Open AccessFEBUXOSTAT MODULATES OXIDATIVE AND APOPTOTIC PATHWAYS IN ACUTE DOXORUBICIN‑INDUCED CARDIOTOXICITY: AN EXPERIMENTAL ANIMAL MODEL STUDY
Author(s) -
Hayder M Al-Kuraishy,
Ali I. AlGareeb,
Hany Akeel Al-Hussaniy
Publication year - 2019
Publication title -
asian journal of pharmaceutical and clinical research
Language(s) - English
Resource type - Journals
eISSN - 2455-3891
pISSN - 0974-2441
DOI - 10.22159/ajpcr.2019.v12i4.31162
Subject(s) - febuxostat , pharmacology , cardiotoxicity , glutathione peroxidase , xanthine oxidase , doxorubicin , malondialdehyde , oxidative stress , medicine , uric acid , chemistry , hyperuricemia , toxicity , biochemistry , superoxide dismutase , chemotherapy , enzyme
Objectives: Doxorubicin is one of the most important and powerful anticancer drugs, the most pronounced limitation for its use is toxicity on normal cells. Mechanism of doxorubicin-induced cardiotoxicity (DIC) is multifactorial and complex, including direct DNA damage, formation of free radicals, interference with DNA repair, and activation of immune reactions. Febuxostat is a non-purine-selective xanthine oxidase inhibitor decrease the production of uric acid. The aim of the present study was to evaluate the influence of febuxostat on doxorubicin-induced acute cardiotoxicity in rats regarding oxidative stress and antiapoptotic effects.
Methods: A total of 30 Sprague Dawley male rats were used which subdivided into three groups: Group I (negative control group) received normal saline for 10 days, Group II (positive control group) received normal saline plus single dose of doxorubicin (15 mg/kg, IP), and Group III (treated group) received febuxostat (10 mg/kg, po), for 10 successive days plus single dose of doxorubicin (15 mg/kg, I.P.). Serum brain natriuretic peptide (BNP), cardiac troponin I (cTn-I), caspase-3, glutathione peroxidase (GSH-Px), lipid peroxidase (LPO), malondialdehyde (MDA), and tumor necrosis factor alpha were estimated by ELISA kit method.
Results: Febuxostat administration before doxorubicin led to significant decrease on cardiac troponin, caspase-3, and elevation in GSH-Px levels significantly p 0.05 compare to doxorubicin.
Conclusion: Febuxostat attenuates DIC through modulation of antioxidant, anti-inflammatory, and antiapoptotic biomarkers.