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Curcumin confers hepatoprotection against AFB1-induced toxicity via activating autophagy and ameliorating inflammation involving Nrf2/HO-1 signaling pathway

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Abstract

The current study demonstrated curcumin intervention against AFB1-indeuced hepatotoxicity. The hallmarks of autophagy and inflammation were assessed by transmission electron microscopy, RT-PCR and western blot. Besides, normal cellular morphology, autophagosomes were found in control and curcumin control group. In contrast, fragmented and swollen mitochondria, irregular shaped nuclei and fat droplets were visible but autophagosomes disappear in AFB1-treated group. The mRNA and protein expression levels of autophagy-related genes indicated that AFB1 significantly inhibited autophagy and induced inflammation. In addition, Nrf2 and HO-1 mRNA and protein level was significantly (p < 0.05) reduced in AFB1-fed group. Intriguingly, dietary curcumin supplementation modulated autophagy through the activation of beclin-1, ATG5, Dynein, LC3a, LC3b-I/II and downregulation of p53 & mTOR expression level. Curcumin significantly ameliorated AFB1-induced inflammation. Moreover, curcumin treatment significantly (p < 0.05) elevated AFB1-induced decrease in Nrf2 and HO-1 mRNA and protein expression level. In summary, curcumin activated autophagy and ameliorated inflammation involving Nrf2 signaling pathway which may become a new targeted therapy to prevent AFB1-induced hepatotoxicity.

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Acknowledgements

We thank the National Natural Science Foundation of China (Registration Number: 31172369) and the Natural Science Foundation of Heilongjiang Province (Registration Number: ZD201405) for providing financial funding.

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Author notes

  1. Ishfaq Muhammad and Xinghe Wang have contributed equally to this work.

Authors and Affiliations

  1. Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, 150030, Heilongjiang, People’s Republic of China

    Ishfaq Muhammad, Sihong Li, Rui Li & Xiuying Zhang

  2. Laboratory of Veterinary Pathology, Faculty of Basic Veterinary Science, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, People’s Republic of China

    Xinghe Wang

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  1. Ishfaq Muhammad
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Correspondence to Xiuying Zhang.

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All the experimental protocols were approved by Harbin Veterinary Research Institute Animal Ethics Committee (No. SYXK (Hei) 2012-2067) working under the guidelines and supervision of Chinese Academy of Agricultural Sciences (China).

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Muhammad, I., Wang, X., Li, S. et al. Curcumin confers hepatoprotection against AFB1-induced toxicity via activating autophagy and ameliorating inflammation involving Nrf2/HO-1 signaling pathway. Mol Biol Rep 45, 1775–1785 (2018). https://doi.org/10.1007/s11033-018-4323-4

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