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2-Methoxyestradiol attenuates liver fibrosis in mice: implications for M2 macrophages

  • Thikryat Neamatallah
  • Ashraf B. Abdel-Naim
  • Basma G. Eid
  • Atif Hasan
Original Article

Abstract

Liver fibrosis is a major health problem worldwide due to its serious complications including cirrhosis and liver cancer. 2-Methoxyestradiol (2-ME) is an end metabolite of estradiol with anti-proliferative, antioxidant, and anti-inflammatory activities. However, the protective role of 2-ME in liver fibrosis has not been fully investigated. The aim of this study was to determine the protective effect of 2-ME in carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Animals were injected intraperitoneally with CCl4 twice weekly for 6 weeks. 2-ME 50 mg/kg or 100 mg/kg was administrated intraperitoneally every day over the same period. Our data showed that 2-ME reduced the extent of liver toxicity and fibrosis due to CCl4 exposure. It restored the elevated serum liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels and ameliorated oxidative status. In addition, 2-ME significantly reduced collagen deposition and alpha-smooth muscle actin (α-SMA) protein expressions. Furthermore, 2-ME markedly lowered macrophage infiltration and macrophage alternative activation marker chitinase-like molecules (CHI3L3/YM1). The results of this study indicate an important protective activity of 2-ME in liver fibrosis and highlight the role of macrophage recruitment and alternative activation as a possible target.

Keywords

2-Methoxyestradiol Liver fibrosis Carbon tetrachloride Macrophages Alternative activation 

Notes

Acknowledgments

The project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. G-252-249-38. The authors, therefore, acknowledge with thanks DSR for technical and financial support.

Author contribution

TN and AA conceived and designed research. AA and AH participated in the biochemical and immunohistochemical studies. BE contributed new reagents and antibodies. TN performed the real-time polymerase chain reaction. TN, BE, and AA analyzed the data. TN wrote the manuscript. All authors revised and approved the manuscript.

Funding information

The project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. (G-252-249-38).

Compliance with ethical standards

The study was carried out in accordance with ethical standards in all aspects.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

210_2018_1577_MOESM1_ESM.docx (171 kb)
ESM 1 (DOCX 170 kb)

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  67. DOI: 10.7150/ijbs.7.1273Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Thikryat Neamatallah
    • 1
  • Ashraf B. Abdel-Naim
    • 1
  • Basma G. Eid
    • 1
  • Atif Hasan
    • 2
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyKing Abdulaziz UniversityJeddahSaudi Arabia
  2. 2.Department of Anatomy and Embryology, Faculty of Veterinary MedicineKafrelsheikh UniversityKafrelsheikhEgypt

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