Protective effect of rosmarinic acid against 5-fluorouracil-induced cardiotoxicity in mice via modulation of inflammation, oxidative stress, and apoptosis and restoration of NRF2/HO-1
Main Article Content
Keywords
antioxidants, cardiotoxicity, inflammation, Nrf2, rosmarinic acid, 5-fluorouracil
Abstract
Plant phytochemicals are bioactive substances that offer various biological and health benefits. The cardiotoxicity of 5-fluorouracil (5-FU) restricts its applicability in cancer treatment. The bioactive rosmarinic acid (RA) is an antioxidant and anti-inflammatory polyphenol. This study elucidated the protective efficacy of RA against 5-FU-associated cardiac injury in mice. Mice received RA (25 or 50 mg/kg, orally) for 10 days and then were treated with 5-FU (150 mg/kg) on the 8th day. 5-FU-intoxicated mice demonstrated higher lactate dehydrogenase, creatine kinase-MB, and troponin I levels with various cardiac histopathological alterations. 5-FU-injected mice showed a significant rise in cardiac protein carbonyl and malondialdehyde, associated with reduced myocardial glutathione content and catalase and superoxide dismutase activities. RA pretreatment of 5-FU-treated mice attenuated cardiac injury, decreased protein carbonyl and MDA levels, and promoted antioxidant defense mechanisms in the myocardium. Furthermore, RA significantly reduced cardiac inflammatory response by decreasing the expression of cardiac NF-κB p65 and proinflammatory cytokines in the heart. RA also mitigated 5-FU-induced cardiac apoptosis by attenuation of cardiac levels of Bcl-2, Bax, and caspase-3. It also restored the cardiac Nrf2/HO-1 signaling pathway. Collectively, RA exerts significant cardioprotective effects on 5-FU-induced cardiac injury, and therefore RA could be used as a potential effective adjuvant in alleviating myocardial injury associated with increased oxidative stress and inflammation.
References
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Almuqati, A. F. (2025). Protective effect of rosmarinic acid against 5-fluorouracil-induced cardiotoxicity in mice via modulation of inflammation, oxidative stress, and apoptosis and restoration of NRF2/HO-1. Italian Journal of Food Science, 37(2), 51-64. https://doi.org/10.15586/ijfs.v37i2.2935
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Almuqati, A. F. (2025). Protective effect of rosmarinic acid against 5-fluorouracil-induced cardiotoxicity in mice via modulation of inflammation, oxidative stress, and apoptosis and restoration of NRF2/HO-1. Italian Journal of Food Science, 37(2), 51-64. https://doi.org/10.15586/ijfs.v37i2.2935