Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Health Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Aug;391(8):819-832. doi: 10.1007/s00210-018-1506-4. Epub 2018 May 7.
Despite their clinical benefits in cancer treatment, the deleterious effects on heart following chemo/radiotherapy are of increasing importance. Zingerone, a natural polyphenol, possesses multiple biological activities, such as antioxidant and anti-inflammatory. Thus, the current study was designed to assess the potential cardioprotective effects of zingerone against cisplatin or γ-radiation. Zingerone was given by intragastric intubation (25 mg/kg) daily for three successive weeks prior to the induction of cardiotoxicity using a single dose of cisplatin (20 mg/kg, i.p.) or a whole body γ-irradiation at a single dose of 6 Gy. Zingerone pre-treatment significantly reduced the abnormalities in heart histology and the increase in the cardiotoxicity indices, serum lactate dehydrogenase, and creatine kinase-MB activities, as well as plasma cardiac troponin T and B-natriuretic peptide, induced by cisplatin or γ-radiation. Further, zingerone, except for superoxide dismutase, notably ameliorated the state of oxidative stress as evidenced by a significant decrease in malondialdehyde level accompanied with a significant increase in the reduced glutathione content and catalase activity. Additionally, zingerone mitigated the increase in the inflammatory markers including serum level of tumor necrosis factor-alpha, cardiac myeloperoxidase activity, and cyclooxygenase-2 protein expression. Moreover, zingerone alleviated the elevation of caspase-3 gene expression and the prominent nuclear DNA fragmentation and attenuated the decrease in mitochondrial complexes' activities. This study sheds the light on a probable protective role of zingerone as an antioxidant, anti-inflammatory, and antiapoptotic agent against cisplatin- or γ-radiation-induced cardiotoxicity and holds a potential in regard to therapeutic intervention for chemo/radiotherapy mediated cardiac damage.
尽管在癌症治疗中有临床益处，但化疗/放疗后对心脏的有害影响越来越受到重视。姜酮是一种天然多酚，具有多种生物学活性，如抗氧化和抗炎作用。因此，本研究旨在评估姜酮对顺铂或γ辐射引起的心脏毒性的潜在保护作用。在使用顺铂（20mg/kg，腹腔注射）单次剂量或全身γ照射（单次剂量 6Gy）诱导心脏毒性之前，通过灌胃给予姜酮（25mg/kg），每天连续 3 周。姜酮预处理可显著减轻顺铂或γ辐射引起的心脏组织学异常和心脏毒性指标升高、血清乳酸脱氢酶和肌酸激酶-MB 活性升高以及血浆心肌肌钙蛋白 T 和 B 型利钠肽升高。此外，姜酮除了超氧化物歧化酶外，还显著改善了氧化应激状态，表现为丙二醛水平显著降低，同时还原型谷胱甘肽含量和过氧化氢酶活性显著增加。此外，姜酮减轻了炎症标志物的增加，包括血清肿瘤坏死因子-α水平、心肌髓过氧化物酶活性和环氧化酶-2 蛋白表达。此外，姜酮减轻了 caspase-3 基因表达的升高和明显的核 DNA 片段化，并减轻了线粒体复合物活性的降低。这项研究揭示了姜酮作为抗氧化剂、抗炎剂和抗细胞凋亡剂在预防顺铂或 γ 辐射引起的心脏毒性方面的可能保护作用，并为化疗/放疗介导的心脏损伤的治疗干预提供了潜力。
