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Methanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity

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Abstract

Cisplatin (CP) is a powerful anticancer agent used in the treatment of a diverse type of cancers. Oxidative stress is one of the most important side effects limiting the use of cisplatin. The protective effects of methanolic extract (ME) and ephedrine (EP), major compound, of Ephedra alata on CP-induced damages were here assessed. Treatment with CP-induced nephrotoxicity and hepatotoxicity characterized by biochemical alterations. In fact, using CP reduced significantly glutathione (GSH) levels, enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and increased malondialdehyde (MDA) content. Nonetheless, CP-treatment induced DNA damage at renal, hepatic, and blood cells and increased interferon gamma (IFNγ) level in serum. Co-treatments of mice with ME normalized relative kidney/body weight, restored biochemical and oxidative stress parameters, reduced DNA damage and IFNγ level. In conclusion, ME exhibited the best protective effect against CP damage compared with ephedrine. This is could be attributed to the presence of polysaccharides, organic acids, flavonoids, and tannins in addition to ephedrine alkaloids. These compounds were reported to play a major role in inhibiting and scavenging free radicals, providing an effective protection against CP- induced oxidative damage.

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Abbreviations

SOD:

Superoxide dismutase

CAT:

Catalase

GST:

Glutathione-S-transferase

MDA:

Malondialdehyde

IFNγ:

Interferon gamma

ROS:

Reactive oxygen species

DPPH:

1.1-diphenyl-2-picryl-hydrazyl

AST:

Aspartate transaminase

ALT:

Alanine transaminase

CR:

Creatinine

EDTA:

Ethylenediaminetetraacetic acid

CDNB:

1-chloro-2,4-dinitrobenzene

H2O2:

Hydrogen peroxide

DTNB:

5,5′-dithiobis-(2-nitrobenzoic acid)

Na2HPO4:

Sodium phosphate dibasic

TPC:

Total phenolic contents

TFC:

Total flavonoids contents

GAE:

Gallic acid equivalents

RE:

Rutin equivalents

LD50 :

Median lethal dose

TBA:

Thiobarbituric acid

TCA:

Trichloroacetic acid

OD:

Optical density

DMSO:

Dimethyl sulfoxide

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Acknowledgments

The authors acknowledge the “Ministère Tunisien de l’Enseignement Supérieur et de la Recherche Scientifique” for its support.

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Authors and Affiliations

  1. Unit of Bioactive and Natural Substances and Biotechnology UR17ES49, Faculty of Dental Medicine, University of Monastir, Avicenne Street, 5000, Monastir, Tunisia

    Fairouz Sioud, Imene Ben Toumia, Aida Lahmer, Rihab Khlifi, Zaineb Dhaouefi, Mouna Maatouk, Kamel Ghedira & Leila Chekir-Ghedira

  2. Laboratory of Pharmacognosy, Faculty of Pharmacy, University of Monastir, Avicenne Street, 5000, Monastir, Tunisia

    Fairouz Sioud, Imene Ben Toumia, Kamel Ghedira & Leila Chekir-Ghedira

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  1. Fairouz Sioud
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  2. Imene Ben Toumia
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  3. Aida Lahmer
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  4. Rihab Khlifi
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  5. Zaineb Dhaouefi
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  7. Kamel Ghedira
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Correspondence to Fairouz Sioud.

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All experiments were performed in accordance with the guidelines for the care and use of laboratory animals as published by the US National Institute of Health. All experiments received the explicit approval of the Ethics Animal Committee in Tunisia.

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The authors declare that they have no conflict of interest.

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Responsible editor: Philippe Garrigues

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Sioud, F., Ben Toumia, I., Lahmer, A. et al. Methanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity. Environ Sci Pollut Res 27, 12792–12801 (2020). https://doi.org/10.1007/s11356-020-07904-3

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