Febuxostat Modulates MAPKNF-κBp65TNF-α Signaling in Cardiac Ischemia-Reperfusion Injury
Joint Authors
Bhatia, Jagriti
Ojha, Shreesh
Malhotra, Rajiv Kumar
Khan, Sana Irfan
Rani, Neha
Sahu, Anil Kumar
Tomar, Ameesha
Garg, Shanky
Nag, Tapas Chandra
Ray, Ruma
Arya, Dharmveer S.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-08-24
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Xanthine oxidase and xanthine dehydrogenase have been implicated in producing myocardial damage following reperfusion of an occluded coronary artery.
We investigated and compared the effect of febuxostat and allopurinol in an experimental model of ischemia-reperfusion (IR) injury with a focus on the signaling pathways involved.
Male Wistar rats were orally administered vehicle (CMC) once daily (sham and IR + control), febuxostat (10 mg/kg/day; FEB10 + IR), or allopurinol (100 mg/kg/day; ALL100 + IR) for 14 days.
On the 15th day, the IR-control and treatment groups were subjected to one-stage left anterior descending (LAD) coronary artery ligation for 45 minutes followed by a 60-minute reperfusion.
Febuxostat and allopurinol pretreatment significantly improved cardiac function and maintained morphological alterations.
They also attenuated oxidative stress and apoptosis by suppressing the expression of proapoptotic proteins (Bax and caspase-3), reducing TUNEL-positive cells, and increasing the level of antiapoptotic proteins (Bcl-2).
The MAPK-based molecular mechanism revealed suppression of active JNK and p38 proteins concomitant with the rise in ERK1/ERK2, a prosurvival kinase.
Additionally, a reduction in the level of inflammatory markers (TNF-α, IL-6, and NF-κB) was also observed.
The changes observed with febuxostat were remarkable in comparison with those observed with allopurinol.
Febuxostat protects relatively better against IR injury than allopurinol by suppressing inflammation and apoptosis mediating the MAPK/NF-κBp65/TNF-α pathway.
American Psychological Association (APA)
Khan, Sana Irfan& Malhotra, Rajiv Kumar& Rani, Neha& Sahu, Anil Kumar& Tomar, Ameesha& Garg, Shanky…[et al.]. 2017. Febuxostat Modulates MAPKNF-κBp65TNF-α Signaling in Cardiac Ischemia-Reperfusion Injury. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-13.
https://search.emarefa.net/detail/BIM-1195927
Modern Language Association (MLA)
Khan, Sana Irfan…[et al.]. Febuxostat Modulates MAPKNF-κBp65TNF-α Signaling in Cardiac Ischemia-Reperfusion Injury. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-13.
https://search.emarefa.net/detail/BIM-1195927
American Medical Association (AMA)
Khan, Sana Irfan& Malhotra, Rajiv Kumar& Rani, Neha& Sahu, Anil Kumar& Tomar, Ameesha& Garg, Shanky…[et al.]. Febuxostat Modulates MAPKNF-κBp65TNF-α Signaling in Cardiac Ischemia-Reperfusion Injury. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-13.
https://search.emarefa.net/detail/BIM-1195927
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195927