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Indole-3-carbinol alleviates carbon tetrachloride-induced liver injury by inhibiting inflammatory response and regulating lipid metabolism

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Abstract

The hepatoprotective effects of indole-3-carbinol (I3C), one of the byproducts of the breakdown of glucosinolate glucobrassicin, were examined in mice with carbon tetrachloride (CCl4)-induced hepatotoxicity. I3C was administered orally at a dose of 50 or 100 mg/kg to C57BL/6 mice for 3 consecutive days with or without a subsequent single oral administration of CCl4 (1.5 mL/kg). I3C treatment significantly suppressed the increases in alanine aminotransferase and aspartate aminotransferase levels in the sera of CCl4-injured mice. In addition, I3C treatment markedly suppressed CCl4-induced hepatic inflammation, by suppressing the activation of macrophages and Kupffer cells in the liver. To examine the effects of I3C on lipid accumulation, 3T3-L1 pre-adipocytes were differentiated with I3C or vehicle control. I3C treatment reduced lipid accumulation, which appeared to be associated with the downregulation of adipogenic transcription factors, such as CCAAT/enhancer-binding protein α, peroxisome proliferator-activated receptor γ, and lipid accumulation-related genes, including adipocyte protein-2. Taken together, the present study suggest that I3C treatment reduces hepatocyte death and lipid accumulation in hepatocytes in CCl4-induced hepatic injury with concurrent suppression of macrophages/Kupffer cells, which was further evidenced by I3C-treated pre-adipocytes in vitro, through downregulation of lipid metabolism.

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Acknowledgements

This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agri-Bio industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (Grant number: 316006-05-1-HD040).

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Authors and Affiliations

  1. Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju, 63243, Republic of Korea

    Meejung Ahn, Jeongtae Kim & Taekyun Shin

  2. Department of Animal Science, College of Life Science, Sangji University, Wonju, 26339, Republic of Korea

    Meejung Ahn

  3. Department of Anatomy, Kosin University College of Medicine, Busan, 49267, Republic of Korea

    Jeongtae Kim

  4. Jeju Biodiversity Research Institute, Jeju Technopark, Seogwipo, Jeju, 63608, Republic of Korea

    Dawun Yang & Gi Ok Kim

  5. Department of Food Bioengineering, College of Engineering, Jeju National University, Jeju, 63243, Republic of Korea

    Ji-Yeon Chun

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  1. Meejung Ahn
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Correspondence to Meejung Ahn or Taekyun Shin.

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Ethical Statement

All experiments that involved animal use were conducted in accordance with the Jeju National University Guidelines for the Care and Use of Laboratory Animals (Permission NO. 2016-0040).

Conflict of interest

Meejung Ahn has no conflict of interest. Jeongtae Kim has no conflict of interest. Dawun Yang has no conflict of interest. Ji-Yeon Chun has no conflict of interest. Gi Ok Kim has no conflict of interest. Taekyun Shin has no conflict of interest.

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Ahn, M., Kim, J., Yang, D. et al. Indole-3-carbinol alleviates carbon tetrachloride-induced liver injury by inhibiting inflammatory response and regulating lipid metabolism. ADV TRADIT MED (ADTM) 21, 371–378 (2021). https://doi.org/10.1007/s13596-020-00452-8

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