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Protective effects of zingerone on cisplatin-induced nephrotoxicity in female rats

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Abstract

Zingerone (ZO), one of the active components of ginger (Zingiber officinale), is a phenolic alkanone with antioxidant, antiapoptotic, and anti-inflammatory properties. Cisplatin (CP) is a widely used chemotherapeutic drug for solid tumors, but its therapeutic use is limited due to dose-dependent nephrotoxicity. In the present study, we investigated the ameliorative effect of ZO against CP-induced nephrotoxicity. Intraperitoneal administration of single-dose CP (7 mg/kg body weight) on the first day enhanced kidney lipid peroxidation and reduced antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). CP increased serum urea and creatinine levels and disrupted histological integrity while causing a decrease aquaporin 1 (AQP1) level in the kidney tissues. CP induced inflammatory responses by elevating the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-33 (IL-33) and nuclear factor kappa B (NF-κB), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it also caused oxidative DNA damage and activation of apoptotic pathway by increasing of 8-hydroxy-2′-deoxyguanosine (8-OHdG), p53, cysteine aspartate-specific protease-3 (caspase-3), and Bcl-2-associated x protein (bax) while decreasing B cell lymphoma-2 (Bcl-2). However, treatment with ZO at a dose of 25 and 50 mg/kg b.wt. for 7 days significantly decreased oxidative stress, apoptosis, inflammation, and histopathological alterations while increased AQP1 levels in the kidney tissue. The results of the current study suggested that ZO as an effective natural product attenuates CP-induced nephrotoxicity.

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Acknowledgments

We are indebted to Prof. Dr. Erdal Kaygusuzoglu at the Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Bingol University for his contribution to this study.

Funding

This work was supported by Bingol University, Foundation of Scientific Researches Projects (Project number: BAP-VF.2016.00.001).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey

    Fatih Mehmet Kandemir & Sefa Kucukler

  2. Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey

    Serkan Yildirim & Gizem Eser

  3. Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, 12000, Bingol, Turkey

    Cuneyt Caglayan

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  1. Fatih Mehmet Kandemir
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  2. Serkan Yildirim
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  3. Cuneyt Caglayan
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  4. Sefa Kucukler
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  5. Gizem Eser
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Corresponding author

Correspondence to Cuneyt Caglayan.

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The committee of Animal Experimentation Ethics, Bingol University, approved the design of the experiments, and the protocol conforms to the guidelines of the National Institutes of Health (NIH) (ethic code number: 2018-9/03).

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Kandemir, F.M., Yildirim, S., Caglayan, C. et al. Protective effects of zingerone on cisplatin-induced nephrotoxicity in female rats. Environ Sci Pollut Res 26, 22562–22574 (2019). https://doi.org/10.1007/s11356-019-05505-3

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