Some histone deacetylase inhibitors protect against dextran sulphate sodium-induced hepatotoxicity in mice

Abstract

Background and Aims: Ulcerative colitis is an inflammatory bowel disease that affects many people worldwide and has extrain testinal effects. Dextran sulphate sodium(DSS)isasyntheticpolysaccharidewidelyusedtomodelulcerativecolitisinexperimental animals. Histone deacetylase (HDAC) inhibitors are molecules that cause changes in gene expression and play a role in many biological events such as inflammatory response formation, cell growth, and differentiation. The aim of this study was to reveal the effects of HDAC inhibitors such as sodium phenylbutyrate (PBA) and suramin on liver morphology, inflammatory mediators, oxidative stress, and antioxidant system in DSS-induced liver injury. Methods: In this study, 48 male C57BL/6 mice were divided into six groups: control mice; mice administered PBA (150 mg/kg/d, intraperitoneally) or suramin (25 mg/kg/d, intraperitoneally) for 7 days; mice administered 3% DSS orally for 5 days; animals treated with PBA and DSS; and mice treated with suramin and DSS. The effects of PBA and suramin on liver histology were examined microscopically; their impacts on antioxidant parameters and oxidative stress were assessed spectrophotometrically; and their influence on COX-2 and TNF-𝛼 expressions was analysed by Western blotting in liver tissues of mice administered DSS. Results: DSS application resulted in extensive necrosis, increased lipid peroxidation levels, and myeloperoxidase activity, as well as decreased GSH levels and SOD activities in liver tissues. It also increased COX-2 and TNF-𝛼 expressions in DSS-induced liver toxicity. PBA or suramin treatment prevented liver injury by mitigating the effects of DSS. Conclusion: This study showed that PBA and suramin have cytoprotective, anti-inflammatory, and antioxidant effects on DSS induced hepatotoxicity. Consequently, HDAC inhibitors such as PBA and suramin may be considered effective prophylactic and therapeutic agents against DSS-induced liver injury.

Keywords

• Histone Deacetylase Inhibitors
• Sodium Phenylbutyrate
• Suramin
• Dextran Sulphate Sodium
• Liver
• Mice

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