Protective Effects of Topiroxostat on an Ischemia-Reperfusion Model of Rat Hearts

Circulation Journal : Official Journal of the Japanese Circulation Society
Shogo TannoIchiro Hisatome

Abstract

Ischemia/reperfusion (I/R) injury triggers cardiac dysfunctions via creating reactive oxygen species (ROS). Because xanthine oxidase (XO) is one of the major enzymes that generate ROS, inhibition of XO is expected to suppress ROS-induced I/R injury. However, it remains unclear whether XO inhibition really yields cardioprotection during I/R. The protective effects of the XO inhibitors, topiroxostat and allopurinol, on cardiac I/R injury were evaluated.Methods and Results:Using isolated rat hearts, ventricular functions, occurrence of arrhythmias, XO activities and thiobarbituric acid reactive substances (TBARS) productions and myocardial levels of adenine nucleotides before and after I/R, and cardiomyocyte death markers during reperfusion, were evaluated. Topiroxostat prevented left ventricular dysfunctions and facilitated recovery from arrhythmias during I/R. Allopurinol and the antioxidant, N-acetylcysteine (NAC), exhibited similar effects at higher concentrations. Topiroxostat inhibited myocardial XO activities and TBARS productions after I/R. I/R decreased myocardial levels of ATP, ADP and AMP, but increased that of xanthine. While topiroxostat, allopurinol or NAC did not change myocardial levels of ATP, ADP or AMP after I/R...Continue Reading

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Citations

Sep 27, 2019·The Journal of Clinical Hypertension·Shingo HigaKazuomi Kario
Aug 28, 2020·Molecular and Cellular Biochemistry·Muhammad Afzal
Jan 17, 2020·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hiroyuki MinatoYoshimi Inagaki
Jun 27, 2020·Zeitschrift Für Naturforschung. C, a Journal of Biosciences·Haiying FuMayu Huang
Jan 21, 2021·Free Radical Biology & Medicine·Yoshiro TanakaMichihiro Yoshimura
Jul 14, 2021·Diabetes & Metabolic Syndrome·Shingo Watanabe, Michio Usui

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