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Flavonoids of Haloxylon salicornicum (Rimth) prevent cisplatin-induced acute kidney injury by modulating oxidative stress, inflammation, Nrf2, and SIRT1

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Abstract

Cisplatin (CIS) is an effective chemotherapeutic drug used for the treatment of many types of cancers, but its use is associated with adverse effects. Nephrotoxicity is a serious side effect of CIS and limits its therapeutic utility. Haloxylon salicornicum is a desert shrub used traditionally in the treatment of inflammatory disorders, but neither its flavonoid content nor its protective efficacy against CIS nephrotoxicity has been investigated. In this study, seven flavonoids were isolated from H. salicornicum methanolic extract (HSE) and showed in silico binding affinity with NF-κB, Keap1, and SIRT1. The protective effect of HSE against CIS nephrotoxicity was investigated. Rats received HSE (100, 200, and 400 mg/kg) for 14 days followed by a single injection of CIS. The drug increased Kim-1, BUN, and creatinine and caused multiple histopathological changes. CIS-administered rats showed an increase in renal ROS, MDA, NO, TNF-α, IL-1β, and NF-κB p65. HSE prevented tissue injury, and diminished ROS, NF-κB, and inflammatory mediators. HSE enhanced antioxidants and Bcl-2 and downregulated pro-apoptosis markers. These effects were associated with downregulation of Keap1 and microRNA-34a, and upregulation of SIRT1 and Nrf2/HO-1 signaling. In conclusion, H. salicornicum is rich in flavonoids, and its extract prevented oxidative stress, inflammation, and kidney injury, and modulated Nrf2/HO-1 and SIRT1 signaling in CIS-treated rats.

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Authors and Affiliations

  1. Physiology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Shaymaa A. Ramadan & Madeha A. Ewais

  2. Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt

    Emadeldin M. Kamel

  3. Physiology Department, Faculty of Medicine, Cairo University, Giza, Egypt

    Akef A. Khowailed

  4. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University-Assiut Branch, Asyut, Egypt

    Emad H. M. Hassanein

  5. Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK

    Ayman M. Mahmoud

  6. Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt

    Ayman M. Mahmoud

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  1. Shaymaa A. Ramadan
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Contributions

Conceptualization: A.M.M. Data curation: A.M.M., S.A.R., E.M.K., and E.H.M.H. Formal analysis: A.M.M. Investigation: A.M.M., S.A.R., E.M.K., and E.H.M.H. Methodology: S.A.R., A.M.M.; M.A.E., A.A.K., E.M.K., and E.H.M.H. Project administration: A.M.M. and A.A.K. Resources: A.M.M., M.A.E., and E.M.K. Supervision: A.M.M. Validation: A.M.M. Visualization: A.M.M. Writing—original draft: A.M.M. and E.M.K. Writing—review and editing: A.M.M.

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Correspondence to Ayman M. Mahmoud.

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Ramadan, S.A., Kamel, E.M., Ewais, M.A. et al. Flavonoids of Haloxylon salicornicum (Rimth) prevent cisplatin-induced acute kidney injury by modulating oxidative stress, inflammation, Nrf2, and SIRT1. Environ Sci Pollut Res 30, 49197–49214 (2023). https://doi.org/10.1007/s11356-023-25694-2

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