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Alleviative effect of licorice on copper chloride-induced oxidative stress in the brain: biochemical, histopathological, immunohistochemical, and genotoxic study

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Abstract

Although copper is an essential micronutrient involved in a variety of biological processes indispensable for sustaining life, it can be toxic when administered in excess. Licorice (Glycyrrhizaglabra) has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. Here, we test the hypothesis that licorice could ameliorate copper-induced neurotoxic and genotoxic effects in adult male albino rats. For this purpose, 48 adult male albino rats were randomized into five groups: group I (8 rats), untreated control; group II (16 rats), subdivided into; vehicle control IIa (8 rats) which received 1 mL saline twice weekly intraperitoneally for 8 weeks and vehicle control IIb (8 rats) received 0.5 mL distilled water/day orally gavaged for 8 weeks; group III (8 rats), treated with licorice dissolved in 0.5 mL of distilled water, 50 mg/kg b.w./day orally gavaged for 8 weeks; group IV (8 rats), copper chloride (CuCl2) dissolved in 0.5 mL saline, 7 mg/kg b.w. twice weekly intraperitoneal for 8 weeks; and group V (8 rats), CuCl2 + licorice (the same previously mentioned doses) licorice extract were orally given for 10 days before treatment was initiated then followed by CuCl2 intraperitoneally for 8 weeks. We found that CuCl2 exposure significantly increased brain oxidative stress as manifested by elevated malondialdehyde levels, decreased reduced glutathione content, and depressed antioxidant enzyme activities in brain tissues when compared with control groups. This was accompanied by histopathological changes in the form of increased cellularity and swelling of astrocytes that showed dense eosinophilic cytoplasm, pyknotic nuclei, and multiple apoptotic bodies that associated with degenerated neurons with deep eosinophilic cytoplasm. Also, strong Bax immunoreactions in the brain were detected. Furthermore, comet assay results confirmed CuCl2-related oxidative DNA damage. Notably, all these changes were partially ameliorated in rats treated concomitantly with licorice and CuCl2. Our results showed that licorice exerts protective effects against CuCl2-induced neuro- and genotoxicities. These effects may be attributed to the antioxidative property of licorice.

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Acknowledgements

Sincere appreciation is expressed to all members in forensic Medicine and Clinical Toxicology Department for their encouragement and special gratefulness for Prof. Dr. Mei Samir for her valuable guidance and support.

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Authors and Affiliations

  1. Departments of Forensic Medicine & Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

    Heba El-Sayed Mostafa & Eman Ahmad Alaa-Eldin

  2. Departments of Community, Environmental & Occupational Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt

    Dalia Abdallah El-Shafei

  3. Departments of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

    Nehal S. Abouhashem

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  1. Heba El-Sayed Mostafa
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  2. Eman Ahmad Alaa-Eldin
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  3. Dalia Abdallah El-Shafei
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  4. Nehal S. Abouhashem
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Correspondence to Eman Ahmad Alaa-Eldin.

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The experiment was carried out in compliance with the guidelines of Institute of Laboratory Animal Resources, Commission on Life Sciences and National Research Council (1996) and the institutional guidelines for the care and use of experimental animals approved by the Medical Research Ethics Committee of Zagazig University, Egypt.

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The authors declare that they have no conflict of interest.

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This study was not funded by any source.

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Responsible editor: Philippe Garrigues

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Mostafa, H.ES., Alaa-Eldin, E.A., El-Shafei, D.A. et al. Alleviative effect of licorice on copper chloride-induced oxidative stress in the brain: biochemical, histopathological, immunohistochemical, and genotoxic study. Environ Sci Pollut Res 24, 18585–18595 (2017). https://doi.org/10.1007/s11356-017-9503-6

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