ArticleAmerican journal of cancer research2025
Exercise pre-conditioning prevents vascular toxicity caused by infusion of 5-fluorouracil in male rats.
Article in American journal of cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
5-fluorouracil (5-FU) is one of the most common chemotherapies used in cancer treatment yet is often associated with acute cardiotoxicity (e.g., angina, vasospasm). To date, countermeasures to prevent 5-FU cardiotoxicity are lacking. Therefore, we tested the hypothesis that short-term, moderate-intensity exercise completed before 5-FU administration would prevent 5-FU-induced alterations in vascular and cardiac function. Male Sprague-Dawley rats were randomized to sedentary control (SEDCON, n = 9), sedentary 5-FU (SED5FU, n = 10), exercise control (EXCON, n = 8) or exercise 5-FU (EX5FU, n = 8) groups. Rats remained sedentary or completed 4-days of treadmill running (20-25 min, 20 m/min, 5% grade) with the final bout ending ~90-min before treatment with a clinically relevant dose of 5-FU (50 mg/kg bolus + 265 mg/kg 2-hr infusion) or volume matched saline. Echocardiographic indices of left ventricular function and Doppler measurements of aortic pulse wave velocity (PWV) were completed at baseline (BL) and after the 2-hr (2-hr) infusion. 5-FU did not induce changes in left ventricular function. PWV increased from BL to 2-hr in SED5FU (BL: 396 ± 39 cm/s; 2-hr: 452 ± 54 cm/s; P = 0.002), but not SEDCON (BL: 417 ± 55 cm/s; 2-hr: 392 ± 64 cm/s; P = 0.35), EXCON (BL: 408 ± 35 cm/s; 2-hr: 410 ± 46 cm/s; P > 0.99), or EX5FU (BL: 398 ± 13 cm/s; 2-hr: 417± 23 cm/s; P = 0.67). Additionally, PWV at the 2-hr time point was significantly higher in SED5FU compared to SEDCON (P = 0.002). These findings suggest that moderate-intensity exercise preconditioning may protect against 5-FU-induced alterations in arterial PWV-potentially mitigating early signs of cardiotoxicity. Future studies are warranted to identify the mechanisms of 5-FU-induced cardiotoxicity and the feasibility and efficacy of pre-treatment exercise regimens in human patients.
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