Department of Zoology and Animal Physiology, Institute of Biology and Environment Protection, Faculty of Science, Pomeranian University of Slupsk, Słupsk, Poland.
Department of Animal Physiology, Institute of Biology and Ecology, Pavol Jozef Šafárik University, Košice, Slovakia.
Adv Exp Med Biol. 2018;1047:7-19. doi: 10.1007/5584_2017_128.
The aim of this study was to determine the effects of long-term administration of the oral antidiabetic metformin or the pineal hormone melatonin, and a combination thereof, in preventing oxidative stress in the heart tissue of female Sprague-Dawley rats with mammary tumors induced by N-methyl-N-nitrosourea (NMU) (50 mg/kg) given on the 42nd postnatal day. Metformin and melatonin were administered 12 days before and 16 weeks after the carcinogen. During the experiment, all animals were fed a high fat diet (10% total fat, 2.5% from lard, and 7.5% from palm oil). The findings are that mammary carcinogenesis generated oxidative stress. Reactive oxygen species (ROS) content, estimated from thiobarbituric acid reactive substances (TBARS), oxidatively modified protein content (aldehyde and ketone derivatives), and the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, and glutathione peroxidase were all augmented. Metformin caused a decrease in oxidative stress in the heart, accompanied by a decrease in diene conjugates, the elimination of ROS (stable total antioxidant status), and the activation of catalase and glutathione reductase. Melatonin caused an increase in total antioxidant status and a substantial reduction in ROS as estimated from aldehyde and ketone derivatives, lipid peroxidation at the initial (diene conjugates) and terminal stages (TBARS), and increased catalase and glutathione peroxidase activities. Metformin and melatonin combined reversed the effects of NMU on oxidative stress. In conclusion, melatonin reduces the level of oxidative stress in the heart tissue, caused by NMU carcinogenesis and a high fat diet, significantly stronger than metformin.
本研究旨在确定长期给予口服抗糖尿病药物二甲双胍或松果体激素褪黑素，以及两者联合应用，对 N-甲基-N-亚硝脲（NMU）（50mg/kg）诱导的乳腺肿瘤雌性 Sprague-Dawley 大鼠心脏组织氧化应激的预防作用。二甲双胍和褪黑素在致癌剂给予后第 42 天前 12 天和 16 周后给予。在实验过程中，所有动物均给予高脂肪饮食（总脂肪 10%，猪油 2.5%，棕榈油 7.5%）。研究结果表明，乳腺致癌作用产生氧化应激。丙二醛反应物质（TBARS）估算的活性氧（ROS）含量、氧化修饰蛋白含量（醛和酮衍生物）以及抗氧化酶超氧化物歧化酶、谷胱甘肽还原酶和谷胱甘肽过氧化物酶的活性均增加。二甲双胍降低了心脏的氧化应激，伴随着二烯共轭物的减少、ROS 的消除（稳定的总抗氧化状态）以及过氧化氢酶和谷胱甘肽还原酶的激活。褪黑素引起总抗氧化状态的增加和 ROS 的大量减少，这是通过醛和酮衍生物、初始（二烯共轭物）和终末阶段（TBARS）的脂质过氧化以及过氧化氢酶和谷胱甘肽过氧化物酶活性的增加来估计的。二甲双胍和褪黑素联合应用逆转了 NMU 对氧化应激的影响。综上所述，褪黑素降低了 NMU 致癌作用和高脂肪饮食引起的心脏组织氧化应激水平，作用明显强于二甲双胍。
