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Ginkgo biloba attenuated hepatotoxicity induced by combined exposure to cadmium and fluoride via modulating the redox imbalance, Bax/Bcl-2 and NF-kB signaling pathways in male rats

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Abstract

Aim of this study was to investigate the efficacy of Ginkgo Biloba (G.B) hydro-ethanolic extract against hepatotoxicity induced by combined exposure to cadmium (Cd) and fluoride (F) in Wistar rats. Animals were exposed to F (30 mg/L) + Cd (40 mg/L), F + Cd plus G.B (50,100 and 200 mg/kg), G.B (200 mg/kg), F + Cd plus Vit C(1000 mg/L) in drinking water for 42 days. Significant raise in liver enzymes and histopathological changes were observed in F + Cd treated rats. F + Cd exposure enhanced protein and glutathione oxidation, lipid peroxidation and decreased superoxide dismutase activity. F and Cd combination also caused mitochondrial dysfunction, swelling and mitochondrial membrane potential collapse in liver isolated mitochondria. Up-regulation of inflammatory genes (TNF-α, IL-1β and NF-kB) and pro-apoptotic Bax as well as down-regulation of anti-apoptotic Bcl-2 were detected after co-exposure to F and Cd. Interestingly, G.B alleviated F + Cd induced liver oxidative stress, mitochondrial damage and prevented inflammation and apoptosis. Furthermore, decrease in serum liver enzymes and improvement of histopathologic lesions were observed in G.B treated rats. This study explored the potential beneficial role of G.B on F + Cd combined hepatotoxic effects via considering its possible antioxidant, anti-inflammatory, mitochondrial protection and anti-apoptotic effects.

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Acknowledgements

This study was extracted from PhD thesis of Milad Arab-Nozari and supported by a grant from the Research Council of Mazandaran University of Medical Sciences, Sari, Iran [Grant Number: 1484].

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Authors and Affiliations

  1. Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

    Milad Arab-Nozari

  2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Islamic Azad University, Ayatollah Amoli Branch, Amol, Iran

    Milad Arab-Nozari

  3. Department of Pharmacology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran

    Nematollah Ahangar

  4. Environmental Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Ebrahim Mohammadi

  5. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

    Zahra Lorigooini

  6. Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran

    Mohammad Shokrzadeh & Fatemeh Shaki

  7. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Mohammad Shokrzadeh & Fatemeh Shaki

  8. Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Fereshteh Talebpour Amiri

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  1. Milad Arab-Nozari
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Correspondence to Fatemeh Shaki.

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This research was involved animals and was performed according to ethical protocols approved by the Committee of Animal Experimentation of Mazandaran University of Medical Sciences, Sari, Iran.

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Arab-Nozari, M., Ahangar, N., Mohammadi, E. et al. Ginkgo biloba attenuated hepatotoxicity induced by combined exposure to cadmium and fluoride via modulating the redox imbalance, Bax/Bcl-2 and NF-kB signaling pathways in male rats. Mol Biol Rep 47, 6961–6972 (2020). https://doi.org/10.1007/s11033-020-05755-2

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