Effect of febuxostat on biochemical parameters of hyperlipidemia induced by a high-fat diet in rabbits

• Published in: Canadian journal of physiology and pharmacology 2019-07, Vol.97 (7), p.611-622
• Main Authors: Heikal, Mohammed M, Shaaban, Ahmed A, Elkashef, Wagdi F, Ibrahim, Tarek M
• Format: Article
• Language: English
• Subjects: Antioxidants; Biochemistry; Carboxymethylcellulose; Cellulose; Cholesterol; Cytokines; Diet; dérivés réactifs de l’oxygène; Effects; Enzymatic activity; febuxostat; fébuxostat; High fat diet; Hyperlipidemia; hyperlipidémie; Inflammation; Inhibitor drugs; Iron compounds; Lipid peroxidation; Low density lipoproteins; Oxidases; Oxidative stress; Peroxidation; Pharmacology; Physiology; Rabbits; Reactive oxygen species; Serum levels; stress oxydatif; Studies; TNF-α; Xanthine oxidase
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2018-0731

Febuxostat, a highly potent xanthine oxidase inhibitor with an antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. The aim of this study was to test the potential antioxidant and anti-inflammatory effects of febuxostat and (or) stopping a high-fat diet on the biochemical parameters in rabbits with hyperlipidemia induced by a high-fat diet. Male New Zealand rabbits were distributed into 3 groups: a normal control group fed standard chow for 12 weeks and 2 other groups fed a high-fat diet with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks, one high-fat diet group received 0.5% carboxymethyl cellulose, whereas the other group was treated with febuxostat (2 mg/kg per day p.o.). Febuxostat significantly lowered low-density lipoprotein cholesterol (“bad” cholesterol) compared to the untreated group (high-fat diet group). Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, proinflammatory cytokines, and enhancing antioxidant enzyme activity. Stopping the hyperlipidemic diet in the high-fat diet group did not show improvement. These findings indicate the antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping a hyperlipidemic diet without treatment is not sufficient once injury has occurred.