Ristić Lidija, Rančić Milan, Radović Milan, Krtinić Dane, Pavlović Milorad, Ilić Bojan, Milojković Miloš, Živković Nikola, Turković Ksenija, Sokolović Dušan
Department for Internal Medicine, Faculty of Medicine, University of Niš, Niš, Serbia.
Clinic for Lung Diseases, Clinical Center Niš, Niš, Serbia.
Arch Med Sci. 2020 Jun 12;20(3):977-983. doi: 10.5114/aoms.2020.95952. eCollection 2024.
Cisplatin is one of the most frequently used chemotherapeutics, which is known to cause both tumor and normal lung tissue damage through the generation of free radicals and cells apoptosis/necrosis. Melatonin is a neurohormone that regulates numerous physiological processes in the body both through receptor pathways and by maintaining tissue redox homeostasis.
The extent of rat lung damage induced by cisplatin and the effects of melatonin on this process was determined based on the pathohistological changes and biochemical disturbances in tissue lipid peroxidation, protein carbonyl modification and in the activity of xanthine oxidase (XO), caspase-3 and DNases.
Histopathological analysis of rat lung tissue obtained from animals that received cisplatin found them to be edematous, with significant deterioration of alveolar epithelium. These morphological changes are accompanied by a significant increase in all studied oxidative stress-related parameters, as well as with the activity of apoptosis-related enzymes. A five-day treatment with melatonin completely prevented a cisplatin-induced increase in oxidative stress-related parameters and in the activity of XO, caspase-3 and alkaline DNase. Also, the histopathological changes observed during microscopic analysis were much less pronounced than in the group that received cisplatin only.
These results can potentially be connected with the ability of melatonin to inhibit the activity of XO, caspase-3 and alkaline DNase and/or its ability to scavenge free radicals, thus preventing lung damage induced by cisplatin.
顺铂是最常用的化疗药物之一，已知它会通过产生自由基以及细胞凋亡/坏死来导致肿瘤和正常肺组织损伤。褪黑素是一种神经激素，它通过受体途径以及维持组织氧化还原稳态来调节身体中的众多生理过程。
基于组织脂质过氧化、蛋白质羰基修饰以及黄嘌呤氧化酶（XO）、半胱天冬酶-3和脱氧核糖核酸酶的活性方面的病理组织学变化和生化紊乱，来确定顺铂诱导的大鼠肺损伤程度以及褪黑素对这一过程的影响。
对接受顺铂的动物所获得的大鼠肺组织进行组织病理学分析发现，这些组织出现水肿，肺泡上皮显著恶化。这些形态学变化伴随着所有研究的氧化应激相关参数以及凋亡相关酶的活性显著增加。用褪黑素进行为期五天的治疗完全阻止了顺铂诱导的氧化应激相关参数以及XO、半胱天冬酶-3和碱性脱氧核糖核酸酶活性的增加。此外，显微镜分析期间观察到的组织病理学变化比仅接受顺铂的组要明显轻得多。
这些结果可能与褪黑素抑制XO、半胱天冬酶-3和碱性脱氧核糖核酸酶活性的能力和/或其清除自由基的能力有关，从而预防顺铂诱导的肺损伤。
