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The ameliorative effect of kaempferol against CdCl2- mediated renal damage entails activation of Nrf2 and inhibition of NF-kB

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Abstract

This study evaluated the nephroprotective effect of kaempferol against cadmium chloride (CdCl2) -induced nephropathy in rats. It also investigated if activation of Nrf2 is a common mechanism of action. Adult male rats ((150 ± 15 g) were divided into 4 groups (n = 8/each) as a control (1% DMSO, orally), control + kaempferol (200 mg/kg, orally), CdCl2 (50 mg/l in drinking water), and CdCl2 + kaempferol (200 mg/kg)-treated rats. All treatments were conducted for 8 weeks. Kaempferol significantly attenuated CdCl2-induced weight loss, reduction in kidney weights, and the injury in the glomeruli, proximal tubules, and distal tubules in the treated rats. It also significantly lowered serum levels of urea and creatinine, increased urine output and urinary creatinine levels and clearance but reduced urinary levels of albumin urinary albumin exertion (UAER), and urinary albumin/creatinine ratio (UACR) in these rats. In parallel, kaempferol downregulated renal levels of cleaved caspase-3 and Bax and unregulated those of Bcl2. In the kidney tissues of the control animals and CdCl2 rats, kaempferol significantly attenuated oxidative stress, inflammation and significantly boosted levels of manganese superoxide dismutase and glutathione. Also, and in both groups, kaempferol suppressed the nuclear levels of NF-κB p65, downregulated Keap1, and stimulated the nuclear activation and protein levels of Nrf2. In conclusion, kaempferol is a potential therapeutic drug to prevent CdCl2-induced nephropathy due to its anti-inflammatory and anti-oxidant effects mediated by suppressing NF- NF-κB p65 and transactivating Nrf2.

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Funding

This study was supported by the deanship of Scientific Research at King Khalid University, Abha, KSA, under grant number (R.G.P2 /35/43). Also, this research was funded by the Taif University Researchers Supporting program under grant number (TURSP-2020/99), Taif University, Taif, Saudi Arabia.

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Authors and Affiliations

  1. Department of Biology, College of Science, King Khalid University, Abha, 61421, Saudi Arabia

    Ali S. Alshehri, Attalla F. El-Kott, Kareem Morsy, Eman R. Ebealy & Essam H. Ibrahim

  2. Department of Zoology, Faculty of Science, Damanhour University, Damanhour, 22511, Egypt

    Attalla F. El-Kott & Heba S. Khalifa

  3. Department of Pathology, College of Medicine, Taif University, Taif, 21944, Saudi Arabia

    Ayman E. El-Kenawy

  4. Department of Anatomy, College of Medicine, King Khalid University, P.O. Box 62529, Abha, Saudi Arabia

    Mohamed Samir A. Zaki

  5. Department of Histology and Cell Biology, College of Medicine, Zagazig University, P.O. Box 31527, Zagazig, Egypt

    Mohamed Samir A. Zaki

  6. Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt

    Kareem Morsy

  7. Department of Oral Biology, Faculty of Oral and Dental Medicine, Delta University for Science and Technology, Gamasa, Egypt

    Reham A. Ghanem

  8. Department of Basic Sciences, Faculty of Physical Therapy, Horus University, New Damietta, 34518, Egypt

    Eman T. Salem

  9. Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah, 21589, Saudi Arabia

    Ahmed E. Altyar

  10. Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, 11474, Riyadh, Saudi Arabia

    Hussah I. M. AlGwaiz

  11. Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia

    Essam H. Ibrahim

  12. Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, 12611, Cairo, Egypt

    Essam H. Ibrahim

  13. Department of Zoology, College of Science, Fayoum University, Fayoum, Egypt

    Mohammed S. Mahmoud & Eman M. Abd-Ella

  14. Department of Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia

    Mohammad A. Dallak

  15. Department of Biology, College of Science and Art, Al-Baha University, Al-Mandaq, Saudi Arabia

    Eman M. Abd-Ella

Authors
  1. Ali S. Alshehri
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  2. Attalla F. El-Kott
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Contributions

ASA, AFE, and AEE: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Supervision, Project administration, Funding acquisition, Writing—original draft. MSAZ, KM, RAG, MAD, MSM, and ETS: Conceptualization, Validation, Formal analysis, Investigation, Writing—original draft. ERE, EHI, HSK and AEA, MSM, HIMA: Conceptualization, Investigation, Methodology, Writing—review & editing. ASA, AFE, AEE, and EMA: Investigation, Methodology, Writing—review & editing.

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Correspondence to Attalla F. El-Kott.

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All applicable international, national, and/or institutional guidelines for the care and use of animals and cell lines were followed and approved by the ethics committee at King Khalid University.

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Alshehri, A.S., El-Kott, A.F., El-Kenawy, A.E. et al. The ameliorative effect of kaempferol against CdCl2- mediated renal damage entails activation of Nrf2 and inhibition of NF-kB. Environ Sci Pollut Res 29, 57591–57602 (2022). https://doi.org/10.1007/s11356-022-19876-7

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