Arctigenin Attenuates Ischemia/Reperfusion Induced Ventricular Arrhythmias by Decreasing Oxidative Stress in Rats.

Abstract

BACKGROUND/AIMS:

Arctigenin (ATG) has been shown to possess anti-inflammatory, immunemodulatory, anti-viral, anti-microbial, anti-carcinogenic, vasodilatory and anti-platelet aggregation properties. However, the protective role of ATG in prevention of arrhythmias induced by myocardial ischemia/reperfusion is unknown. The aim of this study was to investigate the anti-arrhythmia effect of ATG in an ischemia/reperfusion injured rat heart model and explore the related mechanisms.

METHODS:

Rats were randomly exposed to sham operation, myocardial ischemia/ reperfusion (MI/R) alone, ATG+ MI/R, pretreated with ATG in low (12.5 mg/kg/day), medium (50 mg/kg/day) and high dose (200 mg/kg/day), respectively. Ventricular arrhythmias were assessed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) in myocardial tissue were determined by chemical analysis.

RESULTS:

Compared to MI/R, rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/day showed significantly reduced incidence and duration of ventricular fibrillation, ventricular tachycardia and ventricular ectopic beat (VEB), and decreased the arrhythmia score during the 30-min ischemia. Incidence and duration of ventricular tachycardia, infarction size and arrhythmia scores in these groups were significantly decreased during the 120-min reperfusion. No ventricular fibrillation occurred during the period of reperfusion. Rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/ day markedly enhanced the activities of antioxidant enzymes SOD and GSH-Px, reduced the level of MDA. No differences were observed between the group pretreated with a low dose of ATG and the sham group. Administration of ATG significantly increased the expression of antioxidant stress protein Nrf2, Trx1 and Nox1.

CONCLUSION:

Our data suggested that ATG plays anti-arrhythmia role in ischemia/reperfusion injury, which is probably associated with attenuating oxidative stress by Nrf2 signaling pathway.

• Authors: Jing Yang, Hong-Shan Yin, Ya-Jing Cao, Zhi-An Jiang, Yong-Jun Li, Mu-Chun Song, Yong-Fei Wang, Zhi-Hua Wang, Rong Yang, Yun-Fa Jiang, Jin-Peng Sun, Bo-Yi Liu, Chuan Wang
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 49 Issue 2 Pg. 728-742 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 30165360 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Furans
• Lignans
• NF-E2-Related Factor 2
• Txn1 protein, rat
• Malondialdehyde
• Thioredoxins
• Glutathione Peroxidase
• Superoxide Dismutase
• NADPH Oxidase 1
• NOX1 protein, rat
• arctigenin

Topics

• Animals
• Arrhythmias, Cardiac (etiology, metabolism, prevention & control)
• Disease Models, Animal
• Furans (pharmacology, therapeutic use)
• Glutathione Peroxidase (metabolism)
• Lignans (pharmacology, therapeutic use)
• Male
• Malondialdehyde (metabolism)
• Myocardial Infarction (pathology)
• Myocardium (metabolism)
• NADPH Oxidase 1 (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications)
• Superoxide Dismutase (metabolism)
• Thioredoxins (metabolism)