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Protective impact of lycopene on ethinylestradiol-induced cholestasis in rats

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Abstract

Protection against cholestasis and its consequences are considered an essential issue to improve the quality of a patient’s life and reduce the number of death every year from liver diseases. Lycopene, a natural carotenoid, has antioxidant scavenger capacity and inhibits inflammation in many experimental models. The present study aimed to elucidate the potential protective effects of lycopene, in comparison to silymarin, in a rat model of cholestatic liver. Animals were daily injected with 17α-ethinylestradiol (EE; 5 mg/kg) for 18 successive days. Silymarin (100 mg/kg) and lycopene (10 mg/kg) were orally administered once per day through the experimental period. Lycopene significantly decreased the EE-induced rise in the serum levels of total bile acid and total bilirubin as well as the activities of alanine aminotransaminase, aspartate aminotransaminase, alkaline phosphatase, and gamma-glutamyl transaminase. Moreover, lycopene reduced the hepatic levels of thiobarbituric acid reactive substances and tumor necrosis factor-α as well as the hepatic activity of myeloperoxidase that were markedly elevated by EE. Lycopene increased the hepatic levels of total protein and albumin and reduced glutathione. In addition, lycopene improved the hepatic histopathological changes induced by EE. These protective effects of lycopene were comparable to that of silymarin. In conclusion, lycopene was effective in protecting against estrogen-induced cholestatic liver injury through its antioxidant and anti-inflammatory activities. Therefore, lycopene might be a potentially effective drug for protection against cholestasis in susceptible women during pregnancy, administration of oral contraceptives, or postmenopausal replacement therapy.

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Acknowledgments

The authors would like to thank Prof. Adel Bakear and Prof. Kawkab A. Ahmed (Pathology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt) for his assistance in the histopathological examinations.

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Authors and Affiliations

  1. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Walaa Wadie & Helmy Moawad Sayed

  2. Department of Pharmacology, National Organization for Drug Control and Research (NODCAR), Giza, Egypt

    Aya Hamada Mohamed, Marwa Ashour Masoud & Hanan Amin Rizk

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  1. Walaa Wadie
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  2. Aya Hamada Mohamed
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  3. Marwa Ashour Masoud
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  4. Hanan Amin Rizk
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Contributions

HMS and WW conceived and designed research. AHM, MAM, and HAR conducted the experiments. AHM analyzed data. AHM and WW wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

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Correspondence to Walaa Wadie.

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The authors declare that they have no conflict of interest.

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The investigation complies with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication no. 85–23, revised 1996) and was approved by the Ethical Committee for Animal Experimentation at Faculty of Pharmacy, Cairo University (Permit Number: PT1775). This article does not contain any studies with human participants.

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Wadie, W., Mohamed, A.H., Masoud, M.A. et al. Protective impact of lycopene on ethinylestradiol-induced cholestasis in rats. Naunyn-Schmiedeberg's Arch Pharmacol 394, 447–455 (2021). https://doi.org/10.1007/s00210-020-01980-5

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