Abstract
Background and Objective. 5-Fluorouracil is one of the most common chemotherapeutic agents used in the treatment of solid tumors. 5-Fluorouracil-associated cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Colchicine is a strong anti-inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. And also, its protective effects on cardiovascular disease have been reported in various studies. The current study is aimed at appraising the effect of colchicine on 5-fluorouracil-induced cardiotoxicity in rats. Methods. Twenty male Wistar rats were divided into four groups as follows: control, 5-fluorouracil, colchicine (5 mg/kg), and 5-fluorouracil+5 mg/kg colchicine. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-fluorouracil (100 mg/kg). The control group received normal saline, and the treatment groups received colchicine with an intraperitoneal injection for 14 days. Findings. 5-Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase-2 and tumor necrosis factor-alpha expression, cardiac enzymes, and histopathological degenerations. 5-Fluorouracil treatment also decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. In addition, 5-fluorouracil disrupted electrocardiographic parameters, including increased elevation in the ST segment and increased QRS duration. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase-2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Moreover, body weight loss was hampered after treatment with colchicine. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5-fluorouracil in rats.
Highlights
Pyrimidine 5-fluorouracil (5-FU) is one of the most broadly used chemotherapeutic drugs through intravenous injection to treat a variety of cancers, especially cancer of the gastrointestinal tract, skin, and breast [1, 2]. 5-FU exerts its anticancer impacts in a number of ways, including inhibition of the thymidylate synthase enzyme [3, 4] and activation of protein p53, as well as an effect on cell cycle regulation and G1/S arrest [5].Apart from its benefits, this drug leads to implications in a range of patients’ organs undergoing chemotherapy, such as myelosuppression, emesis, mucositis, nausea, and toxicity to other organs, mainly the heart [6]
All animals were anesthetized with ketamine and xylazine (75/25 mg/kg, i.p.), subcutaneous peripheral limb electrodes were inserted for standard limb lead II recording, and ECG parameters such as ST-elevation, QTc duration, QRS duration, RR interval, and heart rate (HR) with the use of electrocardiographs were measured
The results showed that there was a significant increase in the expression of COX-2 (P < 0:001, P < 0:01) and TNF-α genes (P < 0:001, P < 0:01) in the 5-FU group compared to the control and COL groups (Figure 7)
Summary
Pyrimidine 5-fluorouracil (5-FU) is one of the most broadly used chemotherapeutic drugs through intravenous injection to treat a variety of cancers, especially cancer of the gastrointestinal tract, skin, and breast [1, 2]. 5-FU exerts its anticancer impacts in a number of ways, including inhibition of the thymidylate synthase enzyme [3, 4] and activation of protein p53, as well as an effect on cell cycle regulation and G1/S arrest [5].Apart from its benefits, this drug leads to implications in a range of patients’ organs undergoing chemotherapy, such as myelosuppression, emesis, mucositis, nausea, and toxicity to other organs, mainly the heart [6]. Colchicine is a strong anti-inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. The current study is aimed at appraising the effect of colchicine on 5-fluorouracil-induced cardiotoxicity in rats. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-fluorouracil (100 mg/ kg). 5-Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase-2 and tumor necrosis factor-alpha expression, cardiac enzymes, and histopathological degenerations. 5-Fluorouracil treatment decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase-2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5-fluorouracil in rats
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