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膳食姜黄素的双重作用:通过调节参与黄曲霉毒素生物活化和解毒的肝脏I相和II相酶,减轻黄曲霉毒素诱导的氧化应激和肝损伤。

Dual Role of Dietary Curcumin Through Attenuating AFB-Induced Oxidative Stress and Liver Injury via Modulating Liver Phase-I and Phase-II Enzymes Involved in AFB Bioactivation and Detoxification.

作者信息

Muhammad Ishfaq, Wang He, Sun Xiaoqi, Wang Xinghe, Han Meiyu, Lu Ziyin, Cheng Ping, Hussain Muhammad A, Zhang Xiuying

机构信息

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Laboratory of Veterinary Pathology, Faculty of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.

出版信息

Front Pharmacol. 2018 May 25;9:554. doi: 10.3389/fphar.2018.00554. eCollection 2018.

Abstract

It is well understood that liver cytochrome p450 enzymes are responsible for AFB bioactivation, while phase-II enzymes regulated by the transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) are involved in detoxification of AFB. In this study, we explored the potential of curcumin to prevent AFB-induced liver injury by modulating liver phase-I and phase-II enzymes along with Nrf2 involved in AFB bioactivation and detoxification. Arbor Acres broiler were divided into four groups including control group (G1; fed only basal feed), curcumin alone-treated group (G2; 450 mg/kg feed), AFB-fed group (G3; 5 mg/kg feed), and curcumin plus AFB group (G4; 5 mg AFB+450 mg curcumin/kg feed). After 28 days, liver and blood samples were collected for different analyses. Histological and phenotypic results revealed that AFB-induced liver injury was partially ameliorated by curcumin supplementation. Compared to AFB alone-treated group, serum biochemical parameters and liver antioxidant status showed that curcumin supplementation significantly prevented AFB-induced liver injury. RT-PCR and western blot results revealed that curcumin inhibited CYP enzymes-mediated bioactivation of AFB at mRNA and protein level. Transcription factor Nrf2, its downstream genes such as GSTA3, and GSTM2 mRNA, and protein expression level significantly upregulated via dietary curcumin. In addition, GSTs enzyme activity was enhanced with dietary curcumin which plays a crucial role in AFB-detoxification. Conclusively, the study provided a scientific basis for the use of curcumin in broiler's diet and contributed to explore the multi-target preventive actions of curcumin against AFB-induced liver injury through the modulation of phase-I and phase-II enzymes, and its potent anti-oxidative effects.

摘要

众所周知,肝脏细胞色素P450酶负责黄曲霉毒素B(AFB)的生物活化,而由转录因子核因子红系2相关因子2(Nrf2)调节的II相酶参与AFB的解毒过程。在本研究中,我们探讨了姜黄素通过调节参与AFB生物活化和解毒的肝脏I相和II相酶以及Nrf2来预防AFB诱导的肝损伤的潜力。艾拔益加肉鸡被分为四组,包括对照组(G1;仅饲喂基础饲料)、单独姜黄素处理组(G2;450毫克/千克饲料)、AFB饲喂组(G3;5毫克/千克饲料)和姜黄素加AFB组(G4;5毫克AFB + 450毫克姜黄素/千克饲料)。28天后,采集肝脏和血液样本进行不同分析。组织学和表型结果显示,补充姜黄素可部分改善AFB诱导的肝损伤。与单独AFB处理组相比,血清生化参数和肝脏抗氧化状态表明,补充姜黄素可显著预防AFB诱导的肝损伤。逆转录聚合酶链反应(RT-PCR)和蛋白质印迹结果显示,姜黄素在mRNA和蛋白质水平上抑制CYP酶介导的AFB生物活化。转录因子Nrf2、其下游基因如谷胱甘肽S-转移酶A3(GSTA3)和谷胱甘肽S-转移酶M2(GSTM2)的mRNA和蛋白质表达水平通过日粮姜黄素显著上调。此外,日粮姜黄素增强了谷胱甘肽S-转移酶(GSTs)的酶活性,其在AFB解毒中起关键作用。总之,该研究为姜黄素在肉鸡日粮中的应用提供了科学依据,并有助于探索姜黄素通过调节I相和II相酶及其强大的抗氧化作用对AFB诱导的肝损伤的多靶点预防作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bf2/5981209/5d211a87bdfb/fphar-09-00554-g001.jpg

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