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

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-alpha), 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.