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Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions

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11 April 2024 Editor's Note: Readers are alerted that the concerns have been raised with this article. Editorial action will be taken as appropriate once this matter is resolved and all parties have been given an opportunity to respond in full.

Abstract

The current study was prepared to assess the underlying mechanism of diclofenac (Diclo)-stimulated renal oxidative damage (50 mg/kg/day for two consecutive days I.P) and antioxidative, and antiapoptotic effects of Thymoquinone (20 mg/kg/day for 21 days P.O). Exposure of rats to Diclo significantly increased serum urea and creatinine, decreased GSH, catalase, and total antioxidant capacity with a concomitant increase of lipid peroxidation. Diclo significantly decreased renal mitochondrial viability %, increased DNA fragmentation %, caspase 3 activity, and cytochrome C (Cyt C) concentration. Molecular investigations revealed that Diclo administration caused a significant reduction of mitofusin-2 (Mfn2) and increase of microRNA-34a (miR-34a) mRNA expressions with a concomitant decrease of Nrf2 and HO-1 mRNA expressions/protein levels and increase of NF-κB mRNA expressions. Thymoquinone restored renal oxidative/antioxidant redox. Thymoquinone significantly increased the renal mitochondrial viability % and reduced renal DNA fragmentation %, caspase 3 activity, and Cyt C. Moreover, thymoquinone modulated renal Mfn2 and miR-34a as compared to Diclo group. Our findings were confirmed by immunohistochemical assays for detecting the iNOS and NOX4 in renal tissue as well as histopathological investigations. Obtained results demonstrated that thymoquinone possess a potential antioxidant, antiapoptotic defense and exhibited a strong nephroprotective activity against Diclo-induced toxicity.

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  • 11 April 2024

    Editor's Note: Readers are alerted that the concerns have been raised with this article. Editorial action will be taken as appropriate once this matter is resolved and all parties have been given an opportunity to respond in full.

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Acknowledgment

All authors thank staff members of Biochemistry Department, Faculty of Veterinary Medicine, and Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University for their help. Moreover, this work was supported by King Saud University, Deanship of Scientific Research, College of Science Research Center.

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, 62511, Egypt

    Khalid Shaaban Hashem & Eman T. Mohammed

  2. Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt

    Ahmed Zakaria Abdelazem & Amr M. Nagi

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

    Marwa Abdeltawab Mohammed

  4. Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Basma Emad Aboulhoda

  5. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Mohamed M. Abdel-Daim

  6. Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, 41522, Ismailia, Egypt

    Mohamed M. Abdel-Daim

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  1. Khalid Shaaban Hashem
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Contributions

Khalid S. Hashem Ahmed did the experiment, analysis of data, and writing the manuscript. Zakaria Abdelazem helped in the experiment and the analysis of data. Marwa Abdeltawab Mohammed shared in the methodology of the experiment and writing processes. Amr M. Nagi helped in the experiment, analysis of data, and writing. Basma Emad Aboulhoda did the pathological study and analysis. Eman T. Mohammed and Mohamed M. Abdel-Daim shared in the writing processes and proofreading of the manuscript.

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Correspondence to Khalid Shaaban Hashem.

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Hashem, K.S., Abdelazem, A.Z., Mohammed, M.A. et al. Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions. Environ Sci Pollut Res 28, 10100–10113 (2021). https://doi.org/10.1007/s11356-020-11313-x

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