Department of Biophysics, Panjab University, Chandigarh, India.
Environ Toxicol. 2019 Jul;34(7):804-813. doi: 10.1002/tox.22747. Epub 2019 Apr 5.
The clinical application of cisplatin (CP), one of the most extensively used antineoplastic drug, is restricted by its numerous side effects. CP's antitumor potential resides in the free generation of reactive oxygen species leading to oxidative stress. This stress is a source of the side effects associated with its use. Ellagic acid (EA), a polyphenol is known to possess multiple health benefits owing to its antioxidant properties. EA is largely metabolized by the colon microbiota of different mammals and therefore was a polyphenol of choice in the present study. The present study was thus carried out to explore the protective potential of EA on CP induced hepatotoxicity in colon tumor bearing mice. The administration of EA (10 mg/kg bwt po daily for 6 weeks) significantly ameliorated the toxicity caused by CP (5 mg/kg bwt ip once a week for 4 weeks). Activities of liver marker enzymes and lactate dehydrogenase were brought back to normal. EA cotreatment also led to a marked reduction in the extent of peroxidative damage to liver tissue as was evident from the improvement in the histopathological changes observed and FT-IR analysis. The present study, therefore, suggests that the administration of EA reduces the CP-induced hepatotoxicity, thereby emerging out as a potential candidate for chemopreventive action.
顺铂(CP)是最广泛使用的抗肿瘤药物之一,其临床应用受到其众多副作用的限制。CP 的抗肿瘤潜力在于自由生成导致氧化应激的活性氧。这种应激是其使用相关副作用的来源。由于具有抗氧化特性,鞣花酸(EA)是一种多酚,已知具有多种健康益处。EA 主要由不同哺乳动物的结肠微生物群代谢,因此在本研究中选择 EA 作为多酚。因此,本研究旨在探索 EA 对 CP 诱导的结肠癌荷瘤小鼠肝毒性的保护潜力。EA(10mg/kg bwt 每天 po,共 6 周)的给药显著改善了 CP(5mg/kg bwt 每周一次 ip,共 4 周)引起的毒性。肝标志物酶和乳酸脱氢酶的活性恢复正常。EA 共同处理还导致肝组织过氧化损伤程度明显降低,从观察到的组织病理学变化改善和 FT-IR 分析中可以明显看出。因此,本研究表明,EA 的给药可降低 CP 诱导的肝毒性,从而成为化学预防作用的潜在候选物。