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PO1-2-42

Febuxostat remediates doxorubicin-induced cardiomyopathy

[Speaker] Anil Kumar Sahu:1
[Co-author] Dharamvir Arya:1, Jagriti Bhatia:1, Bhaskar Krishnamurthy:1
1:Pharmacology, All India Institute of Medical Sciences, India

Background:
Xanthine oxidase inhibitors have found to play a role in oxidative damage. Doxorubicin induces dilated cardiomyopathy via oxidative damage. Thus we hypothesize that febuxostat helps in remediation of doxorubicin-induced cardiomyopathy.
Methods:
For 14 days male Albino Wistar rats, doxorubicin with febuxostat (10mg/kg/day oral), doxorubicin with carvedilol (30mg/kg/day oral), doxorubicin (2.5mg/kg/day for 6 total doses on alternate days) and control (normal saline 2.5ml/kg/day i.p. for 6 total doses on alternate days) was administered in the above four respective groups.
Results:
In the doxorubicin with febuxostat group, biochemical, hemodynamic and histological markers evidentially had a protective role in doxorubicin-induced cardiomyopathy. Febuxostat decreased caspase-3 and Bax, increased Bcl-2 and was TUNEL positive. Creatine kinase- MB (CKMB) and brain natriuretic peptide (BNP) levels reduced in the group treated with Febuxostat.
Conclusion:
Febuxostat prevents oxidative stress and defends cardiac myocytes against doxorubicin-induced cardiomyopathy.

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