Abstract
This study evaluated the protective effect of kaempferol, a natural flavonoid, against cadmium chloride (CdCl2)-induced liver damage and examined the possible anti-inflammatory and antioxidant mechanisms of protection. Adult male rats were divided into 4 groups (each of 8 rats) as control, kaempferol (50 mg/kg/day orally), CdCl2 (15 ppm/day), and CdCl2 (15 ppm/day) + kaempferol (50 mg/kg/day). All treatments were given for 30 days. With no effect on attenuating the reduced food intake, kaempferol significantly increased body weight and lowered serum levels of liver injury markers including bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase 1 (γ-GTT1) in the CdCl2-treated rats. It also restored normal liver architectures, prevented hepatocyte, loss, and swelling and reduced inflammatory cell infiltration. These effects were associated with a reduction in mitochondrial permeability transition pore, as well as in the expression of cytochrome-c and cleaved caspase-3, markers of mitochondrial damage, and intrinsic cell death. In both the control positive and CdCl2-treated rats, kaempferol significantly lowered the hepatic levels of reactive oxygen species, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), Interleukine-6 (IL-6), and the nuclear activity and localization of NF-κB p65. Besides, kaempferol significantly increased the hepatic total and nuclear levels of the nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1, as well as levels of superoxide dismutase (SOD) and reduced glutathione (GSH) but reduced the cytoplasmic protein levels of keap1. In conclusion, the protective effect of kaempferol against CdCl2-induced hepatic damage is mediated by antioxidant and anti-inflammatory effects driven by upregulating Nrf2/HO-1 axis and suppressing the NF-κB p65 and keap1.
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Data availability
The data used to support the findings of this study are available from the corresponding author upon request.
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This study was supported by the deanship of Scientific Research at King Khalid University, Abha, KSA under grant number (R.G.P1 /227/41). Also, this research was funded by the Taif University Researchers Supporting under grant number (TURSP-2020/99), Taif University, Taif, Saudi Arabia. Also, this research work was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, through the Fast-track Research Funding Program.
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Ali S. Alshehri: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Supervision, Project administration, Funding acquisition, Writing—original draft. Mohamed S A. El-Gerbed and Heba S. Khalifa: Conceptualization, Validation, Formal analysis, Investigation, Writing—original draft. Ayman E. El-Kenawy and Attalla F. El-Kott: Conceptualization, Investigation, Methodology, Writing—review and editing. Ghadeer M. Albadrani: Investigation, Methodology, Writing—review and editing
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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 the King Khalid University (Ethical number ECM#2020-1701). All authors equally participate in the study.
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Alshehri, A.S., El-kott, A.F., El-Gerbed, M.S.A. et al. Kaempferol prevents cadmium chloride-induced liver damage by upregulating Nrf2 and suppressing NF-κB and keap1. Environ Sci Pollut Res 29, 13917–13929 (2022). https://doi.org/10.1007/s11356-021-16711-3
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DOI: https://doi.org/10.1007/s11356-021-16711-3