Therapeutic Effect of Fimasartan in a Rat Model of Myocardial Infarction Evaluated by Cardiac Positron Emission Tomography with [¹⁸F]FPTP

Abstract

We evaluated the efficacy of fimasartan on perfusion defects and infarction size in an animal model of myocardial infarction (MI), with echocardiography and positron emission tomography (PET) using a 18 F-labeled phosphonium cation (5-[ 18 F]-fluoropentyl-triphenylphosphonium salt, [ 18 F]FPTP) as a mitochondrial voltage sensor for myocardial imaging. We induced MI in 33 rats by ligation of the left coronary artery, and checked their cardiac PET image using [ 18 F]FPTP for evaluation of myocardial perfusion. Rats were grouped into 3 groups according to their administered drugs: no drug (n=11), fimasartan 3 mg/kg (n=10), and fimasartan 10 mg/kg (n=12). Each designated drug was administered for 4 weeks, and follow-up PET and histologic examinations were done. In the PET analysis, a perfusion defect size was markedly improved in fimasartan 10 mg/kg group (35.9±7.0% to 28.4±6.9%, p<0.001), whereas treatment with fimasartan 3 mg/kg induced only an insignificant reduction of perfusion defect size (35.9±7.9% to 33.9±7.3%, p=0.095). Using 2, 3, 5-triphenyltetrazolium chloride staining, infarction size was the largest in the control group (36.5±8.3%), and was insignificantly lower in the fimasartan 3 mg/kg group (31.5±6.5%, p for the difference between the control group=0.146) and was significantly lower in the fimasartan 10 mg/kg group (26.3±7.6%, p for the difference between the control group=0.011). PET imaging using a 18 F-labeled mitochondrial voltage sensor, [ 18 F]FPTP, is useful in evaluation and monitoring of myocardial perfusion states, and treatment with fimasartan decreases the infarction size in animal MI model.

<p>Micelles Loaded With Puerarin And Modified With Triphenylphosphonium Cation Possess Mitochondrial Targeting And Demonstrate Enhanced Protective Effect Against Isoprenaline-Induced H9c2 Cells Apoptosis</p>

“…These mitochondria-targeted drug delivery systems have achieved promising anticancer effects in cancer chemotherapy 16. In addition ( 18 F-Fluoropentyl) Triphenylphosphonium cation ( 18 F-FPTP) carrying the TPP moiety has been used as a mitochondrial voltage sensor for myocardial imaging by positron emission tomography (PET) 17. In vivo biodistribution and imaging studies showed that 18 F-FPTP could accumulate in the myocardium with rapid clearance from the liver and lung 18.…”

Fimasartan attenuates edema and systemic changes in egg albumin-induced paw inflammation in rats

“…The study was approved by the Scientific and Ethical Committees of the College of Pharmacy-University of Baghdad. After overnight fasting, twenty-four rats were grouped into four groups (n=6) and treated intraperitoneally as previously described [12]: Group I rats (positive control) received vehicle only (5 ml/kg) by intraperitoneal route [26], group II rats received diclofenac sodium intraperitoneally in a dose of 25 mg/kg [11,27,28], group III rats were given fimasartan intraperitoneally in a dose of 3 mg/kg [29], and group IV received fimasartan intraperitoneally in a dose of 10 mg/kg [30,31]. Another group (negative control, group V) treated with an equivalent volume of vehicle as in the positive control group (5 ml/kg) intraperitoneally was also used for the TNF-α and IL-6 assay [9].…”

The Ameliorative Effect of Fimasartan against Methotrexate-Induced Nephrotoxicity in Rats

“…Group Ⅲ (FMS group): Rats received a daily IP injection of fimasartan (3 mg/kg/day) for 7 successive days. A solution of (0.05% w/v) FMS was prepared by dissolving fimasartan potassium trihydrate in water on the day of administration (18,23,24) . Group Ⅳ (α-Toc group): Rats received αtocopherol (1 g/kg/day) orally for 7 successive days (14) .…”