Targeting mitochondrial dysfunction and apoptosis in 5-fluorouracil–induced cardiotoxicity using kaempferol-mediated selenium nanoparticles

Figures

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  Fig. 1. Validation of the molecular docking protocol by re-docking analysis. Superposition of the crystallographic ligand poses (red) and their corresponding top-ranked re-docked poses (blue) within the binding sites of (A) iNOS, (B) GST, and (C) TNF-α. The calculated heavy-atom RMSD values were 0.038, 0.4389, and 0.0783 Å, respectively.

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  Fig. 2. Two-dimensional interaction diagram of Kaempferol docked into the active site of iNOS (PDB ID: 1DD7).

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  Fig. 3. Two-dimensional interaction diagram of Kaempferol docked into the binding site of GST (PDB ID: 1EV4).

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  Fig. 4. Two-dimensional interaction diagram of Kaempferol docked into the TNF-α binding site (PDB ID: 2AZ5).

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  Fig. 5. DLS and zeta potential Description of SeNPs biosynthesized using kaempferol (KMP-SeNPs). (A) particle size distribution by intensity indicating nanoscale size and good dispersion, and (B) Zeta potential distribution showing a highly negative surface charge confirming colloidal stability of KMP-SeNPs.

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  Fig. 6. TEM image of SeNPs biosynthesized using kaempferol (KMP-SeNPs) (scale bar = 100 nm).

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  Fig. 7. Impact of kaempferol and kaempferol-mediated selenium nanoparticles on cardiac injury biomarkers in 5-fluorouracil–treated rats. (A) CK-MB, (B) cardiac troponin I (cTnI), and (C) LDH activities. The data, which includes statistical comparisons between groups, are presented as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 8. Effects of kaempferol and kaempferol-mediated selenium nanoparticles on oxidative stress and antioxidant defense in 5-fluorouracil–induced toxicity. (A) Keap-1, (B) MDA, (C) NO, (D) GSH, (E) SOD, (F) CAT, (G) GR, (I) GPx, and (J) Nrf2 expression. Data are presented as mean ± SEM (n = 5) with statistical comparisons among groups. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 9. Effects of kaempferol and kaempferol-mediated selenium nanoparticles on inflammatory cytokines in 5-fluorouracil–induced toxicity. (A) TNF-α, (B) IL-6, and (C) IL-10 protein values. Data are presented as mean ± SEM (n = 5) with statistical comparisons among groups. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 10. Effects of kaempferol and kaempferol-mediated selenium nanoparticles on gene expression in 5-fluorouracil–induced toxicity. mRNA expression of (A) NF-κB and (B) FOXP3. Data are presented as mean ± SEM (n = 5) with statistical comparisons among groups. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 11. Effects of kaempferol and kaempferol-mediated selenium nanoparticles on apoptotic markers in 5-fluorouracil–induced toxicity. (A) Bax, (B) Caspase-3, and (C) Bcl-2 values in experimental groups. Data are presented as mean ± SEM (n = 5) with statistical comparisons among groups. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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  Fig. 12. Protective effect of KMP-SeNPs on cardiac immunoreactivity of Nrf-2 in 5FU-induced cardiotoxicity in rats. Photomicrographs of tissue of the heart from all cohorts. The reactivity of Nrf-2 was evident in the tissues as a brown tone produced by DAB chromogen. (DAB, ×400). (A) The control group showed normal cardiac muscle structure with moderate Nrf-2 staining. (B) 5FU and (D) Na2SeO3&5FU treated groups revealed weak Nrf-2 immunostaining. In contrast, (C) KMP&5FU group revealed moderate expression, while (E) KMP-SeNP&5FU-treated group displayed moderate Nrf-2 staining. (F) Quantitative assessment of immunostaining region % for Nrf-2 was expressed as mean ± SEM (n = 5). Statistical evaluation utilizing one-way ANOVA accompanied by Duncan’s post hoc analysis. ns: not significant; *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.