The alpha-tocopherol analogue 3,4-dihydro-6-hydroxy-N,N,N,2,5,7,8- heptamethyl-2H-1-benzopyran-2-ethanaminium 4-methylbenzenesulfonate (1a, MDL 73404) and its O-acetate 1b (MDL 74270) were synthesized. Compound 1a was found to be hydrophilic (log P = -0.60) and to prevent lipid autoxidation in rat brain homogenate with an IC50 of 1.7 +/- 0.9 microM. Tissue distribution studies with [14C]-1b in rats (1 mg/kg iv) showed that radioactivity accumulates in the heart (ratio 20:1 vs blood after 1 h). Infusion of 1 mg/kg per h of 1b bromide reduced infarct size by 54% in rats subjected to coronary artery occlusion for 60 min followed by reperfusion for 30 min, compared to saline-infused controls. By comparison, the tertiary amine analogue 5 was found not to accumulate in heart tissue, to be an equally effective free-radical scavenger in vitro, but to require a higher dose to reduce infarct size in rats. This shows that the cardioselectivity of compound 1 contributes to its potency in salvaging myocardial tissue in rats after ischemia and reperfusion.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm00105a040 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effects of Electroacupuncture Per-Conditioning at Huantiao on Motor Function Recovery in Acute Cerebral Ischemia Mice.
Physiol Behav
January 2025
Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address:
Background: Continuous electroacupuncture pre-conditioning (EPRC) and post-conditioning (EPOC) effectively improve motor dysfunction after acute cerebral ischemia, but they require multiple treatments. Recently, electroacupuncture per-conditioning (EPEC) has demonstrated neuroprotective effects, indicating that this single-session intervention has short-term efficacy.
Objective: To evaluate the effect of EPEC at Huantiao (GB30) on motor recovery in acute cerebral ischemia mice.
The UCP2/PINK1/LC3b-mediated mitophagy is involved in the protection of NRG1 against myocardial ischemia/reperfusion injury.
Redox Biol
January 2025
Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China. Electronic address:
Available evidence indicates that neuregulin-1 (NRG-1) can provide a protection against myocardial ischemia/reperfusion (I/R) injury and is involved in various cardioprotective interventions by potential regulation of mitophagy. However, the molecular mechanisms linking NRG-1 and mitophagy remain to be clarified. In this study, both an in vivo myocardial I/R injury model of rats and an in vitro hypoxia/reoxygenation (H/R) model of H9C2 cardiomyocytes were applied to determine whether NRG-1 postconditioning attenuated myocardial I/R injury through the regulation of mitophagy and to explore the underlying mechanisms.
View Article and Find Full Text PDFHistological differences among thrombi in thrombotic diseases.
Curr Opin Hematol
January 2025
Department of Pathology, Section of Oncopathology and Morphological Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Purpose Of Review: This review aims to summarize the histological differences among thrombi in acute myocardial infarction, ischemic stroke, venous thromboembolism, and amniotic fluid embolism, a newly identified thrombosis.
Recent Findings: Acute coronary thrombi have a small size, are enriched in platelets and fibrin, and show the presence of fibrin and von Willebrand factor, but not collagen, at plaque rupture sites. Symptomatic deep vein thrombi are large and exhibit various phases of time-dependent histological changes.
Mitochondrial transplantation for the treatment of cardiac and noncardiac diseases: mechanisms, prospective, and challenges.
Life Med
April 2024
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Mitochondrial transplantation (MT) is a promising therapeutic strategy that involves introducing healthy mitochondria into damaged tissues to restore cellular function. This approach has shown promise in treating cardiac diseases, such as ischemia-reperfusion injury, myocardial infarction, and heart failure, where mitochondrial dysfunction plays a crucial role. Transplanting healthy mitochondria into affected cardiac tissue has resulted in improved cardiac function, reduced infract size, and enhanced cell survival in preclinical studies.
View Article and Find Full Text PDFBackground: The prevalence of coronary chronic total occlusion (CTO) in coronary angiography (CAG) has risen with ageing populations, along with the expansion of CTO percutaneous coronary interventions (CTO-PCI). However, CTO-PCI encounters challenges such as undersized stents, dissection risks, and limited access to intravascular imaging (IVI), particularly in regions with limited health budgets. This study introduces the 'GIVE IT TIME TO SOBER UP - GITSU strategy', a two-session CTO-PCI approach where Thrombolysis in Myocardial Infarction (TIMI-3) antegrade flow is achieved without stent placement in the first session.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!