Beneficial properties of melatonin in an experimental model of pancreatic cancer
Beneficial properties of melatonin in an experimental model of pancreatic cancer
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DOI：
10.1111/j.1600-079x.2007.00472.x
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发表时间：
2007-10-01
影响因子：
10.3
通讯作者：
Padillo, Francisco Javier
中科院分区：
文献类型：
--
作者：
Ruiz-Rabelo, Juan F.;Vazquez, Reyes;Padillo, Francisco Javier
胰腺癌是一个主要的健康问题，因为这种疾病的侵袭性和缺乏有效的系统治疗。褪黑素具有抗氧化活性，可防止实验性遗传毒性。然而，褪黑素在胰腺癌中的作用还没有得到测试。用N-亚硝基二(2-氧丙基)胺(BOP)诱发叙利亚仓鼠胰腺癌。褪黑素在BOP诱导阶段(12wk)和/或在诱导后阶段(12wk)给药。测定胰腺组织中过氧化脂质(LPO)和抗氧化剂(超氧化物歧化酶、过氧化氢酶、还原型谷胱甘肽和谷胱甘肽过氧化物酶)等氧化应激指标。此外，还研究了不典型增生(AH)、高分化腺癌和中分化腺癌(分别为ADC-WD和ADC-MD)的存在。给予BOP后，胰腺组织发生强烈的氧化应激和ADC的诱导。在诱导或诱导后给予褪黑素，可降低LPO，改善抗氧化状态，并显著减少ADC的存在，但仍有部分AH存在。总而言之，褪黑素治疗可以减少BOP引起的胰腺氧化损伤和癌症结节。
Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin has antioxidant activity and prevents experimental genotoxicity. However, the effect of melatonin in pancreatic cancer has not been tested. Pancreatic carcinogenesis was induced by N-nitrosobis (2-oxopropyl)amine (BOP) in Syrian hamsters. Melatonin was administered during the BOP-induction phase (12 wk) and/or following the postinduction phase (12 wk). Different parameters of oxidative stress including lipid peroxides (LPO) and antioxidants (superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase) were determined in pancreatic tissue. Also, the presence of atypical hyperplasia (AH), well and moderately differentiated adenomacarcinoma (ADC-WD and ADC-MD, respectively) were studied. The administration of BOP induced an intense oxidative stress and ADC induction in the pancreas. The administration of melatonin during the induction or postinduction phase reduced LPO and improved the antioxidant status, as well as drastically reducing the presence of ADC but some AH remained. In conclusion, treatment with melatonin reduced oxidative damage and cancer nodules induced by BOP in the pancreas.