Febuxostat Modulates Oxidative and Apoptotic Pathways in Acute Doxorubicin‑induced Cardiotoxicity: An Experimental Animal Model Study

Abstract

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. While the effects of febuxostat on BNP, LPO, MDA, tumor necrosis-alpha were insignificant p>0.05 compare to doxorubicin.
 Conclusion: Febuxostat attenuates DIC through modulation of antioxidant, anti-inflammatory, and antiapoptotic biomarkers.

The Use of Panax Ginseng to Reduce the Cardiotoxicity of Doxorubicin and Study its Effect on Modulating Oxidative Stress, Inflammatory, and Apoptosis Pathways

“…First, Panax ginseng reduces cardiac troponin and brain natriuretic peptide during doxorubicin-induced cardiotoxicity and has a protective effect. This modulation of cardiac troponin reinforces the research of Jang et al [12], [19].…”

“…The effect of Panax ginseng on caspase-3 levels is due to the inhibition of pro-apoptotic protein, which induces the expression of the pro-apoptotic level of caspase-3. Therefore, Panax ginseng attenuates apoptosis by modulating the intrinsic pathway [19], [23]. Moreover, a study found that an increase in caspase-3 is related to Panax ginseng's anticancer effect since ginsenoside inhibits cell growth through a caspase-3-mediated apoptosis mechanism [19].…”

Leptin hormone and its effectiveness in reproduction, metabolism, immunity, diabetes, hopes and ambitions

“…In addition, leptin may play an important role in the relationship between obesity and colorectal cancer [ 29 ]. Recently, several studies have been conducted to study the efficacy of leptin with some anticancer drugs such as doxorubicin [ 30 ], which treat a wide range of cancers [ 31 ].…”

Combination of Panax ginseng C. A. Mey and Febuxostat Boasted Cardioprotective Effects Against Doxorubicin-Induced Acute Cardiotoxicity in Rats

“…In the present study, febuxostat showed a reasonable but non-significant decrease in BNP serum levels, as shown previously ( Ahmed et al, 2021 ). This was due to the antioxidant, anti-inflammatory, and anti-apoptotic effects of febuxostat ( Al-Kuraishy et al, 2019 ). Furthermore, DOX may induce myocardial cell apoptosis by activating mitochondrial caspase-3 ( Fidale et al, 2018 ).…”

“…Our observations demonstrated that febuxostat could limit the infarct size of acute myocardial infarction. This reduction is accompanied by changes in the level of matrix metalloproteinase enzymes, biomarkers of cardiac cell injury ( Al-Kuraishy et al, 2019 ).…”