Anti-oxidative and anti-inflammatory benefits of the ribonucleoside analogue 5-azacitidine in mice with acetaminophen-induced toxic hepatitis
Anti-oxidative and anti-inflammatory benefits of the ribonucleoside analogue 5-azacitidine in mice with acetaminophen-induced toxic hepatitis
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DOI：
10.1016/j.intimp.2017.05.001
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发表时间：
2017-07-01
影响因子：
5.6
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Yang, Changming;Yi, Jun;Zhang, Li
过量服用对乙酰氨基酚（APAP）引起的中毒性肝炎是威胁生命的主要问题之一，氧化应激和炎症损伤是其重要的潜在机制。 5-氮杂胞苷 (5-AZA) 是一种核糖核苷类似物，已被批准用于治疗急性髓系白血病和骨髓增生异常综合征患者，但最近的研究还发现，5-AZA 可能在非肿瘤疾病中具有抗氧化和抗炎作用。在本研究中，在小鼠体内模型中研究了 5-AZA 对 APAP 诱导的中毒性肝炎的潜在影响。结果表明，5-AZA治疗可抑制血浆丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的升高，减轻APAP引起的肝脏组织学异常，提高实验动物的存活率。这些作用与肝脏中 GSH 水平的恢复和丙二醛 (MDA) 升高的抑制有关。此外，5-AZA 治疗可抑制 APAP 诱导的肿瘤坏死因子-α (TNF-α)、白细胞介素 6 (IL-6) 和一氧化氮 (NO) 的产生，5-AZA 还可逆转 APAP 暴露小鼠肝脏中髓过氧化物酶 (MPO) 的上调。上述数据表明5-AZA可以对APAP诱导的中毒性肝炎产生有益作用，这些作用可能归因于其抗氧化和抗炎作用。
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.