Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats.
Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats.
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DOI：
10.1155/2016/1972793
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发表时间：
2016
影响因子：
--
通讯作者：
Trigun SK
中科院分区：
文献类型：
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作者：
Maurya BK;Trigun SK
已知的抗氧化剂非瑟酮已被发现对某些细胞系具有细胞毒性。然而，其抑制体内肿瘤生长的机制仍未探索。最近，我们发现黄曲霉毒素B1（AFB 1）诱导的大鼠肝癌发生与氧化应激-炎症通路的激活有关。本文描述了20 mg/kg b.w.非瑟酮对两种剂量1 mg/kg b.w.诱导的肝细胞癌（HCC）中抗氧化酶维斯氧化应激水平以及某些促炎细胞因子的影响。大鼠腹腔注射AFB 1。由于非瑟酮治疗，观察到大多数抗氧化酶的水平降低，与HCC肝脏中活性氧水平升高一致，恢复其正常分布。此外，非瑟酮治疗可以使TNFα和IL 1 α的表达正常化，这两种促炎细胞因子被报道参与HCC发病机制。这些观察结果与非瑟酮治疗的HCC大鼠肝脏中肿瘤病变的消退和降低的GST-π（胎盘型谷胱甘肽-S-转移酶）水平（HCC标志物）一致。结果表明，非瑟酮减弱黄曲霉毒素B1诱导的肝癌的氧化应激-炎症通路。
Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1) induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC) induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase) level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis.