Antidyslipidemic Effect of 5-Fluorouracil against Cyclophosphamide-Induced Dyslipidemia in Male Albino Rats

Abstract

Background: Cyclophosphamide (CPA) is a drug with a wide spectrum of clinical uses. It is commonly used as anticancer and immuno suppressant agent. It induces hyperlipidemia and myocardium damage. 5-FU is widely used in the treatment of a range of cancers. 5-FU in combination with other chemotherapeutic agents improves response rates and survival in breast and head and neck cancers. Objectives: The present study aimed to evaluate the antidyslipidemic effect of 5-fluorouracil against dyslipidemia induced by cyclophosphamide in male albinorats. Materials and Methods: Twenty-eight male adult rats were grouped randomly into four groups (n=5 for each group). Group II cyclophosphamide (CPA): Cyclophosphamide at a dose of 10 mg/kg day by day through i.p. to rats for 14 days. Group III Fluorouracil (5-FU): 5-Fluorouracil at a dose of 10 mg/kg day by day in saline was given through i.p. to rats for 14 days. Group IV (CPA+5-FU): Rats were given CPA followed by 5-FU at a dose of 10 mg/kg per day (day by day) through i.p. to rats for 14 days. At the end of the experimental period, rats were anesthetized using light ether. Blood samples were taken and prepared for biochemical measurements. Results: Intraperitoneal administration of CPA or 5-FU resulted in a significant increase in the levels of serum lipids. The cholesterol, Triglyceride, and LDL levels in serum of CPA or 5-FU treated rats were significantly increased when compared to controls. When CPA was administered followed by 5-FU prevented the increase in serum lipid levels highlighting its hypolipidemic role as antagonism. Also, a marked decrease in HDL cholesterol was noted in CPA treated rats. These changes produced by CPA to serum levels of HDL were normalized when 5-FU is given to the treated rats compared to CPA administered rats. Conclusion: It could be concluded that treatment of rats with CPA induced dyslipidemia. However, 5-FU and CPA combination could produce a significant amelioration in the dyslipidemic changes, and it may be considered as a potentially useful candidate in the combination chemotherapy with CPA to prevent dyslipidemia. Future work should consider combined chemotherapy regimens, as two or more mechanisms of action of chemotherapeutic drugs could be more powerful than one mechanism.