Effects of apigenin, hesperidin and their combinations on different physiopathological pathways in 5-fluorouracil-induced pulmonary damage

Background: Chemotherapeutics target cancerous cells, but they also have unavoidable toxicities in healthy tissues. Aim: In this study, the effects of the commonly used chemotherapeutic 5-fluorouracil (5FU) on lung tissue were investigated, along with the possible protective benefits of apigenin (API), hesperidin (HES), and their combination. Methodology: The study consisted of control, 5FU, API + 5FU, HES + 5FU, and API+HES + 5FU groups. API 50 mg/kg and HES 200 mg/kg were administered for 7 days. On the 8th day, 5FU was administered a dose of 100 mg/kg. Results: Analyses showed that API and HES were effective in preventing oxidative stress induced by 5FU in lung tissue, attenuating inflammation and apoptosis by suppressing MAPK/NFκB and Caspase-3/Bax/Bcl-2 pathways, suppressing autophagy by decreasing LC3B expression, and regulating Sigmar1 expression. Conclusion: These results suggest that the two flavonoids, when administered separately or in combination, may be useful in reducing side effects that often occur during the use of chemotherapeutics. © 2025 Informa UK Limited, trading as Taylor & Francis Group.