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

BACKGROUND: Fluorouracil (5-FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5-FU-associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti-inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5-FU-induced cardiotoxicity in rats. METHODS: Thirty Male Wistar rats were divided into five groups as follows: control, 5-FU, 5-FU+10 mg/kg vitamin C, 5-FU+ 1 mg/kg KPF, and 5-FU+ 1 mg/kg KPF-NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF-NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. RESULTS: 5-FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX-2 (cyclooxygenase-2) expression, and histopathological degenerations. 5-FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF-NPs reduced oxidative stress, cardiac enzymes, COX-2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF-NPs. CONCLUSION: Our results demonstrated that treatment with KPF and KPF-NPs significantly improved cardiotoxicity induced by 5-FU in rats.

Evaluating Inhibitory Effects of Paclitaxel and Vitamin D3 Loaded Poly Lactic Glycolic Acid Co-Delivery Nanoparticles on the Breast Cancer Cell Line.

Purpose: Paclitaxel (PTX) has transpired as a significant agent in the treatment of breast cancer. Meanwhile, polylactic glycolic acid (PLGA) nanoparticles (NPs) are able to increase the anticancer effect of the PTX in the blood. Methods: Nano-precipitation was used to prepare the PLGA-PTX-VitD3 co-delivery NPs. Drug loading, encapsulation efficiency, in vitro release profile, cell viability, migration, apoptosis, and bcl2 expression of NPs were evaluated. Results: The average size of co-delivery NPs was 231 ± 46 nm. Observed was a controlled release of the PTX and vitamin D3 from co-delivery NPs between 0.5 and 240 hours. MTT showed the ability of 8 µg.mL-1 of co-delivery NPs to kill 50 % of the MCF-7; likewise, the co-delivery NPs prevented MCF-7 migration. The co-delivery NPs led 46.35 % MCF-7 to enter primary apoptosis. 60.8% of MCF-7 in the control group were able to enter the G (1) phase of the cell cycle. The co-delivery NPs increased expression of bax. In addition to its higher toxicity against MCF-7 than that of PTX, co-delivery NPs were able to release drugs continuously for a long period, which indeed increased the efficiency of the drugs. Conclusion: The effect of co-delivery NPs on MCF-7 cell viability was different from that in other drugs. In fact, the co-deliver NPs were able to release drugs continuously for a long time, this could induce primary apoptosis in the MCF-7 and decrease the metastasis and toxicity of drugs.