Department of Clinical and Hospital Pharmacy, Faculty of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, 30001, Saudi Arabia; Department of Clinical Pharmacy, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566, Egypt.
Department of Pathology, Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, 30001, Saudi Arabia; Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, 32511, Egypt.
Biomed Pharmacother. 2017 Aug;92:519-527. doi: 10.1016/j.biopha.2017.05.103. Epub 2017 May 30.
This study targeted to test the potential protective role of lutein against lung and liver damage associated with cyclophosphamide (CP) administration. Lutein was given orally for 5days at two different doses both before and after CP injection. Results have shown that CP administration caused marked pulmonary and hepatic injurious effects in mice. Lung damage was evident through increased lung wet/dry ratio, elevated inflammatory cells infiltration into the pulmonary tissues, increased total protein content and lactate dehydrogenase (LDH) activity in the broncho-alveolar lavage fluid. Estimation of high levels of serum transaminases, alkaline phosphatase and LDH in serum revealed hepatic injury. Histopathological examination of both organs confirmed the biochemical analysis. Elevation of oxidative stress along with depressed anti-oxidant status of lung and liver were evident in CP-intoxicated animals. Furthermore, CP induced elevation of inflammatory cytokines (NOx, TNF-α, IL-6) contaminant with activation of nuclear factor kappa-B (NF-κB) and p38 mitogen activated protein kinase (p38-MAPK). On the other side, lutein treatment successfully protected the lung and the liver as indicated by improvement of the biochemical and histopathological parameters. These results suggest that lutein can ameliorate CP-induced pulmonary and hepatic oxidative injurious effects via inhibition of reactive oxygen species (ROS)/NF-κB/MAPK pathway.
本研究旨在测试叶黄素对环磷酰胺（CP）给药引起的肺和肝损伤的潜在保护作用。叶黄素在 CP 注射前后 5 天内以两种不同剂量口服给予。结果表明，CP 给药导致小鼠肺部和肝脏出现明显的损伤效应。肺损伤表现为肺湿/干重比增加、炎性细胞浸润肺组织、支气管肺泡灌洗液中总蛋白含量和乳酸脱氢酶（LDH）活性升高。血清中转氨酶、碱性磷酸酶和 LDH 水平升高表明存在肝损伤。对两个器官的组织学检查证实了生化分析的结果。CP 中毒动物的肺和肝氧化应激升高，抗氧化状态降低。此外，CP 诱导的炎性细胞因子（NOx、TNF-α、IL-6）升高，与核因子 kappa-B（NF-κB）和丝裂原活化蛋白激酶 p38（p38-MAPK）的激活有关。另一方面，叶黄素治疗成功地保护了肺和肝脏，表现为生化和组织病理学参数的改善。这些结果表明，叶黄素可以通过抑制活性氧（ROS）/NF-κB/MAPK 途径来减轻 CP 诱导的肺和肝氧化损伤效应。
