{"doi":"10.62347/ucjb2516","title":"Exercise pre-conditioning prevents vascular toxicity caused by infusion of 5-fluorouracil in male rats","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.","journal":"American Journal of Cancer Research","year":2025,"id":577443,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1486981,"name":"Stephen T Hammond","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:04.622308Z","pmid":"41113975","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}