Anti-oxidative and anti-inflammatory benefits of the ribonucleoside analogue 5-azacitidine in mice with acetaminophen-induced toxic hepatitis

• Published in: International immunopharmacology Vol. 48; pp. 91 - 95
• Main Authors: Yang, Changming, Yi, Jun, Gong, Xianqiong, Ge, Pu, Dai, Jie, Lin, Ling, Xing, Yu, Zhang, Li
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2017; Elsevier BV
• Subjects: 5-Azacitidine; Abnormalities; Acetaminophen; Acute myeloid leukemia; Alanine; Alanine transaminase; Analgesics; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Aspartate aminotransferase; Azacitidine - pharmacology; Azacitidine - therapeutic use; Azacytidine; Biocompatibility; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; DNA methyltransferases; Glutathione - metabolism; Hepatitis; In vivo methods and tests; Interleukin 6; Interleukin-6 - blood; Leukemia; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Malondialdehyde; Malondialdehyde - metabolism; Methylation; Mice; Mice, Inbred C57BL; Myeloid leukemia; Nitric oxide; Nitric Oxide - blood; Nitric Oxide - metabolism; Overdose; Oxidative stress; Oxidative Stress - drug effects; Peroxidase; Peroxidase - metabolism; Toxic hepatitis; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-TNF; Tumor necrosis factor-α; 5-Azacitidine; Toxic hepatitis; DNA methyltransferases; Methylation; Acetaminophen
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2017.05.001

Toxic hepatitis induced by overdose of acetaminophen (APAP) is one of the major life-threatening problems, oxidative stress and inflammatory injury are the essential underlying mechanisms. 5-Azacytidine (5-AZA) is a ribonucleoside analogue which has been approved for the treatment of patients with acute myeloid leukemia and myelodyplastic syndrome, but recent studies also found that 5-AZA might have anti-oxidative and anti-inflammatory benefits in non-tumor disorders. In the present study, the potential effects of 5-AZA on APAP-induced toxic hepatitis were investigated in a mouse model in vivo. The results indicated that treatment with 5-AZA suppressed the elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma, alleviated APAP-induced histological abnormalities in liver, improved the survival rate of the experimental animals. These effects were associated with restored level of GSH and suppressed elevation of malondialdehyde (MDA) in liver. In addition, treatment with 5-AZA suppressed APAP-induced production of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and nitric oxide (NO), 5-AZA also reversed the upregulation of myeloperoxidase (MPO) in the liver of APAP-exposed mice. The above data indicated that 5-AZA could provide beneficial effects in APAP-induce toxic hepatitis, these effects might attribute to its anti-oxidative and anti-inflammatory actions.
•5-AZA attenuated APAP-induced hepatic lesions and aminotransferases release.•5-AZA alleviated APAP-induced oxidative stress in liver.•5-AZA suppressed APAP-induced inflammatory response.•5-AZA improved the survival rate of APAP-exposed mice.