Febuxostat ameliorates doxorubicin-induced cardiotoxicity in rats

Krishnamurthy, Bhaskar; Rani, Neha; Bharti, Sudhakar; Golechha, Mahaveer; Bhatia, Jagriti; Nag, Tapas Chandra; Ray, Ruma; Arava, Sudheer; Arya, Dharamvir Singh

doi:10.1016/j.cbi.2015.05.013

Cited by 42 publications

(28 citation statements)

References 29 publications

(33 reference statements)

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“…Thus, SUA in DM + Fx group was still significantly higher than that in both NC and NC + Fx groups. According to previous studies, Fx at 5 mg/kg is a moderate dose for rats and mice [32]; however, we did not observe complete normalization of SUA when compared to that in few other studies involving SUA [33]. One reason for this might result from the relatively short-term intervention of Fx (only 8 weeks).…”

Section: Discussioncontrasting

confidence: 82%

Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in Streptozotocin-Induced Diabetic Rats

Ran

et al. 2017

International Journal of Nephrology

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Aim. In this study, we aimed to investigate the effects of febuxostat, a novel inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-) induced diabetic rats. Methods. Diabetes was induced by the intraperitoneal injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as controls. The control and diabetic rats were treated with and without febuxostat for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected every 4 weeks. Rat livers were extracted for detecting gene expression, content, and bioactivity of XO. Results. Diabetic rats showed significantly increased serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels. Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were also significantly increased in these rats. In diabetic rats, at week 8, febuxostat decreased SUA by 18.9%, while UAA was increased by 52.0%. However, UCr and urinary urea nitrogen (UUN) levels remained unchanged, while SCr and BUN levels decreased by >30% in these rats. Although hepatic gene expression, content, and activity of XO increased significantly in diabetic rats, febuxostat only slightly decreased its content. Conclusions. Febuxostat significantly attenuated renal damage in STZ-induced diabetic rats in addition to exerting hypouricemic effect.

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Section: Discussioncontrasting

confidence: 82%

Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in Streptozotocin-Induced Diabetic Rats

Ran

et al. 2017

International Journal of Nephrology

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“…Elevated ROS may induce apoptotic cell death and damage to tissues and organs (40)(41)(42). NF-κBp65 is predominant in the apoptotic regulation process by regulating the expression of downstream Bcl-2 genes.…”

Section: Discussionmentioning

confidence: 99%

Magnesium isoglycyrrhizinate ameliorates doxorubicin‑induced acute cardiac and hepatic toxicity via anti‑oxidant and anti‑apoptotic mechanisms in mice

Zhang

Song

et al. 2017

Exp Ther Med

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Abstract. The present study investigated the effects and potential mechanisms of action of magnesium isoglycyrrhizinate (MgIG) in doxorubicin (DOX)-treated mice. Histopathological analysis and western blot analysis were conducted in the liver and heart tissues and biochemical analysis of the serum was performed. The results revealed that MgIG (10, 20 and 40 mg/kg/day) could protect the structure and functions of the liver and heart by inhibiting the activities of the myocardial enzymes creatine kinase (CK), CK-MB and lactate dehydrogenase and the hepatic-specific enzymes aspirate aminotransferase and alanine aminotransferase, increasing the activities of the antioxidants superoxide dismutase and glutathione peroxidase, and inhibiting cellular apoptosis induced by DOX (30 mg/kg). These results demonstrate that inhibiting lipid peroxidation and reducing myocardial and hepatocyte apoptosis may be one of the mechanisms by which MgIG exhibits hepatoprotective and cardioprotective effects in DOX-treated mice.

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“…Hence, febuxostat decreases the production of uric acid [8]. Krishnamurthy et al study demonstrated a significant effect of febuxostat on attenuation of DIC through reduction of cardiac injury biomarkers and activation of endogenous antioxidant capacity as febuxostat improves diastolic pressure with significant positive inotropic and lusitropic effects [9]. These findings give a clue that febuxostat could produce a cardioprotective due to its antioxidant effect.…”

Section: Introductionmentioning

confidence: 96%

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

Al-Kuraishy

Al-Gareeb

Al-Hussaniy³

2019

Asian J Pharm Clin Res

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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.

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Febuxostat ameliorates doxorubicin-induced cardiotoxicity in rats

Cited by 42 publications

References 29 publications

Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in Streptozotocin-Induced Diabetic Rats

Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in Streptozotocin-Induced Diabetic Rats

Magnesium isoglycyrrhizinate ameliorates doxorubicin‑induced acute cardiac and hepatic toxicity via anti‑oxidant and anti‑apoptotic mechanisms in mice

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

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