Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (27)

Search Parameters:
Keywords = trimetazidine

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
20 pages, 2548 KiB  
Article
In Vitro Metabolism of Doping Agents (Stanozolol, LGD-4033, Anastrozole, GW1516, Trimetazidine) by Human Seminal Vesicle and Liver Fractions
by Johanna Sternberg, Insa Peters, Nana Naumann, Andreas Thomas and Mario Thevis
Metabolites 2025, 15(7), 452; https://doi.org/10.3390/metabo15070452 - 4 Jul 2025
Viewed by 495
Abstract
Background: In order to address complex scenarios in anti-doping science, especially in cases where an unintentional exposure of athletes to prohibited substances and a corresponding contamination of doping control samples at the collection event are argued, an understanding of tissue-specific drug metabolism is [...] Read more.
Background: In order to address complex scenarios in anti-doping science, especially in cases where an unintentional exposure of athletes to prohibited substances and a corresponding contamination of doping control samples at the collection event are argued, an understanding of tissue-specific drug metabolism is essential. Hence, in this study, the metabolic capacity of the seminal vesicle using in vitro assays was investigated. Methods: The aim was to assess whether selected doping-relevant substances—stanozolol, LGD-4033, GW1516, trimetazidine, and anastrozole—are metabolised in seminal vesicle cellular fractions (SV-S9) and how that metabolism compares to biotransformations induced by human liver S9 fractions (HL-S9). Liquid chromatography coupled to high-resolution/accurate mass spectrometry (LC HRAM MS) enabled the sensitive detection and identification of metabolites, revealing a limited metabolic activity of SV-S9. Results: For LGD-4033, GW1516, and trimetazidine, minor metabolic transformations were observed, whereas no metabolites of stanozolol or anastrozole were detected. Gene expression analysis using digital polymerase chain reaction (dPCR) confirmed transcripts of CYP2D6, CYP2E1, and CYP2C9 in SV-S9, though no enzymatic activity was detected. Gene expression and enzymatic activity in CYP3A4 and CYP1A2—major hepatic enzymes—were absent in SV-S9. Conclusions: Overall, these pilot study results suggest that the seminal vesicle has only a low capacity for xenobiotic metabolism, which translates into a limited role in the biotransformation of drugs and, hence, the metabolic pattern. Full article
(This article belongs to the Section Pharmacology and Drug Metabolism)
Show Figures

Graphical abstract

27 pages, 1213 KiB  
Systematic Review
Treatment Modalities for Angina with Non-Obstructive Coronary Arteries (ANOCA): A Systematic Review and Meta-Analysis
by Fabienne E. Vervaat, Annemiek de Vos, Jimmy Schenk, Pim A. L. Tonino and Inge F. Wijnbergen
J. Clin. Med. 2025, 14(12), 4069; https://doi.org/10.3390/jcm14124069 - 9 Jun 2025
Viewed by 711
Abstract
Background and Objectives: Up to 40% of patients undergoing a coronary angiogram due to angina pectoris have no obstructive coronary artery disease, also known as angina with non-obstructive coronary arteries (ANOCA). ANOCA is associated with significant impairment in patients’ quality of life, increased [...] Read more.
Background and Objectives: Up to 40% of patients undergoing a coronary angiogram due to angina pectoris have no obstructive coronary artery disease, also known as angina with non-obstructive coronary arteries (ANOCA). ANOCA is associated with significant impairment in patients’ quality of life, increased risk of myocardial infarction and all-cause mortality. Approximately 25% of patients with ANOCA have persisting symptoms despite optimal medical therapy. There is a lack of in-depth knowledge regarding tailored treatment for patients with ANOCA due to a scarcity of trials designed to assess the effect of treatment modalities. The aim of this systematic review and meta-analysis is to give clinicians an overview of the efficacy of current treatment modalities for patients with ANOCA. Methods: PudMed/MEDLINE, Embase, the Cochrane Library and clinical trial registries were searched for randomised controlled and cohort studies regarding treatment modalities for ANOCA. The main outcome was change in angina pectoris frequency for each treatment modality. Secondary outcomes included changes in exercise capacity, quality of life, Canadian Cardiovascular Society (CCS) class, coronary flow reserve (CFR) and survival. Results: In total, 80 studies were included and used in the meta-analysis, of which ten studies met the current definition of ANOCA. Angina pectoris frequency improved significantly in the majority of the treatment modalities, with neuromodulation resulting in −3.35 standardised mean difference (SMD) (95% CI: −5.13; −1.56), trimetazidine in −1.74 SMD (−2.63; −0.85), traditional Chinese medicine in −1.55 SMD (−2.36; −0.75), beta-blockers in −1.32 SMD (−1.88; −0.77), enhanced external counterpulsation in −1.27 SMD (−2.04; −0.49), stem cell therapy in −1.04 SMD (−1.51; −0.57), lifestyle interventions in −0.86 SMD (−1.15; −0.57), RAAS-inhibitors in −0.83 SMD (−1.31; −0.35) and calcium channel blockers in −0.64 SMD (−0.92; −0.35). Conclusions: This meta-analysis into treatment modalities for patients with ANOCA shows a significant improvement in angina pectoris frequency in the majority of included treatment modalities. However, these results should be interpreted cautiously, as only ten of the studies included in the meta-analysis meet the current definition of ANOCA. This review underlines the importance of undertaking new studies with existing treatment modalities to determine the efficacy in patients with ANOCA. Full article
Show Figures

Figure 1

17 pages, 258 KiB  
Review
Nutrient-Driven Antioxidant Interventions for Prevention of Age-Related and Diabetic Cataracts
by Rosa Giglio, Serena Milan, Leandro Inferrera, Daniele Tognetto, Fabiana D’Esposito, Federico Visalli, Caterina Gagliano and Marco Zeppieri
Nutrients 2025, 17(11), 1885; https://doi.org/10.3390/nu17111885 - 30 May 2025
Viewed by 505
Abstract
Cataract formation remains a significant cause of global visual impairment. Increasing attention has been directed toward antioxidant-based interventions as potential non-surgical strategies to delay or prevent cataractogenesis, particularly in the age-related and diabetic contexts. This review summarizes recent preclinical evidence on nutritional antioxidants [...] Read more.
Cataract formation remains a significant cause of global visual impairment. Increasing attention has been directed toward antioxidant-based interventions as potential non-surgical strategies to delay or prevent cataractogenesis, particularly in the age-related and diabetic contexts. This review summarizes recent preclinical evidence on nutritional antioxidants for the prevention of age-related and diabetic cataracts. Agents such as trimetazidine, Moringa oleifera stem extract, ginsenoside Rg1, lanosterol nanoparticles, β-casomorphin-7, and cerium oxide-based nanotherapies have been shown to mitigate oxidative damage, modulate redox signaling pathways, and preserve lens clarity. Advances in drug delivery, including topical formulations, nanoparticle carriers, and intravitreal injections, have been proposed to overcome the anatomical and pharmacokinetic barriers associated with the avascular lens. The new data support ongoing translational research to maximize the clinical use of antioxidants and highlight their therapeutic potential in the prevention of age-related and diabetic cataracts. Full article
(This article belongs to the Special Issue Diet and Supplements in the Prevention and Treatment of Eye Diseases)
21 pages, 4032 KiB  
Article
Cardioprotective Effects of Dapagliflozin and Trimetazidine on Doxorubicin-Induced Cardiotoxicity in Streptozotocin-Induced Type 1 Diabetic Rats via Endoplasmic Reticulum Stress
by Muhammed Mursel Ogutveren, Omer Satiroglu, Zulkar Ozden, Kerimali Akyildiz, Adnan Yilmaz, Filiz Mercantepe, Ahmet Seyda Yilmaz, Haldun Koc and Tolga Mercantepe
J. Clin. Med. 2025, 14(4), 1315; https://doi.org/10.3390/jcm14041315 - 16 Feb 2025
Cited by 1 | Viewed by 1055
Abstract
Background/Objectives: Diabetic cardiomyopathy is a distinct myocardial dysfunction characterized by structural and functional changes in the heart that occur in diabetic patients independently of coronary artery disease or hypertension. It is closely associated with oxidative stress, inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) [...] Read more.
Background/Objectives: Diabetic cardiomyopathy is a distinct myocardial dysfunction characterized by structural and functional changes in the heart that occur in diabetic patients independently of coronary artery disease or hypertension. It is closely associated with oxidative stress, inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress, and contributes to progressive cardiac damage. This study aimed to evaluate the cardioprotective effects of dapagliflozin (DAPA) and trimetazidine (TMZ) in a rat model of doxorubicin-induced cardiomyopathy with streptozotocin-induced diabetes, focusing on their potential mechanisms related to ER stress. Methods: A total of 48 Sprague Dawley rats aged 6–8 weeks were randomly distributed equally into six cages. The diabetes model was induced by intraperitoneal administration of streptozotocin (STZ) and rats with blood glucose levels above 250 mg/dL were considered diabetic. For those rats with diabetes, cardiotoxicity was induced by intraperitoneal injection of 5 mg/kg/week doxorubicin (DOXO) for 4 weeks. After a cumulative dose of 20 mg/kg doxorubicin, a week break was given, followed by the administration of TMZ (10 mg/kg) and/or DAPA (10 mg/kg) to the treatment groups. Results: STZ administration caused diabetes and significant degeneration in cardiomyocytes. With the addition of DOXO (STZ + DOXO), cardiomyocyte degeneration became more severe. When the study groups were histopathologically evaluated based on parameters of degenerative cardiomyocytes, vascular congestion, and edema, it was shown that both TMZ and DAPA, whether applied alone or in combination, reduced damage in heart tissue. Both TMZ and DAPA reduced cardiomyocyte damage, and their combination provided the lowest level of damage through the reduced ER stress pathway by reducing GRP 78 and CHOP positivity. Conclusions: TMZ and DAPA reduce ER stress and have protective effects against diabetic-induced cardiotoxicity. Combination therapy or TMZ was found to be more effective than DAPA in alleviating ER stress. Combination therapy appears to carry potential effects for reducing cardiac cell damage in individuals with diabetes. Full article
Show Figures

Figure 1

18 pages, 8743 KiB  
Article
Highly Sensitive Trimetazidine Determination Using Composite Yttria-Stabilized Zirconia Doped with Titanium Oxide–Carbon Black Biosensor
by Małgorzata Suchanek, Agata Krakowska, Beata Paczosa-Bator and Robert Piech
Materials 2024, 17(22), 5556; https://doi.org/10.3390/ma17225556 - 14 Nov 2024
Cited by 1 | Viewed by 1133
Abstract
A novel composite voltammetric biosensor has been developed for the first time, utilizing a glassy carbon electrode modified with yttria-stabilized zirconia doped with titanium dioxide and carbon black (YSZTiO2-CB/GCE), specifically designed for the detection of trimetazidine (TMZ). The measurement conditions, including [...] Read more.
A novel composite voltammetric biosensor has been developed for the first time, utilizing a glassy carbon electrode modified with yttria-stabilized zirconia doped with titanium dioxide and carbon black (YSZTiO2-CB/GCE), specifically designed for the detection of trimetazidine (TMZ). The measurement conditions, including both the supporting electrolyte and instrumental settings, were optimized to enhance performance. In the concentration range of 0.5 to 7 µM, it is not necessary to use preconcentration time for the determination of TMZ. The limit of detection (for 60 s of preconcentration time) was equal to 5.5 nM (1.87 ng mL−1), outperforming other voltammetric methods in terms of sensitivity. The reproducibility of the trimetazidine signal (with a concentration of 0.05 µM) exhibited a relative standard deviation (RSD) of 3.3% over 10 measurements. Additionally, our biosensor is characterized by excellent stability, ease of use, and straightforward preparation. The proposed biosensor and method have proven effective in analyzing TMZ in a variety of matrices, including urine, blood plasma, pharmaceutical formulations, as well as gastric and intestinal fluids, yielding recovery rates ranging from 97.7 to 102.3%. Full article
Show Figures

Figure 1

18 pages, 22851 KiB  
Article
Protective Effects of Trimetazidine and Dexmedetomidine on Liver Injury in a Mesenteric Artery Ischemia–Reperfusion Rat Model via Endoplasmic Reticulum Stress
by Sedat Ciftel, Tolga Mercantepe, Riza Aktepe, Esra Pinarbas, Zulkar Ozden, Adnan Yilmaz and Filiz Mercantepe
Biomedicines 2024, 12(10), 2299; https://doi.org/10.3390/biomedicines12102299 - 10 Oct 2024
Cited by 2 | Viewed by 1613
Abstract
Background/Objectives: Acute mesenteric ischemia can lead to severe liver damage due to ischemia–reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Methods: Twenty-four [...] Read more.
Background/Objectives: Acute mesenteric ischemia can lead to severe liver damage due to ischemia–reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Methods: Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels. Results: Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments. Conclusions: Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ. Full article
(This article belongs to the Special Issue Hepatotoxicity: From Pathology to Novel Therapeutic Approaches)
Show Figures

Figure 1

5 pages, 778 KiB  
Communication
Synthesis of Novel Sulfonamide Derivatives Featuring 1-(Methylsulfonyl)-4-(2,3,4-Trimethoxybenzyl)Piperazine Core Structures
by Iliyan Ivanov, Stanimir Manolov, Dimitar Bojilov, Diyana Dimitrova and Paraskev Nedialkov
Molbank 2024, 2024(3), M1879; https://doi.org/10.3390/M1879 - 9 Sep 2024
Viewed by 1933
Abstract
Herein we report the synthesis of three novel sulfonamide derivatives of trimetazidine—medication primarily used to treat angina pectoris. The new compounds have been fully characterized with their melting point, 1H- and 13C-NMR, UV, and mass spectrometry. The collected data confirm the [...] Read more.
Herein we report the synthesis of three novel sulfonamide derivatives of trimetazidine—medication primarily used to treat angina pectoris. The new compounds have been fully characterized with their melting point, 1H- and 13C-NMR, UV, and mass spectrometry. The collected data confirm the successful synthesis and structural integrity of the new molecules. Full article
(This article belongs to the Section Organic Synthesis and Biosynthesis)
Show Figures

Figure 1

21 pages, 10510 KiB  
Article
Evaluation of Endoplasmic Reticulum Stress in an Experimental Intestinal Ischemia–Reperfusion Model in Rats: The Role of Ozone Therapy and Trimetazidine
by Gokhan Demiral, Tolga Mercantepe, Gurkan Altuntas, Ahmet Pergel, Suleyman Kalcan, Ali Ozdemir, Levent Tumkaya, Sibel Mataraci Karakas, Aykut Ozturk and Adnan Yilmaz
Biomolecules 2024, 14(9), 1051; https://doi.org/10.3390/biom14091051 - 25 Aug 2024
Viewed by 1824
Abstract
Aim: The objective of the study was to assess the impact of ozone (O3) and trimetazidine on the intestines following ischemia–reperfusion (I/R) injury through the investigation of endoplasmic reticulum stress. Methods: Forty Sprague Dawley rats were separated into five groups. The [...] Read more.
Aim: The objective of the study was to assess the impact of ozone (O3) and trimetazidine on the intestines following ischemia–reperfusion (I/R) injury through the investigation of endoplasmic reticulum stress. Methods: Forty Sprague Dawley rats were separated into five groups. The groups were named as follows: control, O3, I/R, I/R + trimetazidine (TMZ), and I/R + O3. The control group had laparotomy and exploration of the superior mesenteric artery (SMA) only. Furthermore, alongside laparotomy and SMA exploration, an intraperitoneal (i.p.) administration of a 0.7 mg/kg ozone–oxygen (O3-O2) combination was given to the O3 group. In the experimental groups, the SMA was blocked with the silk suture ligation technique for a duration of 1 h and then restored to normal blood flow for another hour. In the I/R + O3 group, ozone was delivered i.p. at a dosage of 0.7 mg/kg, 30 min after ischemia. In the I/R + TMZ group, a dose of 20 mg/kg/day of trimetazidine was administered orally via gavage for a duration of 7 days, beginning 1 week prior to the induction of ischemia. Intestinal tissues were taken to assess indicators of intestinal mucosal injury and oxidative stress. Results: The level of the lipid peroxidation marker malondialdehyde (MDA) was significantly reduced in the experimental groups as compared to the I/R group (p < 0.05). The experimental groups had considerably greater levels of glutathione (GSH), which reflects antioxidant capacity, compared to the I/R group (p < 0.05). Nevertheless, the concentration of GSH was observed to be increased in the I/R + O3 group in comparison to the I/R + TMZ group (p < 0.05). The histopathological damage score showed a substantial decrease in the experimental groups as compared to the I/R group (p < 0.05). The I/R + O3 group had the lowest injury score. The experimental groups exhibited significantly reduced positivity of the endoplasmic reticulum (ER) stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78 compared to the I/R group (p < 0.05). Conclusions: The findings provide evidence for the potential advantages of utilizing ozone therapy in the treatment of intestinal ischemia–reperfusion injury. Additionally, they propose that ozone should be assessed in more extensive clinical trials in the future as a therapeutic agent that can disrupt endoplasmic reticulum stress. Full article
Show Figures

Figure 1

13 pages, 1276 KiB  
Systematic Review
Efficacy of Trimetazidine in the Prevention of Contrast-Induced Nephropathy in Patients Undergoing Contrast Coronary Intervention: A Systematic Review and Meta-Analysis (PRISMA)
by Tiny Nair, Saumitra Ray, Jacob George and Arindam Pande
J. Clin. Med. 2024, 13(7), 2151; https://doi.org/10.3390/jcm13072151 - 8 Apr 2024
Cited by 2 | Viewed by 2415
Abstract
Objective: The present systematic review assessed the efficacy of peri-procedurally administered trimetazidine in the prevention of contrast-induced nephropathy (CIN) in patients undergoing coronary interventions with contrast agents. Methods: We performed a systematic literature review of articles published in PubMed and Google [...] Read more.
Objective: The present systematic review assessed the efficacy of peri-procedurally administered trimetazidine in the prevention of contrast-induced nephropathy (CIN) in patients undergoing coronary interventions with contrast agents. Methods: We performed a systematic literature review of articles published in PubMed and Google Scholar by 7 December 2023 and included articles from the last 15 years that evaluated the efficacy of trimetazidine in preventing CIN in cardiac patients undergoing coronary intervention. Results: After title/abstract and full-text screening, this systematic review included 9 randomized controlled trials (N = 2158 patients) with two groups: Trimetazidine (60–70 mg/day 24 to 48 h before and up to 72 h after the procedure) with hydration and the control group with only hydration. A total of 234/2158 patients developed CIN (Incidence rate [IR], 10.8%) as per the CIN definition of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The incidence of CIN in the trimetazidine vs. control group was 6.4% (69/1083) vs. 15.4% (165/1075), and the odds ratio (95% CI) was 0.3753 (0.279–0.504). Conclusions: In conclusion, the trimetazidine group had a lower incidence of CIN. Trimetazidine offers a reno-protective effect and helps in reducing the CIN incidence in patients undergoing cardiac intervention. Peri-procedure administration of trimetazidine significantly decreases the risk of CIN in patients despite comorbidities. Full article
(This article belongs to the Section Cardiology)
Show Figures

Figure 1

21 pages, 820 KiB  
Review
Role of Trimetazidine in Ameliorating Endothelial Dysfunction: A Review
by Yusof Kamisah and Hamat H. Che Hassan
Pharmaceuticals 2024, 17(4), 464; https://doi.org/10.3390/ph17040464 - 5 Apr 2024
Cited by 5 | Viewed by 3105
Abstract
Endothelial dysfunction is a hallmark of cardiovascular diseases, contributing to impaired vasodilation, altered hemodynamics, and atherosclerosis progression. Trimetazidine, traditionally used for angina pectoris, exhibits diverse therapeutic effects on endothelial dysfunction. This review aims to elucidate the mechanisms underlying trimetazidine’s actions and its potential [...] Read more.
Endothelial dysfunction is a hallmark of cardiovascular diseases, contributing to impaired vasodilation, altered hemodynamics, and atherosclerosis progression. Trimetazidine, traditionally used for angina pectoris, exhibits diverse therapeutic effects on endothelial dysfunction. This review aims to elucidate the mechanisms underlying trimetazidine’s actions and its potential as a therapeutic agent for endothelial dysfunction and associated cardiovascular disorders. Trimetazidine enhances vasodilation and hemodynamic function by modulating endothelial nitric oxide synthase activity, nitric oxide production, and endothelin-1. It also ameliorates metabolic parameters, including reducing blood glucose, mitigating oxidative stress, and dampening inflammation. Additionally, trimetazidine exerts antiatherosclerotic effects by inhibiting plaque formation and promoting its stability. Moreover, it regulates apoptosis and angiogenesis, fostering endothelial cell survival and neovascularization. Understanding trimetazidine’s multifaceted mechanisms underscores its potential as a therapeutic agent for endothelial dysfunction and associated cardiovascular disorders, warranting further investigation for clinical translation. Full article
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—Advances in Pharmacology)
Show Figures

Figure 1

21 pages, 4465 KiB  
Article
Trimetazidine Improves Mitochondrial Dysfunction in SOD1G93A Cellular Models of Amyotrophic Lateral Sclerosis through Autophagy Activation
by Illari Salvatori, Valentina Nesci, Alida Spalloni, Veronica Marabitti, Maurizio Muzzi, Henri Zenuni, Silvia Scaricamazza, Marco Rosina, Gianmarco Fenili, Mariangela Goglia, Laura Boffa, Roberto Massa, Sandra Moreno, Nicola Biagio Mercuri, Francesca Nazio, Patrizia Longone, Alberto Ferri and Cristiana Valle
Int. J. Mol. Sci. 2024, 25(6), 3251; https://doi.org/10.3390/ijms25063251 - 13 Mar 2024
Cited by 3 | Viewed by 2968
Abstract
Amyotrophic Lateral Sclerosis (ALS) is considered the prototype of motor neuron disease, characterized by motor neuron loss and muscle waste. A well-established pathogenic hallmark of ALS is mitochondrial failure, leading to bioenergetic deficits. So far, pharmacological interventions for the disease have proven ineffective. [...] Read more.
Amyotrophic Lateral Sclerosis (ALS) is considered the prototype of motor neuron disease, characterized by motor neuron loss and muscle waste. A well-established pathogenic hallmark of ALS is mitochondrial failure, leading to bioenergetic deficits. So far, pharmacological interventions for the disease have proven ineffective. Trimetazidine (TMZ) is described as a metabolic modulator acting on different cellular pathways. Its efficacy in enhancing muscular and cardiovascular performance has been widely described, although its molecular target remains elusive. We addressed the molecular mechanisms underlying TMZ action on neuronal experimental paradigms. To this aim, we treated murine SOD1G93A-model-derived primary cultures of cortical and spinal enriched motor neurons, as well as a murine motor-neuron-like cell line overexpressing SOD1G93A, with TMZ. We first characterized the bioenergetic profile of the cell cultures, demonstrating significant mitochondrial dysfunction that is reversed by acute TMZ treatments. We then investigated the effect of TMZ in promoting autophagy processes and its impact on mitochondrial morphology. Finally, we demonstrated the effectiveness of TMZ in terms of the mitochondrial functionality of ALS-rpatient-derived peripheral blood mononuclear cells (PBMCs). In summary, our results emphasize the concept that targeting mitochondrial dysfunction may represent an effective therapeutic strategy for ALS. The findings demonstrate that TMZ enhances mitochondrial performance in motor neuron cells by activating autophagy processes, particularly mitophagy. Although further investigations are needed to elucidate the precise molecular pathways involved, these results hold critical implications for the development of more effective and specific derivatives of TMZ for ALS treatment. Full article
(This article belongs to the Special Issue Role of Mitochondria in Diseases)
Show Figures

Figure 1

11 pages, 678 KiB  
Article
Implementation of Microcirculation Examination in Clinical Practice—Insights from the Nationwide POL-MKW Registry
by Rafał Januszek, Łukasz Kołtowski, Mariusz Tomaniak, Wojciech Wańha, Wojciech Wojakowski, Marek Grygier, Wojciech Siłka, Grzegorz Jan Horszczaruk, Bartosz Czarniak, Radosław Kręcki, Bartłomiej Guzik, Jacek Legutko, Tomasz Pawłowski, Paweł Wnęk, Marek Roik, Sylwia Sławek-Szmyt, Miłosz Jaguszewski, Tomasz Roleder, Miłosz Dziarmaga and Stanisław Bartuś
Medicina 2024, 60(2), 277; https://doi.org/10.3390/medicina60020277 - 5 Feb 2024
Viewed by 1823
Abstract
Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients’ clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve [...] Read more.
Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients’ clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often. Full article
Show Figures

Figure 1

16 pages, 2784 KiB  
Review
Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review
by Amalia Pușcaș, Ruxandra Ștefănescu, Camil-Eugen Vari, Bianca-Eugenia Ősz, Cristina Filip, Jana Karlina Bitzan, Mădălina-Georgiana Buț and Amelia Tero-Vescan
Int. J. Mol. Sci. 2024, 25(3), 1605; https://doi.org/10.3390/ijms25031605 - 28 Jan 2024
Cited by 8 | Viewed by 4296
Abstract
Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of [...] Read more.
Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium’s ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge. Full article
(This article belongs to the Section Molecular Pharmacology)
Show Figures

Figure 1

18 pages, 3919 KiB  
Article
Treatment of Antihypertensive and Cardiovascular Drugs in Supercritical Water: An Experimental and Modeled Approach
by Isabela M. Dias, Lucas C. Mourão, Guilherme B. M. De Souza, Jose M. Abelleira-Pereira, Julles M. Dos Santos-Junior, Antônio C. D. De Freitas, Lucio Cardozo-Filho, Christian G. Alonso and Reginaldo Guirardello
Water 2024, 16(1), 125; https://doi.org/10.3390/w16010125 - 29 Dec 2023
Cited by 3 | Viewed by 1855
Abstract
Pharmaceutical pollutants are considered emerging contaminants, representing a significant concern to the ecosystem. Thus, this study reports on the degradation of antihypertensive and cardiovascular drugs (atenolol, captopril, propranolol hydrochloride, diosmin, hesperidin, losartan potassium, hydrochlorothiazide, and trimetazidine) present in simulated wastewater through applying the [...] Read more.
Pharmaceutical pollutants are considered emerging contaminants, representing a significant concern to the ecosystem. Thus, this study reports on the degradation of antihypertensive and cardiovascular drugs (atenolol, captopril, propranolol hydrochloride, diosmin, hesperidin, losartan potassium, hydrochlorothiazide, and trimetazidine) present in simulated wastewater through applying the technology of oxidation using supercritical water (SCW). The operational parameters of the treatment process, particularly the feed flow rate, temperature, and concentration of H2O2, were assessed. A central composite design of experiments associated with differential evolution was employed in the optimization. Both liquid and gaseous phase products were submitted to physical–chemical characterization. As a result, the optimized conditions for the treatment were discovered to be a feed flow rate of 13.3 mL/min, a temperature of 600 °C, and a H2O2 oxidation coefficient of 0.65, corresponding to the oxygen stoichiometric coefficient in the carbon oxidation chemical reaction. Under optimal conditions, the total organic carbon (TOC) decreased from 332 to 25 mg/L (92.1%), and the pharmaceutical molecules underwent near-complete degradation. The physical–chemical parameters also met with the main environmental regulations for wastewater disposal. The compounds determined in the gaseous phase were CO2 (97.9%), H2 (1.3%), CH4 (0.3%), and CO (0.5%.). Additionally, a modeling thermodynamic equilibrium of the system was performed, based on the experimental data. The results revealed that SCW technology has a great potential to oxidize/degrade organic matter and can be applied to treat pharmaceutical pollutants. Full article
Show Figures

Graphical abstract

20 pages, 929 KiB  
Review
Metabolic Approaches for the Treatment of Dilated Cardiomyopathy
by Roberto Spoladore, Giuseppe Pinto, Francesca Daus, Sara Pezzini, Damianos Kolios and Gabriele Fragasso
J. Cardiovasc. Dev. Dis. 2023, 10(7), 287; https://doi.org/10.3390/jcdd10070287 - 5 Jul 2023
Cited by 9 | Viewed by 4029
Abstract
In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a [...] Read more.
In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). However, for unidentified reasons, none of these drugs has ever been tested in a clinical trial of sufficient size. Other pilot studies came to the conclusion that because the heart in severe dilated cardiomyopathy appears to be metabolically flexible and not limited by oxygen, the current rationale for increasing glucose oxidation as a therapeutic target is contradicted and increasing fatty acid oxidation is supported. As a result, treating metabolic dysfunction in HF may benefit from raising ketone body levels. Interestingly, treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves cardiac function and outcomes in HF patients with or without type 2 diabetes mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone body levels. The improvement in overall cardiac function seen in patients receiving SGLT2i could be explained by this increase, which appears to be a reflection of an adaptive process that optimizes cardiac energy metabolism. This review aims to identify the best metabolic therapeutic approach for DCM patients, to examine the drugs that directly affect cardiac metabolism, and to outline all the potential ancillary metabolic effects of the guideline-directed medical therapy. In addition, a special focus is placed on SGLT2i, which were first studied and prescribed to diabetic patients before being successfully incorporated into the pharmacological arsenal for HF patients. Full article
Show Figures

Figure 1

Back to TopTop