Dziegiel Piotr, Murawska-Ciałowicz Eugenia, Jethon Zbigniew, Januszewska Lidia, Podhorska-Okołów Marzena, Surowiak Paweł, Zawadzki Marcin, Rabczyński Jerzy, Zabel Maciej
Department of Histology and Embryology, Wrocław Medical University, Wrocław, Poland.
J Pineal Res. 2003 Oct;35(3):183-7. doi: 10.1034/j.1600-079x.2003.00079.x.
The study aimed at determining the effect of melatonin on the activity of protective antioxidative enzymes in the heart and of lipid peroxidation products in the course of intoxication with doxorubicin (DOX). The rats were categorized into four groups, receiving: 0.9% NaCl i.p. (NaCl control); melatonin [20 mg/kg body weight (b.w.)] s.c. (control Mel); DOX (2.5 mg/kg b.w.) i.p.; melatonin plus DOX in doses as above. All the substances were administered once in a week for four consecutive weeks. Homogenates of heart tissue were examined for activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), levels of reduced glutathione (GSH) and of lipid peroxidation indices (MDA + 4-HDA). Administration of melatonin alone did not induce alterations in levels of MDA + 4-HDA, GSH, or in activity of GPx, SOD or CAT, as compared to the group receiving 0.9% NaCl. GSH levels decreased following DOX but remained at normal levels following DOX and melatonin. The level of MDA + 4-HDA increased following DOX, as compared with the control, a change prevented by the combination of DOX + melatonin. Activities of GPx, SOD and CAT were higher in groups receiving DOX and/or DOX plus melatonin than in control groups. Activity of CAT and the level of GSH in the group receiving DOX plus melatonin were significantly higher than in the group intoxicated with DOX alone. The obtained results demonstrate that, when given in parallel with DOX, melatonin protects cardiomyocytes from damaging effects of the cytostatic drug (reflected by the levels of MDA + 4-HDA). The protective effect resulted, in part from the augmented levels of GSH and from stimulation of CAT activity by melatonin in cardiomyocytes subjected to the action of DOX.
本研究旨在确定褪黑素对阿霉素（DOX）中毒过程中心脏保护性抗氧化酶活性及脂质过氧化产物的影响。将大鼠分为四组，分别接受：腹腔注射0.9%氯化钠（NaCl对照组）；皮下注射褪黑素[20mg/kg体重（b.w.）]（褪黑素对照组）；腹腔注射DOX（2.5mg/kg b.w.）；上述剂量的褪黑素加DOX。所有物质均连续四周每周给药一次。检测心脏组织匀浆中谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）的活性，还原型谷胱甘肽（GSH）水平及脂质过氧化指标（MDA + 4 - HDA）。与接受0.9%氯化钠的组相比，单独给予褪黑素未引起MDA + 4 - HDA、GSH水平或GPx、SOD、CAT活性的改变。DOX给药后GSH水平下降，但DOX和褪黑素联合给药后GSH水平维持在正常水平。与对照组相比，DOX给药后MDA + 4 - HDA水平升高，DOX与褪黑素联合使用可防止这种变化。接受DOX和/或DOX加褪黑素的组中，GPx、SOD和CAT的活性高于对照组。接受DOX加褪黑素组的CAT活性和GSH水平显著高于单独DOX中毒组。所得结果表明，与DOX同时给予时，褪黑素可保护心肌细胞免受细胞毒性药物的损伤作用（由MDA + 4 - HDA水平反映）。这种保护作用部分源于GSH水平的升高以及褪黑素对受DOX作用的心肌细胞中CAT活性的刺激。
