Effects of febuxostat and inosine on rat myocardial ischemia/reperfusion injury
نویسندگان
چکیده
Adenosine triphosphate (ATP) is the source of energy for various organs especially the heart muscle. ATP degradation pathways reach to uric acid through hypoxanthine and xanthine as the last two steps, which are catalyzed by xanthine oxidase (XO). Treatment with XO inhibitor has been shown to increase myocardial mechanical efficiency and improves cardiac contractility and myocardial ischemia. The purpose of this study is to investigate whether treatment with an XO inhibitor febuxostat along with a nucleoside inosine, upstream of hypoxanthine, can have protective effects on rat myocardial ischemia/reperfusion injury. Treatment with both febuxostat alone and (febuxostat plus inosine) significantly reduced the infarct size (23.24 ± 1.89% and 22.34 ± 2.28%, respectively; n=5 each) as compared with the control treatment (34.40 ± 2.97%, n=5, *P<0.0174 and **P<0.0109, respectively). However, there was no significant difference between febuxostat-treated and (febuxostat plus inosine)-treated groups. Because XO enzyme activities in rodents were reported to be 100 times higher than those in humans, XO inhibition alone may supply enough materials for ATP production in rodents. We think there is a possibility that combination therapy with febuxostat plus inosine will be more effective than febuxostat alone in reducing the myocardial ischemia/reperfusion injury in humans, and further clinical investigation is needed to verify this. Correspondence to: Yoshinori Seko, M.D., Ph.D., Department of Biofunctional Microbiota, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan, Tel: +81-3-5802-1591; Fax: +81-3-3813-5512; E-mail: [email protected]
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