Salah Rania, El-Sayed Gehad, El-Sherbini El-Said, El-Adl Mohamed
Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Delta University for Science and Technology, Mansoura, Egypt.
Open Vet J. 2025 May;15(5):2218-2229. doi: 10.5455/OVJ.2025.v15.i5.39. Epub 2025 May 31.
Cyclophosphamide (CP) is known to cause pulmonary injury through free radical production and proinflammatory cytokines activation. Lung damage is associated with significant mortality, primarily due to the development of severe inflammation and pulmonary edema. On the other hand, citicoline, a key intermediate in the phosphatidylcholine biosynthesis pathway, has neurovascular protective and reparative properties. Numerous studies have highlighted the potential antioxidant and antiinflammatory effects of this agent in the context of various pathological conditions.
Our study aimed to explore the potential protective effects of citicoline against oxidative stress, inflammation, and tissue damage caused by CP in an experimental model.
Rats were given 200 mg/kg of CP as a single dose, either alone or in combination with citicoline (500 or 250 mg/kg), administered orally once daily for 14 days, beginning 7 days prior to CP administration. On the final day of the experiment, all animals were euthanized, and lung tissues were collected for further analysis.
CP administration led to a significant elevation in the lung-to-body weight ratio, inflammatory cell infiltration, and elevated levels of lactate dehydrogenase, total protein, nuclear factor kappa B, Interleukin-1β, NOD-like receptor protein 3, and caspase-1 in bronchoalveolar lavage fluid. Furthermore, CP treatment increased the concentrations of malondialdehyde and nitrate/nitrite and reduced glutathione levels in the lungs. Additionally, mRNA of Interleukin 6 and tumor necrosis factor-α levels were significantly elevated. These biochemical alterations were corroborated by histopathological findings, which revealed significant lung tissue damage. However, treatment with citicoline significantly reduced the pulmonary pathological changes induced by CP.
These findings imply that citicoline's antiinflammatory and antioxidant properties provide protection against CP-induced lung damage.
已知环磷酰胺（CP）通过产生自由基和激活促炎细胞因子导致肺损伤。肺损伤与显著的死亡率相关，主要是由于严重炎症和肺水肿的发展。另一方面，胞磷胆碱是磷脂酰胆碱生物合成途径中的关键中间体，具有神经血管保护和修复特性。众多研究强调了该药物在各种病理状况下的潜在抗氧化和抗炎作用。
我们的研究旨在探讨在实验模型中胞磷胆碱对CP引起的氧化应激、炎症和组织损伤的潜在保护作用。
大鼠以200mg/kg的剂量单次给予CP，单独给药或与胞磷胆碱（500或250mg/kg）联合给药，从给予CP前7天开始，每天口服给药一次，持续14天。在实验的最后一天，所有动物被安乐死，并收集肺组织进行进一步分析。
给予CP导致肺与体重比显著升高、炎症细胞浸润，以及支气管肺泡灌洗液中乳酸脱氢酶、总蛋白、核因子κB、白细胞介素-1β、NOD样受体蛋白3和半胱天冬酶-1水平升高。此外，CP处理增加了肺中丙二醛和硝酸盐/亚硝酸盐的浓度，并降低了谷胱甘肽水平。另外，白细胞介素6和肿瘤坏死因子-α的mRNA水平显著升高。这些生化改变得到了组织病理学结果的证实，该结果显示肺组织有显著损伤。然而，胞磷胆碱治疗显著减轻了CP诱导的肺部病理变化。
这些发现表明胞磷胆碱的抗炎和抗氧化特性可保护机体免受CP诱导的肺损伤。
