Bush sophora root polysaccharide could help prevent aflatoxin B1-induced hepatotoxicity in the primary chicken hepatocytes

Bush sophora root polysaccharide could help prevent aflatoxin B1-induced hepatotoxicity in the primary chicken hepatocytes
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槐根多糖有助于预防黄曲霉毒素B1引起的鸡原代肝细胞的肝毒性。

DOI:
10.1016/j.toxicon.2018.05.019
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发表时间:
2018-08-01
期刊:
影响因子:
2.8
通讯作者:
Huang, Kehe
Huang, Kehe
中科院分区:
医学4区
文献类型:
--
作者:
Gan, Fang;Yang, Yulan;Huang, Kehe

文献摘要

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本研究旨在观察苦参多糖(BSRPS)对黄曲霉毒素B1(AFB 1)肝毒性的影响,并探讨其作用机制。本实验以原代鸡肝细胞为模型。结果表明,黄曲霉毒素B_1对鸡肝细胞有明显的毒性作用,表现为细胞活力降低,LDH活性、ALT和AST水平升高。与空白对照组相比,0.16 μ M的黄曲霉毒素B1可显著增加肝细胞色素P450 1A 5(CYP 450 1A 5)mRNA和丙二醛(MDA)含量,降低肝细胞锰超氧化物歧化酶(SOD 2)活性和mRNA水平,降低谷胱甘肽过氧化物酶(GSH-Px)活性。BSRPS在8.93 μ M、17.86 μ M和35.72 μ M的浓度下可显著逆转AFB 1诱导的上述变化,其中17.86 μ M的BSRPS对AFB 1诱导的肝细胞损伤的保护作用最大。SOD 2特异性siRNA敲低SOD 2后,BSRPS对AFB 1诱导的CYP 450 IA 5 mRNA水平升高和肝毒性的保护作用明显减弱。以上结果提示,BSRPS可能通过上调SOD 2表达,下调CYP 450 1A 5 mRNA水平,对AFB 1诱导的原代鸡肝细胞毒性具有保护作用。
The aim of this study was to evaluate the effects of bush sophora root polysaccharide (BSRPS) on the aflatoxin B1 (AFB1)-induced hepatotoxicity and to explore the underlying mechanisms. The primary chicken hepatocytes were used as the model in the present experiment. The results showed that AFB1 induced hepatotoxicity of chicken hepatocytes in a dose dependent manner as demonstrated by decreasing cell viability and increasing LDH activity, ALT and AST levels. AFB1 at 0.16 mu M significantly increased the levels of hepatic cytochrome P450 1A5 (CYP450 1A5) mRNA and malondialdehyde (MDA) and decreased the activity and mRNA level of manganese superoxide dismutase(SOD2) and the glutathione peroxidases (GSH-Px) activity in the hepatocytes compared with the blank control. BSRPS at 8.93 mu M, 17.86 mu M, and 35.72 mu M supplementation could significantly reverse the above-mentioned changes induced by AFB1, and 17.86 mu M of BSRPS has the largest effects on protecting the AFB1-induced hepatocytes damage. Knock-down of SOD2 by SOD2-specific siRNA significantly eliminated the protective effects of BSRPS on AFB1-induced the increase of CYP450 IA5 mRNA levels and hepatotoxicity. These results suggested that the BSRPS has protective effects on AFB1-induced hepatotoxicity by down-regulating CYP450 1A5 mRNA level via up-regulating SOD2 expression in the primary chicken hepatocytes.