Protective Effect of Kaempferol and Its Nanoparticles on 5‐Fluorouracil‐Induced Cardiotoxicity in Rats

Figures

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  Figure 1. Rats were divided into five groups and were injected IP for 14 days. Control group: animals received normal saline. The 5-FU group: animals received IP injection of a single dose of 5-FU (100 mg/kg) only on the first day. The vitamin C group: the group received 5-FU at a single dose of 100 mg/kg body weight only on the first day of treatment and from day 2 onwards alone, rats were injected with 10 mg/kg/day of vitamin C for 14 days. The KPF treatment group: animals received a single dose of 5-FU (100 mg/kg) only on the first day of treatment and from day 2 onwards alone, rats were injected with 1 mg/kg/day of KPF for 14 days. The KPF-NP treatment group: animals received a single dose of 5-FU (100 mg/kg) only on the first day of treatment and from day 2 onwards alone, rats were injected with 1 mg/kg/day of KPF-NPs for 14 days. The hearts of the animals were then analyzed (number of animals in each group: 6).

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  Figure 2. (a) Scanning electron microscopy images. Morphology of KPF-NPs. (b) 88.2% of the nanoparticles are in the first peak and have 212.6 nm. 11.8% have a size of 9.365 nm, which is seen in the second peak. (b) The analysis of HPLC. Curves of 10 ppm standard and 40 ppm KPF loaded Cs-STPP NPs.

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  Figure 3. Comparison of the body weight changes in rats of different groups on the first day before injection and the 14th day after injection. All results are expressed as mean ± SD. ∗P < 0.05 significant compared to the normal group. SD: standard deviation (number of animals in each group: 6).

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  Figure 4. Data quantification indicates the effect of treated groups on blood factors and the comparison of different groups with each other. ∗P < 0.05, ∗∗∗P < 0.001 significantly compared with the normal group..#P < 0.05, ##P < 0.01, ###P < 0.001 significantly compared to the 5-FU group. All results are presented as mean ± standard deviation. RBC: red blood cell; WBC: white blood cell (number of animals: 6).

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  Figure 5. Data quantification indicates the effect of treated groups on cardiac enzyme levels and the comparison of different groups with each other. ∗∗∗P < 0.001 significantly compared to the normal group..#P < 0.05, ##P < 0.01, ###P < 0.001 significantly compared to the 5-FU group. Results are presented as mean ± standard deviation. AST: aspartate transaminase; LDH: lactate dehydrogenase; CK-MB: creatine kinase-MB (number of animals: 6).

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  Figure 6. The effect of KPF and KPF-NP administration on oxidative stress values and total antioxidant capacity and comparison of different groups with each other. ∗P < 0.05, ∗∗∗P < 0.001 significantly compared with the normal group. #P < 0.05 significantly compared to the 5-FU group. All results are presented as mean ± SD. MDA: malondialdehyde; TAC: total antioxidant capacity; SD: standard deviation (number of animals: 6).

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  Figure 7. Histopathological changes of heart tissue. (a) Normal group: normal tissue conditions. (b) 5-FU group: hyperemia (right arrow), necrosis (up arrow), and hyaline (left arrow). (c) 5-FU group and 10 mg vitamin: hyperemia (right arrow), necrosis (up arrow), and hyaline (left arrow). (d) 5-FU and 1 mg/kg KPF-NP group: necrosis (up arrow). (e) 5-FU and 1 mg/kg KPF group: hyperemia (right arrow), necrosis (flash up) above, H&E coloring, and magnification: ×40 (bar = 100 μm).

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  Figure 8. The effect of KPF and KPF-NP administration on the expression of genes related to angiogenesis such as COX-2 and VEGF and then comparison of different groups with each other. ∗P < 0.05 significantly compared to the normal group. #P < 0.05, ##P < 0.01 significantly compared to the 5-FU group. &P < 0.05 significant comparison between the 5-FU+10 mg vitamin C group and 5-FU+ 1 mg KPF group. All results are expressed as mean ± SD. COX: cyclooxygenase; VEGF: vascular endothelial growth factor; SD: standard deviation (number of animals: 6).