkoló használata. Következtetés: A trimetazidin prolong napi egyszeri 80 mg adása szignifikánsan csökkenti a heti anginaszámot, nitroglicerin-fogyasztást, illetve az angina súlyosságát. Ezen hatása független attól, hogy a beteg korábban részesült-e revaszkularizációban vagy sem. Orv Hetil. 2021; 162(29): 1167-1171. INTRODUCTION: The recently published ATPCI study resulted in the safety of trimetazidine administered immediately after successful revascularization but was not more effective (cardiovascularis death, recurrence of angina, hospitalization for cardiac event) than the randomized double-blind placebo. OBJECTIVE: A retrospective analysis of our previously published ONECAPS open-label observational study was performed to determine whether there was a difference in the efficacy of trimetazidin prolong in the angina patients according to whether or not they had previously undergone revascularization. METHOD: Of the 1670 angina patients, 1008 were not revascularized, while 662 had previously undergone revascularization. There was no difference in age or comorbidity between the two groups. Patients were examined for changes in weekly angina, short-acting nitroglycerin use and angina severity during once-daily administration of trimetazidine prolong 80 mg in revascularized and non-revascularized study groups. RESULTS: In both the revascularized and non-revascularized group, trimetazidine resulted in a significant reduction (p<0.0001) in both weekly angina count and short-acting nitroglycerin use. In addition, the proportion of angina with Canadian Cardiovascular Society (CCS) I increased and the proportion of CCS III and CCS IV decreased in both patient groups as well. All of this effect was achieved with statin, ACEI/ARB, and beta-blocker use above 90% in revascularized patients. CONCLUSION: Trimetazidine prolong 80 mg once daily significantly reduced the number of angina per week, the use of short-acting nitroglycerin per week, and the severity of angina. This effect is independent of whether the patient has previously received revascularization. Orv Hetil. 2021; 162(29): 1167-1171.


Assuntos
Angina Estável , Trimetazidina , Angina Estável/tratamento farmacológico , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Canadá , Humanos , Estudos Retrospectivos
6.
Luminescence ; 36(6): 1435-1443, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33982840

RESUMO

Water-soluble and highly stable N,S-doped CQDs (N,S-CQDs) were synthesized using a low-cost strategy with citric acid and thiosemicarbazide in one step for use as a fluorescent nanosensor. The achieved N,S-CQDs produced strong emission at 446 nm upon excitation at 370 nm and a high quantum yield of 58.5%. The quenching effect on the prepared N,S-CQDs was utilized for determination of trimetazidine (TMZ) spectrofluorimetrically over a wide linear range 0.04-0.5 µM (0.0106-0.133 µg ml-1 ) and a low limit of detection of 0.01 µM (0.002 µg ml-1 ). Furthermore, CDs were used as a simple and rapid fluorescent probe to determine TMZ in its pharmaceutical formulations as well as in human plasma. The method was tested in compliance with International Council for Harmonisation guidelines. The results obtained were compared statistically with those given for a reported method showing no significant variation regards accuracy and precision.


Assuntos
Pontos Quânticos , Trimetazidina , Carbono , Humanos , Nitrogênio , Enxofre
7.
Biochem Pharmacol ; 190: 114634, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34058186

RESUMO

BACKGROUND: Inflammation is a key process during atherosclerotic lesion development and propagation. Recent evidence showed clearly that especially the inhibition of interleukin (IL)-1ß reduced atherosclerotic adverse events in human patients. Fatty acid oxidation (FAO) was previously demonstrated to interact with the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) pathway which is required for mature IL-1ß secretion. To understand possible anti-inflammatory properties of FAO inhibition, we tested the effect of pharmacological FAO inhibition using the inhibitor for long-chain 3-ketoacyl coenzyme A thiolase trimetazidine on atherosclerotic plaque development and inflammation. EXPERIMENTAL APPROACH: The effect of FAO inhibition was determined in LDL-R-/- male mice on a C57/BL6 background. In vitro effects of trimetazidine treatment were analyzed in human umbilical vein endothelial cells and human monocyte derived macrophages. KEY RESULTS: We were able to demonstrate that inhibition of FAO reduced atherosclerotic plaque growth. We did not find direct anti-inflammatory properties of trimetazidine in endothelial cells or macrophages in vitro. However, we found that the activation of the NLRP3 system and the secretion of IL-1ß were significantly reduced in macrophages after FAO inhibition. These results were confirmed in atherosclerotic lesions of mice treated with trimetazidine as they showed a significant reduction of IL-1ß and cleaved caspase-1 in the atherosclerotic lesion as well as of IL-1ß and IL-18 in the circulation. CONCLUSION: Overall, we therefore suggest that the main mechanism of reducing inflammation of trimetazidine and FAO inhibition is the reduction of the NLRP-3 activation leading to reduced levels of the proinflammatory cytokine IL-1ß.


Assuntos
Aterosclerose/prevenção & controle , Ácidos Graxos/metabolismo , Macrófagos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores de LDL/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Metabolismo dos Lipídeos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Oxirredução , Receptores de LDL/genética , Trimetazidina/farmacologia , Vasodilatadores/farmacologia
8.
Pharmacology ; 106(5-6): 332-340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33849026

RESUMO

INTRODUCTION: The presence of mercury in the environment is a worldwide concern. Inorganic mercury is present in industrial materials, is employed in medical devices, is widely used in batteries, is a component of fluorescent light bulbs, and it has been associated with human poisoning in gold mining areas. The nephrotoxicity induced by inorganic mercury is a relevant health problem mainly in developing countries. The primary mechanism of mercury toxicity is oxidative stress. Trimetazidine (TMZ) is an anti-ischemic drug, which inhibits cellular oxidative stress, eliminates oxygen-free radicals, and improves lipid metabolism. The aim of this study was to evaluate whether the administration of TMZ protects against mercuric chloride (HgCl2) kidney damage. METHODS: Adult male Wistar rats received only HgCl2 (4 mg/kg bw, sc) (Hg group, n = 5) or TMZ (3 mg/kg bw, ip) 30 min before HgCl2 administration (4 mg/kg bw, sc) (TMZHg group, n = 7). Simultaneously, a control group of rats (n = 4) was studied. After 4 days of HgCl2 injection, urinary flow, urea and creatinine (Cr) plasma levels, Cr clearance, urinary glucose, and sodium-dicarboxylate cotransporter 1 (NaDC1) in urine were determined. Lipid peroxidation (MDA) and glutathione (GSH) levels were measured in kidney homogenates. RESULTS: Rats only treated with HgCl2 showed an increase in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, and NaDC1 urinary excretion as compared with the control group and a decrease in Cr clearance. TMZHg group showed a decrease in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, NaDC1 urinary excretion, and an increase in Cr clearance when compared to the Hg group. Moreover, MDA and GSH levels observed in Hg groups were decreased and increased, respectively, by TMZ pretreatment. CONCLUSION: TMZ exerted a renoprotective action against HgCl2-induced renal injury, which might be mediated by the reduction of oxidative stress. Considering the absence of toxicity of TMZ, its clinical application against oxidative damage due to HgCl2-induced renal injury should be considered. The fact that TMZ is commercially available should simplify and accelerate the translation of the present data "from bench to bedside." In this context, TMZ become an interesting new example of drug repurposing.


Assuntos
Nefropatias/prevenção & controle , Intoxicação por Mercúrio/prevenção & controle , Substâncias Protetoras/farmacologia , Trimetazidina/farmacologia , Animais , Creatinina/sangue , Transportadores de Ácidos Dicarboxílicos/urina , Glutationa/metabolismo , Glicosúria/induzido quimicamente , Glicosúria/prevenção & controle , Nefropatias/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Cloreto de Mercúrio/efeitos adversos , Transportadores de Ânions Orgânicos Dependentes de Sódio/urina , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Cloreto de Sódio/urina , Simportadores/urina , Trimetazidina/uso terapêutico , Ureia/sangue , Micção/efeitos dos fármacos
9.
eNeuro ; 8(3)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33863783

RESUMO

Trimetazidine (TMZ), an antianginal drug, can worsen the symptoms of movement disorders, therefore, the European Medicines Agency (EMA) recommended avoiding the use of this drug in Parkinson's disease (PD). We investigated the impact of this recommendation on the observed trend of TMZ use in PD in Hungary from 2010 to 2016 by conducting a nationwide, retrospective study of health administrative data of human subjects. Interrupted time series analyses were performed to explore changes in user trends after the EMA recommendations. We found that TMZ use in PD decreased by 6.56% in each six-month interval after the EMA intervention [a change in trend of -530.22, 95% confidence interval (CI) = -645.00 to -415.44, p < 0.001 and a decrease in level of -567.26, 95% CI = -910.99 to -223.53, p = 0.005 12 months postintervention]. TMZ discontinuation was the highest immediately after the intervention, however, its rate slowed down subsequently (a change in trend of -49.69, 95% CI = -85.14 to -14.24, p = 0.11 without significant level effects). The rate of new TMZ prescriptions did not reduce significantly, therefore, the decreased overall use was mainly attributable to the increased rate of discontinuation only. The main indications for TMZ use were circulatory system disorders, especially angina pectoris, however, off-label utilization was also considerable (40%). The EMA recommendations on TMZ use seem to be only moderately effective in Hungary. Although the number of patients with PD on the drug modestly decreased after the EMA restrictions, TMZ is still widely used in PD for both on-label and off-label indications.


Assuntos
Doença de Parkinson , Trimetazidina , Angina Pectoris/tratamento farmacológico , Humanos , Doença de Parkinson/tratamento farmacológico , Estudos Retrospectivos , Trimetazidina/uso terapêutico , Vasodilatadores
10.
Expert Rev Cardiovasc Ther ; 19(5): 457-464, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33823738

RESUMO

Background:Ranolazine and trimetazidine are piperazine derivatives used in antianginal therapy. There are data on the use of these drugs in the treatment of neuropathic pain. In this study, it was aimed to evaluate the antinociceptive effects of ranolazine and trimetazidine.Methods: Sixty patients who were started on trimetazidine or ranolazine treatment were included in the study. The patients were evaluated with Seattle Angina Questionnaire (SAQ), Visual Analog Scale (VAS) and State-Trait Anxiety Inventory (STAI) on the first day of treatment and at the first month follow-up.Results: The SAQ scores of the patients given ranolazine were statistically significantly higher than the patients given trimetazidine. The most significant increase was observed in terms of treatment satisfaction (53.03 ± 8.11 vs. 72.88 ± 5.29, p < 0.001) and quality of life (49.79 ± 8.62 vs. 68.01 ± 0.65, p = 0.016). The decrease in VAS (p = 0.001) and the decrease in STAI scores (p = 0.002) after treatment in the ranolazine group were significantly higher than in the trimetazidine group.Conclusions: Ranolazine and trimetazidine are two effective drugs in antianginal treatment. While both drugs are effective on general systemic musculoskeletal pain and anxiety, the efficacy of ranolazine is more pronounced.


Assuntos
Analgésicos/uso terapêutico , Ranolazina/uso terapêutico , Trimetazidina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Vasodilatadores/uso terapêutico
11.
Bull Exp Biol Med ; 170(6): 763-768, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33893960

RESUMO

The anxiolytic and analgesic properties of compound ALM-802, a cardiotropic linear methoxyphenyltriazaalkane derivative, combining pharmacophore elements of p-FOX inhibitors trimetazidine and ranolazine were studied in vivo. In the elevated plus-maze test, ALM-802 after acute intraperitoneal administration in doses of 1-8 mg/kg dose-dependently prevented the development of anxiety in BALB/c mice. Chronic intraperitoneal administration of ALM-802 in a dose of 2 mg/kg to alcohol-preferring rats attenuated anxiogenesis induced by ethanol withdrawal. ALM-802 demonstrated antinociceptive activity in C57BL/6 mice during thermal stimulation of nociceptors in the hot plate test and during modeling of visceral pain in the acetic acid writhing test. Thus, ALM-802 exhibits anxiolytic and analgesic properties in the dose range corresponding to its anti-ischemic and antiarrhythmic effects.


Assuntos
Nociceptividade/efeitos dos fármacos , Trimetazidina/uso terapêutico , Animais , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nociceptores/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo
12.
Medicine (Baltimore) ; 100(15): e25491, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847660

RESUMO

BACKGROUND: To the best of our knowledge, there is no study that has conducted a review investigating the clinical efficacy and safety of bisoprolol combined with trimetazidine on chronic heart failure (CHF) patients with chronic obstructive pulmonary disease (COPD). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of bisoprolol combined with trimetazidine on CHF patients with COPD. METHODS: Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library will be searched in April 2021 by 2 independent reviewers. For search on PubMed, the following search terms will be used: "trimetazidine, bisoprolol, chronic heart failure, chronic obstructive pulmonary disease." In order to achieve a consistency of extracted items, the data extractors will extract data from a sample of eligible studies. The outcomes include all-cause mortality and hospitalization for cardiac or/and respiratory causes; left ventricular structure and function; and functional scores. Review Manager software (v 5.4; Cochrane Collaboration) will be used for the meta-analysis. Two independent reviewers will assess the risk of bias of the included studies at study level. Any disagreements will be discussed and resolved in discussion with a third reviewer. RESULTS: The results of our review will be reported strictly following the PRISMA criteria. CONCLUSIONS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/ZWPRB.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Bisoprolol/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Trimetazidina/administração & dosagem , Vasodilatadores/administração & dosagem , Doença Crônica , Quimioterapia Combinada , Insuficiência Cardíaca/complicações , Humanos , Metanálise como Assunto , Estudos Observacionais como Assunto , Doença Pulmonar Obstrutiva Crônica/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
13.
Indian Heart J ; 73(1): 135-137, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33714401

RESUMO

RESULTS: of the efficAcy and safety of Trimetazidine in patients with angina pectoris having been treated by Percutaneous Coronary Intervention (ATPCI) study showed no significant difference in the incidence of primary endpoint events between trimetazidine and placebo group in angina patients who recently underwent percutaneous coronary intervention. However, the study had limitations specific to both, design and selection of patient population. Here, we present some explanations for the null effects of trimetazidine in the ATPCI study and their relevance in routine clinical practice.


Assuntos
Angina Pectoris/terapia , Intervenção Coronária Percutânea/métodos , Trimetazidina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Vasodilatadores/farmacologia
14.
Int J Med Sci ; 18(7): 1680-1686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746584

RESUMO

Background: Anti-stress capacity is important to resist the occurrence of adverse events. To observe the effects of exercise, trimetazidine alone or combined on the anti-stress capacity of mice, and further explore its potential mechanism. Methods: Forty-four C57BL/6 male mice aged 8 weeks were randomly divided into four groups (n=11 for each group): control group (group C), exercise group (group E), trimetazidine group (group T), exercise combined with trimetazidine group (group TE). After the intervention, each group was randomly subdivided into the exhaustive exercise (EE, n=6) and the non-EE (n=5) subgroups. The mice in the EE-subgroup underwent EE. Mice were sacrificed 12 hours later after EE. The myocardial ultrastructure and autophagosomes were observed under an electron microscope. The expression of autophagy-related proteins: BNIP3, LC3-II, and P62 were analyzed and the heat shock protein 70 mRNA transcription and protein expression were also investigated. Results: Exercise or trimetazidine increased the expression of BNIP3, LC3-II, and heat shock protein 70, decreased the expression of P62 pre- and post-EE while the combination has the synergistic effect. Conclusion: Exercise and trimetazidine, alone or combined enhanced the anti-stress capacity of mice significantly. The underlying mechanism may be associated with the promotion of autography and the expression of heat shock protein 70.


Assuntos
Doenças Cardiovasculares/terapia , Estresse Fisiológico , Trimetazidina/administração & dosagem , Adaptação Fisiológica/efeitos dos fármacos , Animais , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP70/metabolismo , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Masculino , Camundongos , Microscopia Eletrônica , Miocárdio/metabolismo , Miocárdio/patologia , Miocárdio/ultraestrutura , Condicionamento Físico Animal/fisiologia
15.
Environ Toxicol ; 36(6): 1217-1225, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33704910

RESUMO

Few studies have reported a prophylactic effect of the anti-ischemic trimetazidine (TRI) against cardiac toxicity caused by adriamycin (ADR). However, the mechanism of action of TRI remained incomplete. The cardioprotective mechanism(s) of TRI against ADR-induced cardiotoxicity was investigated in this study. Cardiotoxicity was induced in three groups of Wistar rats by injecting a single dose of ADR (10 mg/kg, i.p.). TRI was administered in two doses regimen, low (L) (2.5 mg/kg, i.p.) and high (H) (10 mg/kg, i.p.). The results of the study showed that both TRI L and H doses improved cardiac enzymes and pathology, while only the TRI H dose improved the electrocardiogram. Both TRI L and H doses decreased malondialdehyde and increased reduced glutathione and superoxide dismutase. Only TRI H dose increased glutathione peroxidase and catalase. Both TRI L and H doses decreased interleukin-1 beta and tumor necrosis factor-alpha (TNF-α). Both TRI L and H doses downregulated TNF-α, BAX, and vascular endothelial growth factor cardiac protein expression. The data obtained in this study provided evidence that TRI opposed ADR-induced cardiotoxicity. The mechanism could be due to improved antioxidant levels as well as inhibition of inflammation and programmed cell death.


Assuntos
Cardiomiopatias , Trimetazidina , Animais , Antioxidantes , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Doxorrubicina/toxicidade , Estresse Oxidativo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2/genética
16.
Medicine (Baltimore) ; 100(10): e24603, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725824

RESUMO

OBJECTIVES: This systematic review and meta-analysis assesses the utility of trimetazidine (TMZ) to prevent contrast induced nephropathy (CIN) in patients with renal insufficiency undergoing coronary angiography and angioplasty. MATERIALS AND METHODS: This meta-analysis was formulated and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of databases was conducted by 2 researchers independently for clinical trials, comparing hydration plus TMZ vs conventional hydration alone for prevention of CIN through January 2020. All patients had renal insufficiency (defined as GFR < 89 ml/minute/1.73 m2) and the outcome of interest was the incidence of contrast induced acute kidney injury. The odds ratio (OR) was estimated with 95% confidence interval (CI). Heterogeneity was reported with the I2 statistic, using a fixed-effects model, and >50% of I2 was considered to be statistically significant. RESULTS: Eleven studies, 1611 patients, met the inclusion/exclusion criteria: 797 patients comprised the TMZ plus hydration group and the remaining 814 patients comprised the control (hydration only) group. Heterogeneity was low I2 = 0%, P = .84, and the heterogeneity of each study was also low. The incidence of CIN in the TMZ plus hydration group was 6.6% (53/797), while the incidence of CIN in the control (hydration only) group was 20% (165/814). Pooled analysis of all studies showed TMZ reduced incidence of CIN compared to saline hydration alone (OR risk 0.30, 95% CI 0.21, 0.42, P < .0001). CONCLUSION: TMZ added to hydration reduces CIN in renal insufficiency patients undergoing coronary angiography.


Assuntos
Injúria Renal Aguda/prevenção & controle , Angioplastia/efeitos adversos , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Insuficiência Renal Crônica/complicações , Trimetazidina/uso terapêutico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Meios de Contraste/farmacocinética , Angiografia Coronária/métodos , Doença das Coronárias/complicações , Doença das Coronárias/diagnóstico , Doença das Coronárias/cirurgia , Taxa de Filtração Glomerular/fisiologia , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento
17.
Oxid Med Cell Longev ; 2021: 6622232, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728022

RESUMO

Mitochondrial fatty acid oxidation (FAO) is involved in myocardial damage after cardiopulmonary resuscitation (CPR). This study is aimed at investigating the effect of inhibiting mitochondrial FAO on myocardial injury and the underlying mechanisms of postresuscitation myocardial dysfunction. Rats were induced, subjected to 8 min of ventricular fibrillation, and underwent 6 min of CPR. Rats with return of spontaneous circulation (ROSC) were randomly divided into the Sham group, CPR group, and CPR + Trimetazidine (TMZ) group. Rats in the CPR + TMZ group were administered TMZ (10 mg/kg) at the onset of ROSC via the right external jugular vein, while rats in the CPR group were injected with equivalent volumes of vehicle. The sham rats were only administered equivalent volumes of vehicle. We found that the activities of enzymes related to cardiac mitochondrial FAO were partly improved after ROSC. TMZ, as a reversible inhibitor of 3-ketoacyl CoA thiolase, inhibited myocardial mitochondrial FAO after ROSC. In the CPR + TMZ group, the levels of mitochondrial injury in cardiac tissue were alleviated following attenuated myocardial damage and oxidative stress after ROSC. In addition, the disorder of cardiac mitochondrial metabolism was ameliorated, and specifically, the superfluous succinate related to mitochondrial reactive oxygen species (ROS) generation was decreased by inhibiting myocardial mitochondrial FAO with TMZ administration after ROSC. In conclusion, in the early period after ROSC, inhibiting cardiac mitochondrial FAO attenuated excessive cardiac ROS generation and preserved myocardial function, probably by alleviating the dysfunction of cardiac mitochondrial metabolism in a rat model of cardiac arrest.


Assuntos
Ácidos Graxos/metabolismo , Parada Cardíaca/patologia , Mitocôndrias Cardíacas/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Animais , Modelos Animais de Doenças , Parada Cardíaca/tratamento farmacológico , Parada Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Retorno da Circulação Espontânea/efeitos dos fármacos , Trimetazidina/farmacologia , Trimetazidina/uso terapêutico
18.
J Clin Invest ; 131(1)2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393495

RESUMO

Metabolic reprogramming is a common hallmark of cancer, but a large variability in tumor bioenergetics exists between patients. Using high-resolution respirometry on fresh biopsies of human lung adenocarcinoma, we identified 2 subgroups reflected in the histologically normal, paired, cancer-adjacent tissue: high (OX+) mitochondrial respiration and low (OX-) mitochondrial respiration. The OX+ tumors poorly incorporated [18F]fluorodeoxy-glucose and showed increased expression of the mitochondrial trifunctional fatty acid oxidation enzyme (MTP; HADHA) compared with the paired adjacent tissue. Genetic inhibition of MTP altered OX+ tumor growth in vivo. Trimetazidine, an approved drug inhibitor of MTP used in cardiology, also reduced tumor growth and induced disruption of the physical interaction between the MTP and respiratory chain complex I, leading to a cellular redox and energy crisis. MTP expression in tumors was assessed using histology scoring methods and varied in negative correlation with [18F]fluorodeoxy-glucose incorporation. These findings provide proof-of-concept data for preclinical, precision, bioenergetic medicine in oxidative lung carcinomas.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/enzimologia , Subunidade alfa da Proteína Mitocondrial Trifuncional , Proteínas de Neoplasias , Trimetazidina/farmacologia , Linhagem Celular Tumoral , Complexo I de Transporte de Elétrons/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Subunidade alfa da Proteína Mitocondrial Trifuncional/antagonistas & inibidores , Subunidade alfa da Proteína Mitocondrial Trifuncional/biossíntese , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/biossíntese , Oxirredução
19.
Angiology ; 72(6): 511-523, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33472383

RESUMO

We systematically searched the literature to assess the efficacy of trimetazidine in reducing periprocedural myocardial injury and improving postoperative left ventricular ejection fraction (LVEF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). An electronic search was conducted based on the PubMed, Ovid, Scopus, Springer, CENTRAL, and Google Scholar databases; 14 randomized controlled trials (RCTs) were included. Our meta-analysis showed a significant reduction in cardiac troponin I (cTnI) levels with trimetazidine compared with controls (P < .00001) but not in serum creatine kinase-myocardial band levels (P = .49). There were significantly reduced odds of ischemic ST-T segment changes with trimetazidine (P = .0.03) but lack of significant difference in the incidence of anginal attacks between the 2 groups (P = .10). Results also suggest significantly higher LVEF with trimetazidine compared with controls (P < .00001). Meta-regression analysis indicated no influence of duration of trimetazidine therapy on cTnI levels. The administration of preprocedure trimetazidine may have a role in reducing periprocedural myocardial injury in patients with CAD undergoing PCI. Evidence also suggests that postoperative trimetazidine may improve LVEF in the short term. Lack of high-quality trials and the heterogeneity of studies limit the ability of our analysis to draw strong conclusions. Further well-designed RCTs are required to supplement current evidence.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doença da Artéria Coronariana/terapia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Intervenção Coronária Percutânea , Volume Sistólico/efeitos dos fármacos , Trimetazidina/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Biomarcadores/sangue , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/diagnóstico , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Intervenção Coronária Percutânea/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Fatores de Risco , Resultado do Tratamento , Trimetazidina/efeitos adversos , Troponina I/sangue
20.
J Recept Signal Transduct Res ; 41(2): 170-179, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32757698

RESUMO

Previous studies demonstrated the effect of Trimetazidine (TMZ) on alleviating cardiomyocytes Hypoxia/Reoxygenation (H/R) injuries and the protective effect of autophagy on Ischemia-Reperfusion (I/R) cell injuries. However, whether the protection mechanism of TMZ was also involved in autophagy remained unclear. Our study introduces the role of HMGB1 to examine the regulation of TMZ on autophagy against cardiomyocytes H/R injuries. After cell extraction and identification through anti-α-actin staining, the cardiomyocytes were made hypoxic and reoxygenated, each for 3 h, and then treated with various concentrations of TMZ and transfected with siHMGB1. Cell viability and apoptosis were measured by the MTS method and flow cytometry, respectively. The expressions of autophagy-related factors (LC3-I, LC3-II, Beclin-1) and HMGB1 were detected by Western blot and qPCR. Lactate dehydrogenase (LDH) release was assessed by ELISA kit. The cardiomyocytes were extracted. H/R decreased the cell viability and increased the LDH level and apoptosis of cardiomyocytes. TMZ had no effect on untreated cardiomyocytes, but it reversed the adverse impact of H/R on cardiomyocytes. The expressions of LC3-II, Beclin-1, and HMGB1 and the ratio of LC3-II/LC3-I were increased in H/R-processed cardiomyocytes and further raised by TMZ pretreatment. However, siHMGB1 transfection aggravated the impact of H/R on cardiomyocytes and suppressed the protective effects of TMZ on H/R damaged cardiomyocytes by increasing the LDH level and apoptosis and reducing the viability of cardiomyocytes. Autophagy was inhibited by siHMGB1 in TMZ-pretreated and H/R-processed cardiomyocytes. TMZ protected cardiomyocytes against H/R injuries may through regulating HMGB1 to increase the impact of autophagy.


Assuntos
Proteína Beclina-1/genética , Proteína HMGB1/genética , Proteínas Associadas aos Microtúbulos/genética , Traumatismo por Reperfusão/tratamento farmacológico , Trimetazidina/farmacologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Autofagia/genética , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos
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