Rizk Hanan A, Masoud Marwa A, Maher Omar W
Department of Pharmacology, National Organization for Drug Control and Research (NODCAR), Giza, Egypt.
J Biochem Mol Toxicol. 2017 Dec;31(12). doi: 10.1002/jbt.21977. Epub 2017 Aug 16.
Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use cause neurobiological side effects. The aim of the present study was to investigate the prophylactic effect exerted by daily administration of ellagic acid (EA) and rosmarinic acid (RA) on DOX-induced neurotoxicity in rats. Our data showed that DOX-induced significant elevation of brain malondialdehyde, tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), caspase-3, and cholinesterase associated with significant reduction in reduced glutathione, monoamines namely serotonin, dopamine, as well as norepinephrine. Concomitant administration of EA (10 mg/kg/day, p.o. for 14 days) and/or RA (75 mg/kg/day, p.o. for 14 days) with DOX significantly mitigated the neural changes induced by DOX. Meanwhile, treatment ameliorated pro-inflammatory cytokines as TNF-α, iNOS, and attenuated oxidative stress biomarkers as well as brain monoamines. In conclusion, EA and RA can effectively protect against DOX-induced neurotoxicity, and the mechanisms underlying the neuroprotective effect are potentially associated with its antioxidant, anti-inflammatory, and antiapoptotic properties.
阿霉素（DOX）是一种广泛应用于人类恶性肿瘤治疗的化疗药物。长期使用会导致神经生物学副作用。本研究的目的是探讨每日给予鞣花酸（EA）和迷迭香酸（RA）对阿霉素诱导的大鼠神经毒性的预防作用。我们的数据显示，阿霉素会导致脑丙二醛、肿瘤坏死因子-α（TNF-α）、诱导型一氧化氮合酶（iNOS）、半胱天冬酶-3和胆碱酯酶显著升高，同时谷胱甘肽、单胺类物质如血清素、多巴胺以及去甲肾上腺素显著减少。EA（10毫克/千克/天，口服，共14天）和/或RA（75毫克/千克/天，口服，共14天）与阿霉素联合给药可显著减轻阿霉素诱导的神经变化。同时，治疗改善了促炎细胞因子如TNF-α、iNOS，并减轻了氧化应激生物标志物以及脑单胺类物质的变化。总之，EA和RA可有效预防阿霉素诱导的神经毒性，其神经保护作用的潜在机制可能与其抗氧化、抗炎和抗凋亡特性有关。
