Fraxinellone protects against cardiac injury and decreases ventricular fibrillation susceptibility during myocardial ischemia-reperfusion

Rui Huang; Xing Zhong; Pusong Tang; Qingning Huang; Xin Chen; Lu Ye; Dan Luo; Yaqin Yang; Yuhua Lei

Biomedicine & Pharmacotherapy (Nov 2024)

Fraxinellone protects against cardiac injury and decreases ventricular fibrillation susceptibility during myocardial ischemia-reperfusion

Rui Huang,
Xing Zhong,
Pusong Tang,
Qingning Huang,
Xin Chen,
Lu Ye,
Dan Luo,
Yaqin Yang,
Yuhua Lei

Affiliations

Rui Huang: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Provincial Key Lab of Selenium Resources and Bio Applications, Enshi, Hubei Province, China
Xing Zhong: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Minzu University, Enshi, Hubei Province, China
Pusong Tang: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Minzu University, Enshi, Hubei Province, China
Qingning Huang: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Provincial Key Lab of Selenium Resources and Bio Applications, Enshi, Hubei Province, China
Xin Chen: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Provincial Key Lab of Selenium Resources and Bio Applications, Enshi, Hubei Province, China
Lu Ye: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Minzu University, Enshi, Hubei Province, China
Dan Luo: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Provincial Key Lab of Selenium Resources and Bio Applications, Enshi, Hubei Province, China
Yaqin Yang: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Provincial Key Lab of Selenium Resources and Bio Applications, Enshi, Hubei Province, China; Corresponding authors at: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China.
Yuhua Lei: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China; Hubei Provincial Key Lab of Selenium Resources and Bio Applications, Enshi, Hubei Province, China; Corresponding authors at: Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei Province, China.

Journal volume & issue: Vol. 180
p. 117560

Abstract

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Background: Acute myocardial ischemia/reperfusion injury (MIRI) with complicated mechanisms contributes to a high risk of ventricular arrhythmia, high lethality, and even sudden death. In vitro, Fraxinellone (FRA) exhibits an array of biologic activities and may possess cardioprotective effects. However, no relevant studies have examined FRA's protective potential against MIRI and related ventricular arrhythmias. The present study was undertaken to determine the effectiveness of FRA on MIRI and ventricular fibrillation (VF) susceptibility in rats and to elucidate the underlying mechanisms. Methods: 48 healthy male Sprague-Dawley (SD) rats were randomly divided into the following four groups: Sham+vehicle(n=12), Sham+FRA(n=12), I/R+vehicle(n=12) and I/R+FRA(n=12). Histopathology, electrophysiological examination, HRV analysis in combination with molecular biology were used to investigate the therapeutic benefits of FRA on cardiac injury and VF susceptibility during myocardial IR. Finally, the potential mechanism by which FRA protects myocardium from MIRI was explored. Results: Pretreatment with FRA ameliorated myocardial fibrosis after MIRI in vivo, alleviated myocardial injury, inflammation, oxidative stress and apoptosis in vivo and in vitro, thereby protecting myocardium from MIRI injury. In addition, FRA administration could improve HRV, prolong ventricular effective refractory period (ERP) and action potential duration (APD), attenuate VF induction rate, and contribute to improving ventricular sympathetic nerve remodeling and ion channel remodeling. Mechanistically, FRA may reduce MIRI via the PI3K/AKT pathway. Conclusion: FRA may exert cardioprotective effects during MIRI by inhibiting myocardial inflammation, oxidative stress and apoptosis, and decrease VF susceptibility by improving sympathetic remodeling and ion channel remodeling, which might represent a potential therapeutic strategy for attenuation of MIRI.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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