Institute of Biomedicine, University of Bergen, Bergen, Norway.
Cell Biochem Funct. 2011 Jul;29(5):356-64. doi: 10.1002/cbf.1756. Epub 2011 May 16.
Strong anti-neoplastic anthracyclines like daunorubicin (DNR) and doxorubicin (DOX) have high efficacy against systemic neoplasm and solid tumours. However, clinically, they cause chronic cardiomyopathy and congestive heart failure. Red palm oil (RPO) supplementation can protect the heart against ischemic injury. We therefore hypothesize that supplementation with RPO during chemotherapy may protect the heart. Control rats received a standard diet, and the experimental group received RPO in addition for 4 weeks. Each group was subsequently injected with either saline or DNR over a 12-day period towards the end of 4 weeks. Hearts were excised and perfused on a working heart system. Functional parameters were measured. Tissue samples were collected for analysis of mRNA and protein levels. DNR + RPO increased aortic output by 25% (p < 0.05) compared with DNR only. Furthermore, DNR treatment significantly reduced tissue mRNA levels of superoxide dismutase 1 (SOD1) and nitric oxide synthase 1 (NOS1) compared with untreated controls. Protein expression of SOD1 followed the same pattern as mRNA levels. NOS1 protein levels were significantly increased in DNR treated rats when compared with untreated controls. In addition, DNR increased phosphorylation of p38 and Jun N-terminal kinase compared with untreated controls, whereas DNR + RPO completely counteracted this activation. DNR + RPO significantly up regulated the protein extracellular signal-regulated kinase 1 level compared with DNR only. In this model of DNR treatment, RPO is associated with stabilization of important antioxidant enzymes such NOS and SOD, and inhibition of the 'stress' induced mitogen-activated protein kinase pathways. Dietary RPO also maintained function, similar to control, in DNR treated hearts.
强抗肿瘤蒽环类药物,如柔红霉素(DNR)和阿霉素(DOX),对全身肿瘤和实体瘤具有高效。然而,临床上,它们会导致慢性心肌病和充血性心力衰竭。红棕榈油(RPO)补充剂可以保护心脏免受缺血损伤。因此,我们假设在化疗期间补充 RPO 可能会保护心脏。对照组大鼠接受标准饮食,实验组大鼠在接受标准饮食的同时额外补充 RPO 4 周。每组大鼠在第 4 周末结束时连续 12 天分别注射生理盐水或 DNR。取出心脏并在工作心脏系统上进行灌注。测量功能参数。收集组织样本进行 mRNA 和蛋白质水平分析。与仅接受 DNR 的大鼠相比,DNR + RPO 使主动脉输出增加了 25%(p < 0.05)。此外,与未经处理的对照组相比,DNR 处理显著降低了组织中超氧化物歧化酶 1(SOD1)和一氧化氮合酶 1(NOS1)的 mRNA 水平。SOD1 的蛋白表达模式与 mRNA 水平相同。与未经处理的对照组相比,DNR 处理的大鼠中 NOS1 蛋白水平显著增加。此外,与未经处理的对照组相比,DNR 增加了 p38 和 Jun N-末端激酶的磷酸化,而 DNR + RPO 完全阻止了这种激活。与仅接受 DNR 的大鼠相比,DNR + RPO 显著上调了细胞外信号调节激酶 1 蛋白水平。在 DNR 治疗的这种模型中,RPO 与重要抗氧化酶如 NOS 和 SOD 的稳定有关,并抑制“应激”诱导的丝裂原激活蛋白激酶途径。膳食 RPO 还维持了 DNR 处理的心脏的功能,类似于对照组。