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

Abstract

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.

Cardioprotective effect of silymarin nanoemulsion on 5‐fluorouracil‐induced cardiotoxicity in rats

“…In this study, consistent with our other studies, [35,36] 5-FU-treated rats showed a substantial reduction in body weight compared with the control group. According to previous studies, 5-FU-treated rats showed a decrease in food intake, and a significant decrease in body weight, which could be due to internal damage to organs like the liver, [37] or intestine and a decrease in anaerobic bacteria in the gut.…”

A comprehensive and mechanistic review on protective effects of kaempferol against natural and chemical toxins: Role of NF‐κB inhibition and Nrf2 activation

“…Kaempferol and its nanoparticles increased blood factors such as RBC, WBC, HB, and PLT while reducing AST, ALT, LDH, CK, CKMB, and oxidative stress. Also, these compounds decreased the expression of COX‐2 and elevated VEGF expression and SOD and catalase levels 121 . In addition, other studies have revealed that kaempferol ameliorated cardiac function by elevation of cardiac enzymes and decreasing COX‐2 (Tables 3 and 4).…”

“…Also, these compounds decreased the expression of COX-2 and elevated VEGF expression and SOD and catalase levels. 121 In addition, other studies have revealed that kaempferol ameliorated cardiac function by elevation of cardiac enzymes and decreasing COX-2 (Tables 3 and 4). [122][123][124]…”

Kaempferol's potential effects againstSARS‐CoV‐2 andCOVID‐19‐associated cancer progression and chemo‐resistance

“…Although, tissue damage, hepatotoxicity, and cardiac toxicity reduction were unknown as undeniable side effects of cytotoxic drugs during cancer therapy, a timely treatment combination including: chemotherapy, radiation, and surgery along with beneficial adjuvants can improve efficiency the cancer therapies. For example, a report has proven that treating kaempferol-anoparticle specifically improved cardiotoxicity induced by 5-Fluorouracil in an animal model (Safarpour et al, 2022).…”