Beshel Justin Atiang, Ukweni Samuel Usoh, Okon Idara Asuquo, Owu Daniel Udofia
Department of Physiology, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Nigeria.
Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Western Campus, Bushenyi, Uganda.
Toxicol Rep. 2025 Aug 21;15:102116. doi: 10.1016/j.toxrep.2025.102116. eCollection 2025 Dec.
Naringenin, a major flavonoid in oranges, grapefruit, tomato skin and apocynin a polyphenolic compound isolated from plants, such as are known to possess anti-oxidant, anti-inflammatory, and anti-cancer properties. Doxorubicin (DOX) is an antibiotic, effective in the treatment of cancer, but notorious for its propensity to cause cardiotoxicity. This study investigated the combined effects of naringenin and apocynin in DOX-induced cardiac toxicity. Thirty rats were randomly divided into five groups (n = 6) as follows: Normal Control (NC), DOX only, DOX+ naringenin, DOX + apocynin and DOX +naringenin + apocynin. DOX (2.5 mg/kg) was administered intraperitoneally, three times per week for two weeks (cumulative dose of 15 mg/kg). Naringenin (50 mg/kg/day) and apocynin (25 mg/kg/day) were administered orally. ECG measurements were carried out and heart homogenates were used to estimate cardiac inflammatory (IL-6, CRP), cardiac toxicity (CTnT, LDH, CKMB) and hypertensive (NO, ACE) markers. Histopathological examination of the heart was performed. Doxorubicin significantly altered the ECG with large T-wave, ST-elevation and wide QRS-complex. Results also showed significant changes in cardiac inflammatory and hypertensive biomarkers. Naringenin and apocynin treatment significantly attenuated the impact of doxorubicin on rats ECG, decreased biomarkers levels of cardiac inflammatory and hypertensive biomarkers. The cytoarchitecture of heart significantly improved in naringenin and apocynin treated groups, when compared to DOX only group. This study indicates that administration of naringenin and apocynin have cardioprotective ability and also ameliorated cardiotoxicity-induced by doxorubicin probably due to its anti-inflammatory and free radical scavenging properties.
柚皮素是橙子、葡萄柚、番茄皮中的一种主要类黄酮，而从植物中分离出的多酚化合物阿朴色原酮，例如已知具有抗氧化、抗炎和抗癌特性。阿霉素（DOX）是一种抗生素，对癌症治疗有效，但因其易导致心脏毒性而声名狼藉。本研究调查了柚皮素和阿朴色原酮对阿霉素诱导的心脏毒性的联合作用。30只大鼠随机分为五组（n = 6），如下：正常对照组（NC）、仅阿霉素组、阿霉素 + 柚皮素组、阿霉素 + 阿朴色原酮组和阿霉素 + 柚皮素 + 阿朴色原酮组。阿霉素（2.5 mg/kg）腹腔注射，每周三次，共两周（累积剂量15 mg/kg）。柚皮素（50 mg/kg/天）和阿朴色原酮（25 mg/kg/天）口服给药。进行心电图测量，并使用心脏匀浆来评估心脏炎症（IL - 6、CRP）、心脏毒性（CTnT、LDH、CKMB）和高血压（NO、ACE）标志物。对心脏进行组织病理学检查。阿霉素显著改变心电图，出现高大T波、ST段抬高和宽大QRS波群。结果还显示心脏炎症和高血压生物标志物有显著变化。柚皮素和阿朴色原酮治疗显著减轻了阿霉素对大鼠心电图的影响，降低了心脏炎症和高血压生物标志物的水平。与仅阿霉素组相比，柚皮素和阿朴色原酮治疗组心脏的细胞结构显著改善。本研究表明，柚皮素和阿朴色原酮给药具有心脏保护能力，并且可能由于其抗炎和清除自由基的特性，改善了阿霉素诱导的心脏毒性。
