Ginkgo biloba attenuated hepatotoxicity induced by combined exposure to cadmium and fluoride via modulating the redox im
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ORIGINAL ARTICLE
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 Milad Arab‑Nozari1,2 · Nematollah Ahangar3 · Ebrahim Mohammadi4 · Zahra Lorigooini5 · Mohammad Shokrzadeh6,7 · Fereshteh Talebpour Amiri8 · Fatemeh Shaki6,7 Received: 26 March 2020 / Accepted: 28 August 2020 © Springer Nature B.V. 2020
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, antiinflammatory, mitochondrial protection and anti-apoptotic effects. Keywords Ginkgo biloba · Cadmium · Fluoride · Oxidative stress · Inflammation · Mitochondrial apoptosis
Introduction Cadmium (Cd) as a well-known heavy metal is one of the most potent environmental contaminants, which has been reported to can induce various health problems even at low level exposure [1]. Fluoride (F) is a natural occurring anion that has widely used in pharmaceutical preparations, * Fatemeh Shaki [email protected] 1
pesticide and agriculture [2]. Exposure to multiple environmental pollutants with similar mechanisms of toxicity, often indicates greater adverse manifestations in comparison with their individual effects, due to the synergistic or additive interaction between them. In an experimental study, it was demonstrated that co-exposure to bisphenol A and titanium
5
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
6
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Islamic Azad University, Ayatollah Amoli Branch, Amol, Iran
Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran Univers
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