Shokrzadeh M, Chabra A, Naghshvar F, Ahmadi A, Jafarinejhad M, Hasani-Nourian Y
Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Drug Res (Stuttg). 2015 Jun;65(6):281-6. doi: 10.1055/s-0034-1371801. Epub 2014 Mar 25.
This study was undertaken to evaluate the protective effects of melatonin against cyclophosphamide (CP)-induced oxidative lung toxicity in mice. Mice were pre-treated with various doses of melatonin for 7 consecutive days and were then injected with CP (200 mg/kg b. w.) 1 h after last melatonin injection. After 24 h, the mice were euthanized and their lungs were immediately harvested. Several biomarkers associated with oxidative stress in lung homogenates, such as thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH) levels and the activity of superoxide dismutase (SOD) and catalase (CAT) were measured spectrophotometrically. A single dose of CP markedly altered the levels of these oxidative stress biomarkers in lung homogenates. However, increased lipid peroxidation, measured as TBARs, was significantly inhibited in the lung tissues of the melatonin-pretreated mice compared to the CP alone-injected group. In addition, pretreatment with melatonin also significantly restored GSH levels and SOD and CAT activities. Melatonin also effectively protected animals from CP-induced histological abnormalities in lung tissue. In conclusion, the increase in oxidative stress markers and concomitant adaptations by the antioxidant defense system indicates that oxidative stress plays an important role in CP-induced damage to the lung. Moreover, melatonin is a potent natural antioxidant that helps prevent CP-induced oxidative toxicity in mouse lung tissues. Thus, because melatonin is regarded to be a safe pineal secretory product, it may be used concomitantly as a supplement to reduce lung damage in patients undergoing chemotherapy.
本研究旨在评估褪黑素对环磷酰胺（CP）诱导的小鼠肺氧化毒性的保护作用。小鼠连续7天接受不同剂量的褪黑素预处理，然后在最后一次注射褪黑素1小时后注射CP（200mg/kg体重）。24小时后，对小鼠实施安乐死并立即摘取其肺脏。采用分光光度法测定肺匀浆中与氧化应激相关的几种生物标志物，如硫代巴比妥酸反应性物质（TBARs）、还原型谷胱甘肽（GSH）水平以及超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。单剂量的CP显著改变了肺匀浆中这些氧化应激生物标志物的水平。然而，与单独注射CP的组相比，褪黑素预处理小鼠肺组织中以TBARs衡量的脂质过氧化增加受到了显著抑制。此外，褪黑素预处理还显著恢复了GSH水平以及SOD和CAT的活性。褪黑素还有效保护动物免受CP诱导的肺组织组织学异常。总之，氧化应激标志物的增加以及抗氧化防御系统的相应适应表明氧化应激在CP诱导的肺损伤中起重要作用。此外，褪黑素是一种有效的天然抗氧化剂，有助于预防CP诱导的小鼠肺组织氧化毒性。因此，由于褪黑素被认为是一种安全的松果体分泌产物，它可作为一种补充剂同时使用，以减少接受化疗患者的肺损伤。
