Background And Aims: Peroxisome proliferator-activated receptor-α (PPAR-α) activation has been reported to reduce myocardial ischemia-reperfusion (I/R) injury by inhibiting cell apoptosis. However, the antiapoptotic mechanism of PPAR-α is still unknown. Fenofibrate is a PPAR-α agonist In the present study, we investigate the effects and relevant mechanism of fenofibrate on experimental myocardial ischemia-reperfusion (I/R) injury in rats.
Methods: Adult male Wistar rats were pretreated with fenofibrate (80 mg/kg) daily for a period of 7 days. After the treatment period, myocardial I/R injury model was made by left anterior descending coronary artery ligation for 45 min and reperfusion for 120 min. Myocardial infarct size, malondialdehyde (MDA) cleaved-caspase-9 protein expression, PPARα and uncoupling protein 2 (UCP2) mRNA levels in myocardial tissue were detected Cell apoptosis was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Serum lactate dehydrogenase and creatine kinase activities were measured in rats pretreated with fenofibrate The ultrastructure of myocardial tissues was observed.
Results: Significant increases in myocardial cell apoptosis, malondialdehyde (MDA) level and cleaved-caspase-9 protein expression level in myocardial tissue were observed, along with reductions of PPARα and uncoupling protein 2 (UCP2) mRNA levels in myocardial tissue of the experimental myocardial ischemia-reperfusion (I/R) injury in rats. Impaired mitochondria were also observed under electron microscopic. However, pretreatment of ischemia/reperfusion rats with fenofibrate brought the biochemical parameters and related genes expression levels to near normalcy, indicating the protective effect of fenofibrate against myocardial ischemia/reperfusion injury in rats.
Conclusions: The PPAR-α activator fenofibrate conferred cytoprotective effect against myocardial ischemia-reperfusion (I/R) injury in rats. Associated mechanisms involved decreased cleaved-caspase-9 expression and decreased cell apoptosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3233/CBM-170572 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
p38γ modulates ferroptosis in brain injury caused by ethanol and cerebral ischemia/reperfusion by regulating the p53/SLC7A11 signaling pathway.
Cell Signal
March 2025
Department of Neurology, Northwest University School of Medicine, Xi'an 710068, China; Northwest University First Hospital, Xi'an 710043, China. Electronic address:
Ischemic stroke, a neurological condition with a complicated etiology that is accompanied by severe inflammation and oxidative stress, and ethanol (EtOH) may aggravate ischemia/reperfusion (I/R)-induced brain damage. However, the effect of prolonged alcohol intake on acute brain injury remains ambiguous. As part of the mitogen-activated protein kinase (MAPK) family, p38γ is involved in ferroptosis and inflammation in various diseases.
View Article and Find Full Text PDFEffective transcatheter intracoronary delivery of mRNA-lipid nanoparticles targeting the heart.
J Control Release
March 2025
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan; Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), Osaka University, Osaka, Japan. Electronic address:
Messenger RNA (mRNA) has great potential to provide innovative medical solutions in the treatment of heart failure. Although lipid nanoparticles (LNPs) are an established mRNA delivery system, effectively delivering LNPs to the heart remains a significant challenge. Here, we evaluated the efficacy of transcatheter intracoronary (IC) administration compared to intravenous (IV) and intramyocardial (IM) administration in normal and ischemia-reperfusion (I/R) model rabbit hearts using LNPs encapsulating Firefly Luciferase (FLuc) mRNA.
View Article and Find Full Text PDFNicotinamide mononucleotide supplementation ameliorates testicular damage induced by ischemia-reperfusion through reshaping macrophage and neutrophil inflammatory properties.
Int Immunopharmacol
March 2025
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address:
Background: Ischemia-reperfusion (I/R) injury is the main pathophysiology of testicular torsion-detorsion (T/D). However, there is no safe and effective treatment for testicular I/R injury.
Methods: The levels of NAD related genes were measured in the sham group, I/R + saline-treated group, and I/R + NMN-treated group by quantitative reverse transcription PCR (qRT-PCR).
Enhanced FGF21 Delivery via Neutrophil-Membrane-Coated Nanoparticles Improves Therapeutic Efficacy for Myocardial Ischemia-Reperfusion Injury.
Nanomaterials (Basel)
February 2025
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Acute myocardial infarction, a leading cause of death globally, is often associated with cardiometabolic disorders such as atherosclerosis and metabolic syndrome. Metabolic treatment of these disorders can improve cardiac outcomes, as exemplified by the GLP-1 agonist semaglutide. Fibroblast growth factor 21 (FGF21), a novel metabolic regulator, plays pivotal roles in lipid mobilization and energy conversion, reducing lipotoxicity, inflammation, mitochondrial health, and subsequent tissue damage in organs such as the liver, pancreas, and heart.
View Article and Find Full Text PDFIdentification of regulator gene and pathway in myocardial ischemia-reperfusion injury: a bioinformatics and biological validation study.
Hereditas
March 2025
Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Background: Acute myocardial infarction (AMI) is the primary cause of cardiac mortality worldwide. However, myocardial ischemia-reperfusion injury (MIRI) following reperfusion therapy is common in AMI, causing myocardial damage and affecting the patient's prognosis. Presently, there are no effective treatments available for MIRI.
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!